Gene therapy has traditionally been applied to well-understood diseases where a single genetic mutation was to blame. A new generation of technology is expanding the potential of gene therapy to treat conditions that were previously unreachable.

Since the first gene therapy clinical trials in the 1990s, the technology has made its way into the market for conditions ranging from blindness to cancer.

Gene therapy has the potential to fix any genetic mutation causing disease by inserting a new copy of the faulty gene. However, its reach has historically been limited.

Weve been constrained with the things we can do with gene therapy, said Dmitry Kuzmin, Managing Partner at 4BIO Capital, a London-based VC that specifically invests in advanced therapies. If you look across the successes in gene therapy in the last five years, most of these were in diseases that are pretty straightforward from the engineering perspective.

Technical limitations have meant that gene therapy has been restricted to rare diseases caused by a single genetic mutation, as well as to certain areas of the body, such as the eye and the liver.

According to Kuzmin, there have been so far three generations of gene therapy technology. Generation one would be classic single-gene replacement, such as Luxturna, a gene therapy to fix a specific genetic mutation causing blindness. Generation two would consist of using gene therapy to introduce new functions. An example is Kymriah, where immune cells are equipped with a molecule that helps them hunt down cancer cells.

The third generation is the one that could hold the key to unlocking the full potential of gene therapy. It englobes several technologies that can be used to introduce a new drug target into the patient, making it possible to turn the therapy on and off as well as to tune its intensity.

As the first two generations get optimized and the third generation enters the clinic, we are now expanding our reach into areas that have been previously rather inaccessible, Kuzmin told me. One of them is the brain.

Treating the brain has long been a huge challenge for medicine. Take epilepsy, for example.

Epilepsy affects 1% of the whole population and about 30% of people with seizures of epilepsy continue to have seizures despite medication, said Dimitry Kullmann, Professor at University College London. Theres a paradox. We have a good understanding of the mechanisms behind epilepsy, but were unable to suppress seizures in a significant proportion of people with epilepsy.

The reason is that the molecules that we use for drugs dont target the epileptic zone of the brain; they bathe the entire body with medication, Kullmann told me. These drugs dont differentiate between neurons and synapses that derive the seizures, and those parts of the brain that are responsible for memory, sensory functions, motor functions and balance.

Gene therapy could provide a solution for this problem. Kullmanns group has been researching this approach for years and is now getting ready to start the first clinical trial in humans within a year.

A gene therapy can be directly injected in the area of the brain causing seizures. Furthermore, using DNA sequences called promoters, it is possible to restrict the effect of gene therapy to specific neurons within that area. In the case of epilepsy, gene therapy can be used to decrease the activity of only excitatory neurons, which cause epileptic seizures when they are overactive.

Another approach that Kullmans group is testing is chemogenetics. The idea here is to use gene therapy to put a specific receptor into the neurons, explained Kullmann. This receptor is designed to respond to a drug that, when given to the patient, decreases the activity of the neuron to suppress seizures.

The advantage is that you can switch on and off the therapeutic effect on demand by just giving, or not giving the drug, Kullmann said. This approach can thus make gene therapy more precise, being able to tune it to the specific needs of each patient. In addition, it reduces the big challenge of getting the dose right in a one-off treatment.

Ultimately, this technology could allow scientists to target a wide range of conditions that come under the umbrella of epilepsy, rather than just a specific form of the condition caused by a genetic mutation.

The approach could be extended to other conditions involving the brain, such as Parkinsons, ALS and pain. However, this kind of research is still at an early stage and it will take a while until its potential is proven in humans.

Blindness has been a major target of gene therapy because of the fact that the eye is an ideal target for this technology. The activity of the immune system is suppressed in the eye, minimizing the chances of rejection. In addition, unlike other cells in the body, those involved in vision are not renewed over time, being able to retain the injected DNA for years.

However, there are hundreds of genetic mutations that can cause blindness. With the classical gene therapy approach, a different therapy would have to be developed from scratch for each mutation. While some companies are doing just this for the most common mutations causing blindness, many other less frequent mutations are being left behind.

Others are turning to new generations of gene therapy technology. We figured out that it would be very, very difficult to use the classical gene therapy approach in each individual mutation, said Bernard Gilly, CEO of GenSight, a Parisian biotech developing gene therapies for blindness.

While the companys leading programs follow this classical approach, the company has also started clinical trials using a technology called optogenetics. Following a similar principle to gene therapy, optogenetics consists of introducing a protein that reacts to light into a cell.

GenSight is using optogenetics to develop a single therapy for the treatment of retinitis pigmentosa. This genetic condition can be caused by mutations in any of over 200 genes and results in progressive vision loss in children due to the degeneration of photoreceptor cells that perceive light and send signals to the brain.

With optogenetics, it would be possible to transfer the lost photoreceptor function to the cells in the retina that are responsible for relaying visual information to the brain. Using specialized goggles, the images captured by a camera are transformed into light patterns that stimulate these cells in the precise way needed for the brain to form images.

The company is currently testing this approach in clinical trials. We believe that this approach will allow us to restore vision in those patients who became blind because of retinitis pigmentosa, Gilly told me.

Optogenetics would not work a miracle, but it might be able to give people back the ability to navigate an unknown environment with a certain level of autonomy. Recognizing faces is a more challenging goal; although reading is not yet on the horizon, according to Gilly.

Still, the potential of optogenetics to address multiple genetic mutations with a single treatment might be revolutionary. As long as the neurons responsible for sending light signals to the brain are intact, this approach could be extended to other forms of blindness. In addition, conditions affecting the brain such as epilepsy, Parkinsons or ALS could be treated with this approach by introducing an implant to shine light on the target neurons.

However, approaches applying optogenetics to the brain are still further down the line. While optogenetics technology has been around for over 20 years, its application in humans is still very limited and in the early stages of research.

Chemogenetics and optogenetics are just two out of a wave of new technologies addressing the historical limitations of gene therapy. Other approaches are in development, such as using thermogenetics, which consists of introducing proteins that are activated by the heat created by infrared light.

With a growing range of tools available, it is becoming easier than ever for scientists to develop gene therapies that can address the specific challenges of different conditions affecting areas of the body. Traditionally, locations such as the heart, the lungs or the pancreas have been particularly difficult to target with gene therapy. That might soon stop being the case.

As we go forward, were interested in taking gene therapy out of this little box and trying to use all the knowledge we have to benefit patients in larger indications, said Kuzmin.

As gene therapy expands into more mainstream conditions, it could take precision medicine to a whole new level and help address the big variability that is often seen across patients with the same diagnosis.

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How Gene Therapy Is Evolving to Tackle Complex... - Labiotech.eu

Dive Brief:

Lonza is betting big on the future of gene and cell therapy and trying to offer customers an end-to-end solution to meet the complex challenges that come with the field.

Every stage of cell therapy, from patient apheresis through transport, genetic engineering and reinfusion comes with critical requirements for temperature control, speed and chain of identity.

Cryoport operates in more than 100 countries and supports more than 413 clinical trials. Notably, the company also supports three approved therapies: Gilead's Yescarta(axicabtagene ciloleucel), Novartis' Kymriah(tisagenlecleucel) and Bluebird bio's Zynteglo.

Demand for specialized manufacturing and distribution services is growing as researchers figure out new ways to manipulate cells so they can fight cancer and other diseases, Cryoport CEO Jerrell Shelton said in the statement.Cryoport's temperature-controlled supply chain systems fit well with Lonza's manufacturing services, he added.

For Lonza, cell and gene therapies are a new focus, part of a broader turn to the pharmaceutical side of the contract manufacturer's business.

In April 2018, the Swiss CDMO opened the doors to a 300,000 square-foot plant in Texas dedicated to producing the complex treatments.

CEO Marc Funk told BioPharma Dive in an interview earlier this year that Lonza has now worked with over 45 customers seeking supply of viral vectors, which are used to deliver gene therapies.

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Lonza taps Cryoport to bolster cell and gene therapy delivery - BioPharma Dive

Gene therapies offer a "world of wonders" for patients, but with some 10,000 of the pricey therapies in development, pharma companies and payers need to get outcomes-based payments nailed down, a top Pfizer exec told Bloomberg.

What's more, Pfizer biopharma president Angela HwangtoldBloomberg's Cynthia Koons, gene therapies present some unique scientific and manufacturing challenges.

Gene therapies currently target monogenic diseases, or diseases that are characterized by a single genetic mutation, Hwang said. There are about 3,000 such disorders, and they're all considered rare diseases. Pfizer itself has three gene therapies in development for hemophilia A, hemophilia B and Duchenne muscular dystrophy.

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Overall, there are 10,000 gene therapy programs in development,Hwang said. If 10% of them end up working,you start to see that potentially gene therapy can become a mainstaytherapyin how we manage diseases," she said in the Bloomberg interview.

That necessitates the key question about payment.Currently, payment systems are centered on paying for individual drug doses. Hwang said the industry needs to get outcomes-based payments worked out, adding that the process could become easier as science advances and data collection improves.

RELATED:Pfizer amps up gene therapy manufacturing with another North Carolina facility

Looking ahead, new gene therapy launches will necessarily drive us to come up with different solutions other than the ones we have today, Hwang said in the interview, referencingsubscription-based payments as one option.Her company is already brainstorming with payers, she added.

There are just two launched U.S. gene therapiesNovartis'Zolgensmaand Spark Therapeutics' Luxturna. Roche is in the process of acquiring Spark, but the buyout has been held up by antitrust regulators.

With already approved gene therapies, the market is adapting. Novartis has offered to allow payers to fund its spinal muscular atrophy gene therapyZolgensmawhich costs $2.125 millionover a period of five years. Thedrugmakerhas also proposed pay-for-performance deals.

Bluebird bio recently won European approval for itsbeta-thalassaemiagene therapyZyntegloand is allowing payers to pay for the drug over several yearsas long asthe med continues to workfor patients.

For its part, Pfizer is buildinga gene therapy manufacturing plant in North Carolina to manufacture clinical trial supplies and potential commercial products following approvals.

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Pfizer's 'brainstorming' payment deals as gene therapies advance, exec tells Bloomberg - FiercePharma

On 19 November, the UK BioBeat19 summit goes to Stevenage to discuss the potential of cell and gene therapy and how to accelerate these transformational medicines.

Victoria Higgins of GSK and Miranda Weston-Smith from BioBeat spoke to two panellists who gave a sneak peek of their remarks and agree wholeheartedly that the discovery side and clinical side work best when they are teamed up.

Sophie Papa, an oncologist at Guys Cancer at Guys and St Thomas NHS Trust, and Aisha Hasan, a clinical development lead at GSK, both recognise the big challenge ahead for cell therapy researchers: to dial up efficacy and dial down toxicity.

Cell and gene therapies, with their remarkable potential to transform medicine, have seen some important but hard-won milestones: it took 20 years of combined academic and industry research to deliver the first gene therapy approval in 2016 and today there are two CAR-Ts approved for haematological malignancies.

Whilst CAR-Ts recognise proteins expressed on the tumour cell surface, making them ideal for targeting blood cancers, more complicated but with greater potential to address solid tumours are the gene modified TCR-T technologies.

These harness the power of T cells to specifically target and destroy tumours even on the inside of cells. TCR-Ts come with an additional level of complexity, but potentially open the door to a range of untreatable cancer types.

Looking at the TCR opportunity is where Sophie Papa sees the inherent trade-off between risk and benefit as an academic clinician whos now evaluating modified T-cell based therapies in clinical trials.

Sophie urges her peers to take courage. It is important to be brave and tolerant of certain toxicities. Academic clinicians and drug researchers need to work closely together to engage the regulators in early discussion, so that we can move cell therapies earlier in treatment schedules as soon as feasible.

Timing is critical to enable patients to be treated when they are physically fit so they can better tolerate these complex and potentially toxic treatments.

From her perspective, this is not an either/or, but an area where discussion and open dialogue will allow us to make the most of the opportunity. By allowing clinical academics to play a lead role in developing guidelines to manage patient safety, we can address legitimate concerns but not let them stand in the way of clinical development, she says.

Aisha brings the perspective of drug discovery and development and starts by asking what is in the realm of the possible from a design perspective.

She says: A superior T-cell therapy will require engineering approaches that enhance efficacy on one-end while also incorporating switches to minimise toxicity.

For example, in a counter-intuitive way, a T-cell with high-killing capacity actually can create dangerous levels of inflammation in the body, due to the rapid death of cancer cells. But the beauty of drug design opens up options:By building a switch within the engineered T-cells, researchers can inactivate the T-cells and prevent harm to the patient, says Aisha.

But this creative problem solving requires open dialogue between clinicians and pharma. Aisha says: The more we talk about clinical need and toxicity benchmarks, the more sophisticated we can be when developing the next generation of enhanced engineered cell therapies.

Theres no doubt that the challenges of delivering cell and gene therapy span the full spectrum of issues related to medicine development. However, the potential for both curative therapy and commercial opportunity is tremendous.

The scientific, clinical, technical, regulatory and commercial challenges are all surmountable when everyone in the ecosystem work together towards a shared goal, united by an unwavering focus on the patient.

Sophie and Aisha are speaking about the translational journey from science to bedside at the BioBeat19 summit.

The BioBeat19 summit on Accelerating cell and gene therapy, 1-6pm, Tuesday 19 November, GSK Stevenage. Guarantee your place by registering at http://www.biobeat19.org

Read more:

Next generation cell and gene therapies: fine tuning the promise - Business Weekly

Across 2019, Vertex has struck deals intended to yield a new generation of breakthrough medicines.

In June, Vertex agreed to pay $245m (220m) upfront to acquire Exonics Therapeutics for its gene editing technology and pipeline of programs targeting diseases including Duchenne muscular dystrophy (DMD). Months later, Vertex put up another $950m to buy Semma Therapeutics and its cell therapy treatment for type I diabetes.

The acquisitions moved Vertex, which started out in small molecules, into new areas, and building out capabilities in those areas will cost money.

In recent years, Vertex has grown its annual operating expenses by 10% to 14%. Talking on a recent quarterly results conference call, Vertex CFO Charles Wagner warned investors to expect costs to rise faster in 2020.

Wagner said, Our current expectation is that the rate of growth will be somewhat higher in 2020 as we invest in research and preclinical manufacturing for selling genetic therapies in support of our programs in type I diabetes, DMD and other diseases.

The move into type I diabetes also takes Vertex into territory that, to some observers, looks different than the areas the company has targeted historically.

Asked by an analyst about the shift in focus, Vertex CEO Jeff Leiden downplayed the differences, noting that type I diabetes is treated in the US in a relatively small number ofcenters that can be targeted by a speciality sales force.

Researchers have achieved positive, long-term outcomes by transplanting cadaveric islets into patients but two barriers have stopped companies from industrialising that approach.

Firstly, there are too few cadaveric islets to treat all type I diabetics. Secondly, immunosuppression is needed to stop patients from rejecting the transplanted cells.

Semma is trying to tackle the problems by differentiating stem cells and using a device to protect them from the immune system. Vertex thinks these technologies are the breakthroughs the field needs to industrialize the concept.

Leiden said, We were watching companies who are addressing those two problems for the last two, three years. And over the last six to eight months, we were convinced that Semma has actually solved both of those problems.

Vertex reached that conclusion on the strength of preclinical data. Now, Vertex is set to invest to find out whether the idea works in the clinic.

Original post:

Vertex invests in gene therapy manufacturing - BioPharma-Reporter.com

Scientists are working to eliminate a type of heart disease in dogs using gene therapy.

They're zoning in on a heart condition called mitral valve disease thats common in 6% of dogs.

Scientists are using Cavalier King Charles spaniels for the research.

They tend to develop it at a younger age.

Scientists at Tufts University have already tested gene therapy in mice.

A virus is injected into them to deliver DNA to cells which causes them to create a protein.

What it essentially does is stops the heart valve from getting thicker, stopping the valve from leaking.

Researchers are now moving on to testing this in dogs.

But they think the treatment could go beyond just canines.

Many of the dog diseases are naturally occurring and really great models for human disease, says Dr. Vicky Yang, a veterinary cardiologist and research assistant professor at Cummings School of Veterinary Medicine at Tufts University. And I can see this, if it becomes successful in dogs, potentially going into thinking about treatment for humans for mitral valve disease.

The biotech company behind the treatment agrees. It says it could also expand beyond heart problems.

I think a larger question, though, is if we are able to prove this thesis of treating aging, making the animal generally healthier, could also treat heart failure, what other diseases could we treat in dogs? says Daniel Oliver, the CEO of Rejuvenate Bio. And could we progress this treatment onto past dogs and other animals and possibly humans?

The gene therapy would only be used for dogs just starting to experience heart problems.

Researchers still need to make sure the gene therapy is safe for all breeds before they make it available to the public.

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Scientists are using gene therapy to treat a heart disease in dogs. Could humans be next? - 10News

Updated results from the Alta trial show that a single infusion with the highest dose of SB-525, an investigational gene therapy, yields dose-dependent and durable increases in clotting factor VIII (FVIII). The trial, in adults with severe hemophilia A , found no bleeding episodes up to 24 weeks following the infusion.

That highest dose of SB-525 31013 vector genomes, vg/kilogram, kg led patients to reach normal FVIII activity. Participants no longer needed replacement therapy following a short preventive course post-SB-525-administration.

With these promising results, Pfizer has initiated a lead-in study (NCT03587116) to support SB-525 advancement to a Phase 3 registrational clinical trial. The six-month study will evaluate the current efficacy and safety of preventive replacement therapy in the usual care setting. It is currently recruiting participants worldwide.

The Alta trials most recent findings will be shared at the upcoming 61st Annual Meeting of the American Society of Hematology (ASH), to be held Dec. 7-10 in Orlando, Fla.

Data will be featured in a poster titled Updated Follow-up of the Alta Study, a Phase 1/2, Open Label, Adaptive, Dose-Ranging Study to Assess the Safety and Tolerability of SB-525 Gene Therapy in Adult Patients with Severe Hemophilia A.

SB-525 is a gene therapy candidate to treat hemophilia A thats being developed by Sangamo Therapeutics in collaboration with Pfizer. It consists of a DNA sequence coding for the production of a working FVIII the clotting factor missing in hemophilia A. That FVIII is carried and delivered to liver cells, where clotting factors are produced, using a harmless adeno-associated viral (AAV) vector.

The goal of the therapy is for patients to regain the ability to continuously produce the coagulation factor, and reduce or eliminate the need for FVIII replacement therapy.

The therapys safety and effectiveness for the treatment of adults with severe hemophilia A are currently being evaluated in the open-label Phase 1/2 Alta trial (NCT03061201).

The study is testing a single infusion into the vein (intravenous) of one of four ascending doses of SB-525: 91011 vg/kg; 21012 vg/kg; 11013 vg/kg; and 31013 vg/kg. Two people have been dosed per group, except for the highest dose group, which was expanded to five patients.

Updated trial data now released show the results for the two patients dosed in the third group those given 11013 vg/kg and the five individuals receiving the highest dose of 31013 vg/kg.

In the third group, a single infusion of SB-525 resulted in stable and clinically relevant increases in FVIII activity.

Stronger results were seen with SB-525s highest dose. Of the five patients treated, data were available for four. For these participants, a single infusion with the highest dose of SB-525 led to normal FVIII levels with no bleeding events reported up to 24 weeks post-administration. These individuals no longer needed replacement therapy after the initial prophylactic period of up to about three weeks after SB-525 dosing.

In addition, preliminary tests from the high-dose group indicate similar activity of SB-525-derived FVIII and the clotting factor provided by Xyntha, Pfizers recombinant therapy for hemophilia A.

As to safety, one patient had treatment-related serious adverse events, namely low blood pressure and fever, occurring about six hours after infusion. These effects resolved with treatment within 24 hours, with no loss of FVIII expression.

Some patients also showed elevated blood levels of liver enzymes(ALT, alanine aminotransferase). However, these were reported to be mild and temporary increases, which were treated in a timely manner with corticosteroids.

Dosing in the fourth group is ongoing. At the upcoming meeting, Sangamo will disclose additional analyses of the trial data, including a follow-up of approximately 4 to 11 months after treatment.

The rapid kinetics of Factor VIII expression, durability of response, and the relatively low intra-cohort variability in the context of a complete cessation of bleeding events and elimination of exogenous Factor VIII usage continues to suggest SB-525 is a differentiated hemophilia A gene therapy, Bettina Cockroft, MD, MBA, chief medical officer of Sangamo said in a press release.

We are pleased with the progress of the program toward a registrational Phase 3 study led by Pfizer, who announced it has enrolled its first patient in the 6-month Phase 3 lead-in study. We have recently completed the manufacturing technology transfer to Pfizer and initiated the transfer of the IND [investigational new drug].

Ana is a molecular biologist enthusiastic about innovation and communication. In her role as a science writer she wishes to bring the advances in medical science and technology closer to the public, particularly to those most in need of them. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she focused her research on molecular biology, epigenetics and infectious diseases.

Total Posts: 121

Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Tcnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.

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Updated Alta Trial Results Support SB-525 Gene Therapy for Hemophilia A - Hemophilia News Today

BRISBANE, Calif.--(BUSINESS WIRE)--Sangamo Therapeutics, Inc. (NASDAQ: SGMO), a genomic medicine company, today announced that hemophilia A gene therapy clinical data and hemoglobinopathies ex vivo gene-edited cell therapy data will be featured in poster presentations at the 61st Annual Meeting of the American Society of Hematology (ASH). The ASH abstracts, which were submitted on August 3, 2019, were released online this morning. The conference will take place in Orlando, FL, from December 7-10, 2019.

Gene Therapy

The SB-525 poster will show updated Alta study data including durability of Factor VIII (FVIII) levels, bleeding rate, factor usage, and safety, for all five patients in the high dose cohort of 3e13 vg/kg, with approximately 4 months to 11 months of follow-up after treatment with SB-525.

As of the abstract submission date, four patients in the 3e13 vg/kg cohort achieved FVIII levels within the normal range with no bleeding events reported up to 24 weeks post-administration. These patients did not require FVIII replacement therapy following the initial prophylactic period of up to approximately 3 weeks post-SB-525 administration. The fifth patient in the 3e13 vg/kg cohort had only recently undergone treatment with SB-525 at the time of the abstract submission. As previously reported, one patient had treatment-related serious adverse events (SAEs) of hypotension and fever, which occurred approximately 6 hours after completion of the vector infusion and resolved with treatment within 24 hours, with no loss of FVIII expression. SB-525 is being developed as part of a global collaboration between Sangamo and Pfizer.

The rapid kinetics of Factor VIII expression, durability of response, and the relatively low intra-cohort variability in the context of a complete cessation of bleeding events and elimination of exogenous Factor VIII usage continues to suggest SB-525 is a differentiated hemophilia A gene therapy, said Bettina Cockroft, M.D., M.B.A., Chief Medical Officer of Sangamo, commenting on the published abstract. We are pleased with the progress of the program toward a registrational Phase 3 study led by Pfizer, who announced it has enrolled its first patient in the 6-month Phase 3 lead-in study. We have recently completed the manufacturing technology transfer to Pfizer and initiated the transfer of the IND.

Ex Vivo Gene-Edited Cell Therapy

The ST-400 beta thalassemia poster will show preliminary results from the first three patients enrolled in the Phase 1/2 THALES study. In this study, hematopoietic stem progenitor cells (HSPCs) are apheresed from the patient, edited to knock out the erythroid specific enhancer of the BCL11A gene, and cryopreserved prior to infusion back into the patient following myeloablative conditioning with busulfan. The first three patients all have severe beta thalassemia genotypes: 0/0, homozygous for the severe + IVS-I-5 (G>C) mutation, and 0/+ genotype including the severe IVS-II-654 (C>T) mutation, respectively.

As of the abstract submission date, Patient 1 and Patient 2 had experienced prompt hematopoietic reconstitution. Patient 1 had increasing fetal hemoglobin (HbF) fraction that contributed to a stable total hemoglobin. After being free from packed red blood cell (PRBC) transfusions for 6 weeks, the patient subsequently required intermittent transfusions. Patient 2 had rising HbF levels observed through 90 days post-infusion. For both patients, as of the most recent follow-up reported in the abstract, on-target insertions and deletions (indels) were present in circulating white blood cells. Patient 3 had just completed ST-400 manufacturing at the time of abstract submission. As previously disclosed, Patient 1 experienced an SAE of hypersensitivity during ST-400 infusion considered by the investigator to be related to the product cryoprotectant, DSMO, and which resolved by the end of the infusion. No other SAEs related to ST-400 have been reported and all other AEs have been consistent with myeloablation. No clonal hematopoiesis has been observed. Longer follow-up will be required to assess the clinical significance of these early results. ST-400 is being developed as part of a global collaboration between Sangamo and Sanofi, along with support through a grant from the California Institute for Regenerative Medicine (CIRM).

The first three patients enrolled in the THALES study all have severe beta thalassemia genotypes that result in almost no endogenous beta globin production. The increases in fetal hemoglobin and presence of on-target indels in circulating blood cells suggests successful editing using zinc finger nucleases. The results are preliminary and will require additional patients and longer-term follow-up to assess their clinical significance, said Adrian Woolfson, BM., B.Ch., Ph.D., Head of Research and Development. It is important to note that myeloablative hematopoietic stem cell transplantation reboots the hematopoietic system, and that sufficient time is required for the stem cells to fully repopulate the marrow and for new blood cells to form. In other myeloablative conditioning studies in a similar patient population, full manifestation of the effects of gene modification in the red blood cell compartment has taken as long as 12 months or more to become evident.

Sanofis in vitro sickle cell disease poster details a similar approach to ST-400, using mobilized HSPCs from normal donors and SCD patients and utilizing the same zinc finger nuclease for gene editing, delivered as transient non-viral RNA, and designed to disrupt the erythroid specific enhancer of the BCL11A gene, which represses the expression of the gamma globin genes, thereby switching off HbF synthesis. Results from ex vivo studies demonstrated enriched biallelic editing, increased HbF, and reduced sickling in erythroid cells derived from non-treated sickle cell disease patients. Sanofi has initiated a Phase 1/2 trial evaluating BIVV003, an ex vivo gene-edited cell therapy using ZFN gene editing technology to modify autologous hematopoietic stem cells using fetal hemoglobin to produce functional red blood cells with higher BhF content that are resistant to sickling in patients with severe sickle cell disease. Recruitment is ongoing.

About the Alta study

The Phase 1/2 Alta study is an open-label, dose-ranging clinical trial designed to assess the safety and tolerability of SB-525 gene therapy in patients with severe hemophilia A. SB-525 was administered to 11 patients in 4 cohorts of 2 patients each across 4 ascending doses (9e11 vg/kg, 2e12 vg/kg, 1e13vg/kg and 3e13vg/kg) with expansion of the highest dose cohort by 3 additional patients. The U.S. Food and Drug Administration (FDA) has granted Orphan Drug, Fast Track, and regenerative medicine advanced therapy (RMAT) designations to SB-525, which also received Orphan Medicinal Product designation from the European Medicines Agency.

About the THALES study

The Phase 1/2 THALES study is a single-arm, multi-site study to assess the safety, tolerability, and efficacy of ST-400 autologous hematopoietic stem cell transplant in 6 patients with transfusion-dependent beta thalassemia (TDT). ST-400 is manufactured by ex vivo gene editing of a patient's own (autologous) hematopoietic stem cells using non-viral delivery of zinc finger nuclease technology. The THALES study inclusion criteria include all patients with TDT (0/0 or non- 0/0) who have received at least 8 packed red blood cell transfusions per year for the two years before enrollment in the study. The FDA has granted Orphan Drug status to ST-400.

About Sangamo Therapeutics

Sangamo Therapeutics, Inc. is focused on translating ground-breaking science into genomic medicines with the potential to transform patients' lives using gene therapy, ex vivo gene-edited cell therapy, in vivo genome editing, and gene regulation. For more information about Sangamo, visit http://www.sangamo.com.

Forward-Looking Statements

This press release contains forward-looking statements regarding Sangamo's current expectations. These forward-looking statements include, without limitation, statements regarding the Company's ability to develop and commercialize product candidates to address genetic diseases with the Company's proprietary technologies, as well as the timing of commencement of clinical programs and the anticipated benefits therefrom. These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, the outcomes of clinical trials, the uncertain regulatory approval process, uncertainties related to the execution of clinical trials, Sangamo's reliance on partners and other third-parties to meet their clinical and manufacturing obligations, and the ability to maintain strategic partnerships. Further, there can be no assurance that the necessary regulatory approvals will be obtained or that Sangamo and its partners will be able to develop commercially viable product candidates. Actual results may differ from those projected in forward-looking statements due to risks and uncertainties that exist in Sangamo's operations and business environments. These risks and uncertainties are described more fully in Sangamo's Annual Report on Form 10-K for the year ended December 31, 2018 as filed with the Securities and Exchange Commission and Sangamo's most recent Quarterly Report on Form 10-Q. Forward-looking statements contained in this announcement are made as of this date, and Sangamo undertakes no duty to update such information except as required under applicable law.

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Sangamo Announces Gene Therapy and Ex Vivo Gene-Edited Cell Therapy Data Presentations at the American Society of Hematology Annual Meeting - Business...

A new protein that can enhance the accuracy of CRISPR gene therapy was recently developed by researchers from City University of Hong Kong (CityU) and Karolinska Institutet. This work, published in the Proceedings of the National Academy of Sciences, could potentially have a strong impact on how gene therapies are administered in the future.

CRISPR-Cas9, often referred to as just CRISPR, is a powerful gene-editing technology that has the potential to treat a myriad of genetic diseases such as beta-thalassemia and sickle cell anemia. As opposed to traditional gene therapies, which involve the introduction of healthy copies of a gene to a patient, CRISPR repairs the genetic mutation underlying a disease to restore function.

CRISPR-Cas9 was discovered in the bacterial immune system, where it is used to defend against and deactivate invading viral DNA. Cas9 is an endonuclease, or an enzyme that can selectively cut DNA. The Cas9 enzyme is complexed with a guide RNA molecule to form what is known as CRISPR-Cas9. Cas9 is often referred to as the molecular scissors, being that they cut and remove defective portions of DNA. Being that it is not perfectly precise, the enzyme will sometimes make unintended cuts in the DNA that can cause serious consequences. For this reason, enhancing the precision of the CRISPR-Cas9 system is of paramount importance.

Two versions of Cas9 are currently being used in CRISPR therapies: SpCas9 (derived from the bacteriaStreptococcus pyogenes) and SaCas9 (derived fromStaphylococcus aureus). Researchers have engineered variants of the SpCas9 enzyme to improve its precision, but these variants are too large to fit into the adeno-associated viral (AAV) vector that is often used to administer CRISPR to living organisms. SaCas9, however, is a much smaller protein that can easily fit into AAV vectors to deliver gene therapy in vivo. Being that no SaCas9 variants with enhanced precision are currently available, these CityU researchers aimed to identify a viable variant.

This recent research led to the successful engineering of SaCas9-HF, a Cas9 variant with high accuracy in genome-wide targeting in human cells and preserved efficiency. This work was led by Dr. Zheng Zongli, Assistant Professor of Department of Biomedical Sciences at CityU and the Ming Wai Lau Centre for Reparative Medicine of Karolinska Institutet in Hong Kong, and Dr. Shi Jiahai, Assistant Professor of Department of Biomedical Sciences at CityU.

Their work was based on a rigorous evaluation of 24 targeted human genetic locations which compared the wild-type SaCas9 to the SaCas9-HF. The new Cas9 variant was found to reduce the off-target activity by about 90% for targets with very similar sequences that are prone to errors by the wild-type enzyme. For targets that pose less of a challenge to the wild-type enzyme, SaCas9-HF made almost no detectable errors.

Our development of this new SaCas9 provides an alternative to the wild-type Cas9 toolbox, where highly precise genome editing is needed, explained Zheng. It will be particularly useful for future gene therapy using AAV vectors to deliver genome editing drug in vivo and would be compatible with the latest prime editing CRISPR platform, which can search-and-replace the targeted genes.

Dr. Shi and Dr. Zheng are the corresponding authors of this publication. The first authors are PhD student Tan Yuanyan from CityUs Department of Biomedical Sciences and Senior Research Assistant Dr. Athena H. Y. Chu from Ming Wai Lau Centre for Reparative Medicine (MWLC) at Karolinska Institutet in Hong Kong. Other members of the research team were CityUs Dr. Xiong Wenjun, Assistant Professor of Department of Biomedical Sciences, research assistant Bao Siyu (now at MWLC), PhD students Hoang Anh Duc and Firaol Tamiru Kebede, and Professor Ji Mingfang from the Zhongshan Peoples Hospital.

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Modified Protein Enhances the Accuracy of CRISPR Gene Therapy - DocWire News

"We are excited to have reached this important milestone in the clinical evaluation of INXN-4001 for treatment of end-stage heart failure," stated Amit Patel, MD, MS, Co-Founder and Medical Director of TripleGene. "Heart failure rarely results from a single genetic defect, and while single gene therapy approaches have been studied, these treatments may not fully address the causes of the disease. Our unique multigenic approach is designed to stimulate biological activity targeting multiple points in the disease progression pathway."

Triple-Gene's investigational therapy uses non-viral delivery of a constitutively expressed multigenic plasmid designed to express human S100A1, SDF-1, and VEGF165 gene products, which affect progenitor cell recruitment, angiogenesis, and calcium handling, respectively, and target the underlying molecular mechanisms of pathological myocardial remodeling. The plasmid therapy is delivered via RCSI which allows for cardiac-specific delivery to the ventricle.

"Heart failure is the leading cause of death worldwide and represents a significant and growing global health problem. Aside from heart transplant and LVAD, current treatment options for those patients with end-stage disease are limited," commented Timothy Henry, MD, FACC, MSCAI, Medical Director of the Carl and Edyth Lindner Center for Research and Education at The Christ Hospital and a member of the Triple-Gene Medical Advisory Board. "The INXN4001 investigational therapy represents a biologically-based method focused on repairing the multiple malfunctions of cardiomyocytes, and I look forward to seeing the results of this initial safety study and further exploring the promise of this innovative treatment approach."

Triple-Gene will present preliminary data from the Phase 1 study at theAmerican Heart Association Scientific Sessionsat the Pennsylvania Convention Center in Philadelphia. A poster titled "Safety of First in Human Triple-Gene Therapy Candidate for Heart Failure Patients" will be presented on Sunday, November 17thfrom 3:00 pm - 3:30 pm ETin Zone 4 of the Science and Technology Hall.

About the Phase 1 Trial of INXN-4001INXN-4001 is being evaluated in a Phase I open label study in adult patients with implanted Left Ventricular Assist Device (LVAD). The study is designed to investigate the safety and feasibility of supplemental cardiac expression of S100A1, SDF-1 and VEGF-165 from a single, multigenic plasmid delivered via Retrograde Coronary Sinus Infusion (RCSI) in stable patients implanted with a LVAD for mechanical support of end-stage heart failure. Twelve stable patients with an implanted LVAD were allocated into 2 cohorts (6 subjects each) to evaluate the safety and feasibility of infusing 80mg of INXN4001 in either a 40mL (Cohort 1) or 80mL (Cohort 2) volume. The primary endpoint of safety and feasibility is assessed at the 6-month endpoint. Daily activity data are also collected throughout the study using a wearable biosensor. Dosing on both Cohorts 1 and 2 has been completed, and patients continue follow-up per protocol.

About Triple-GeneTriple-Gene LLC is a clinical stage gene therapy company focused on advancing targeted, controllable, and multigenic gene therapies for the treatment of complex cardiovascular diseases. The Company's lead product is a non-viral investigational gene therapy candidate that drives expression of three candidate effector genes involved in heart failure. Triple-Gene is a majority owned subsidiary ofIntrexon Corporation(NASDAQ: XON) co-founded by Amit Patel, MD, MS, and Thomas D. Reed, PhD, Founder and Chief Science Officer of Intrexon. Learn more about Triple-Gene atwww.3GTx.com.

About Intrexon CorporationIntrexon Corporation (NASDAQ: XON) is Powering the Bioindustrial Revolution with Better DNAto create biologically-based products that improve the quality of life and the health of the planet through two operating units Intrexon Health and Intrexon Bioengineering. Intrexon Health is focused on addressing unmet medical needs through a diverse spectrum of therapeutic modalities, including gene and cell therapies, microbial bioproduction, and regenerative medicine. Intrexon Bioengineering seeks to address global challenges across food, agriculture, environmental, energy, and industrial fields by advancing biologically engineered solutions to improve sustainability and efficiency. Our integrated technology suite provides industrial-scale design and development of complex biological systems delivering unprecedented control, quality, function, and performance of living cells. We call our synthetic biology approach Better DNA, and we invite you to discover more atwww.dna.comor follow us on Twitter at@Intrexon, onFacebook, andLinkedIn.

TrademarksIntrexon, Powering the Bioindustrial Revolution with Better DNA,and Better DNA are trademarks of Intrexon and/or its affiliates. Other names may be trademarks of their respective owners.

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Triple-Gene Announces Completion of Enrollment and Dosing in Phase 1 Trial of INXN4001, First Multigenic Investigational Therapeutic Candidate for...

GENES are the building blocks of life but like all things, they can sometimes go wrong, resulting in a range of conditions and diseases.

Repairing or replacing these genes with good ones, however, could solve or at the very least treat the problem, and this is what the emerging science of gene therapy is all about.

It was first suggested in the early-1970s that using good DNA (genes are short sections of DNA) to replace defective DNA could treat inherited diseases, and since then scientists have been trying to work out how to do it, both for inherited conditions and many others.

The British Society for Gene and Cell Therapy (bsgct.org) says the first approved human gene therapy took place in 1990, on four-year-old Ashanti DeSilva who had ADA-SCID an inherited disease that prevents normal development of the immune system. The therapy made a huge difference, meaning the little girl no longer needed to be kept in isolation and could go to school.

When the human genome was mapped nearly 20 years ago, the notion that it could potentially unlock therapies capable of fixing genes responsible for some of the worlds most devastating diseases was an idea of the future, says gene therapy expert Professor Bobby Gaspar, speaking on behalf of Jeans for Genes Day, the annual campaign for Genetic Disorders UK (geneticdisordersuk.org).

We are at the forefront of a new era of treatment for genetic diseases using gene and cell therapies. Some of these are one-time, potentially curative investigational therapies that could provide life-changing benefits to patients and their families.

Gaspar says there are currently more than 10 cell and gene therapy products approved in the European Union, ranging from products that treat cancer to rare immune deficiencies. A number of these are approved in the UK and available on its National Health Service in specialised centres.

And with nearly 3,000 clinical gene therapy trials underway worldwide, the number of available treatments is expected to grow significantly over the next few years.

Here, Gaspar a professor of paediatrics and immunology at the UCL Great Ormond Street Institute of Child Health and chief scientific officer at Orchard Therapeutics, a gene therapy company that seeks to permanently correct rare, often-fatal diseases outlines five of the ways gene therapy can cure, stop, or slow a disease...

A variety of efforts are underway to use gene therapy to treat cancer. Some types of gene therapy aim to boost the bodys immune cells to attack cancer cells, while others are designed to attack the cancer cells directly.

One way the body protects itself from cancer is through T-cells, a main component of the immune system. But some cancers are good at avoiding these protection mechanisms, says Gaspar.

Chimeric antigen receptor, or CAR T-cell therapy, is a new form of immunotherapy that uses specially altered T-cells to more specifically target cancer cells.

Some of the patients T-cells are collected from their blood, then genetically modified to produce special CAR proteins on the surface.

When these CAR T-cells are reinfused into the patient, the new receptors help the T-cells identify and attack cancer cells specifically and kill them.

There are more than 250 genetic mutations that can lead to a type of blindness called inherited retinal diseases, or IRD. People with a defect in the RPE65 gene start losing their vision in childhood.

As the disease progresses, patients experience gradual loss of peripheral and central vision, which can eventually lead to blindness.

Gene therapy for some IRD patients became available in 2017, delivering a normal copy of the RPE65 gene directly to the retinal cells at the back of the eye using a naturally-occurring virus as a delivery vehicle.

For children with the genetic disorder spinal muscular atrophy, or SMA, a rare muscular dystrophy, motor nerve cells in the spinal cord are damaged, causing patients to lose muscle strength and the ability to walk, eat or even breathe, says Gaspar.

SMA is caused by a mutation in a gene called SMN which is critical to the function of the nerves that control muscle movement. Without this gene, those nerve cells cant properly function and eventually die, leading to debilitating and often fatal muscle weakness.

Researchers recently developed the first US-approved gene therapy to treat children less than two years of age with SMA.

The therapy is designed to target the cause of SMA by replacing the missing or nonworking gene with a new, working copy of a human SMN gene, helping motor neuron cells work properly.

Researchers believe targeted gene therapy and gene editing may have widespread application for a range of infectious diseases that arent amenable to standard clinical management, including HIV.

Although HIV isnt a hereditary disease, the virus does live and replicate in DNA, Gaspar explains.

Another early but encouraging approach uses a gene editing technology combined with a new long-acting, antiretroviral treatment to suppress HIV replication and eliminate HIV from cells and organs of infected animals.

Gene editing is an approach that precisely and efficiently modifies the DNA within a cell. In this approach, gene editing can knock out a receptor called CCR5 on immune cells used by HIV to enter and invade cells. Without CCR5, HIV may no longer invade and cause disease.

One approach being investigated for a number of rare, often-fatal diseases uses gene-modified blood stem cells with a goal of permanently correcting the underlying cause of disease.

Blood stem cells are taken from the patient, and corrected outside the body by introducing a working copy of the gene into the cells. The gene-corrected cells are then put back into the patient to potentially cure the disease.

Gene-modified blood stem cells have the capacity to self-renew and, once taken up in the bone marrow, can potentially provide a lifelong supply of corrected cells. Because of their ability to become many different types of cells in the body, this approach has the potential to provide a lasting treatment for many different severe and often life-limiting inherited disorders, many of which have no approved treatment options available, says Gaspar.

For instance, ADA-SCID, sometimes referred to as bubble baby syndrome, is a disease where babies lack almost all immune protection, leading to frequent and devastating infections. Left untreated, babies rarely live past two years of age. Standard treatment options are not always effective or can carry significant risks. In 2016, the European Medicines Agency approved Strimvelis, a blood stem cell gene therapy for the treatment of ADA-SCID. Strimvelis was the first approved ex vivo gene therapy product in Europe.

Jeans for Genes Day helped fund some of the earliest work using this type of gene therapy at Great Ormond Street Hospital in 2002, when Rhys Evans, a little boy with SCID, became one of the first children worldwide to be treated by gene therapy.

Jeans for Genes Day aims to raise money for children with life-altering genetic disorders by asking people to donate money for wearing jeans to work, school or wherever they like, on any day between September 16-20. Visit jeansforgenesday.org.

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Five benefits of gene therapies - Echo Live

How will Cell and Gene Therapy Usher in a New Industrial Revolution?

Cell and gene therapy companies are on the verge of transforming how we treat unmet medical needs such as cancer, rare diseases, genetic disorders and diabetes, to name only a few. By using a patients own cells and genes to fight disease, cell and gene therapy treatments deliver highly-targeted therapies and cures for unserved and underserved patients in need of solutions to a wide variety of intractable diseases.

What was once relegated to science fictionlike the miniaturized heroes sent into a human body in the Fantastic Voyage sci-fi movie of 1966has, to a large degree, become reality with modified cells being put into patients to act as virtual bots capable of clearing diseaseseven cancersfrom the body. New technologies are empowering science to do what would never have been thought possible years ago.

Understanding the complexities of how these novel personalized medicines actually work can be daunting and confusing for many people, especially for the patients who are in need of these new medicines and those who are non-scientific minded.

Jeff Galvin, CEO of American Gene Technologies (AGT), has helped a wide variety of audiences understand this new technology by explaining the similarities between the human cell and an organic computer. He explains that DNA is the operating system of the human cell. It contains commands for the cellular machinery called genes, which are coded in four symbols: A, G, T, and C (for the nucleotides adenine, guanine, thymine, and cytosine). The order of these nucleotides determines the instruction that a gene provides to the machine just like the order of 1s and 0s in your personal computer or cell phone determine the commands to be executed by the device. Galvin coined this human computer analogy to describe the work that his company is doing and what is actually taking place with cell and gene therapies to make new solutions for formerly unaddressable human diseases.

Galvin describes gene and cell therapy as the software revolution for the next 100 years: reprogramming DNA in cells to improve health. Scientists have long understood that viruses infect cells and hijack them with new instructions (viral DNA) to cause disease. Over the last few decades, methods have been developed to crack open viruses, scoop out their bad instructions that make cells sick, and replace them with new good instructions that improve the operation of the cell. In a way, the gene and cell therapy industry is hijacking the hijacker, says Galvin. We are taking viruses and converting them to updates to fix bugs or improve the operating system (DNA) of human cells. Just like viruses and updates on your computer work. The possibilities are endless. We can use these updates to repair a broken gene that is the root cause of a disease, insert new instructions into cells to improve their operation allowing them to do their jobs better, clear or protect the body from disease, or even change the operation of cells to make them little bots that can carry out functions that they would not normally do in your body, like clearing cancer. All of these things are within the scope of reprogramming the human computer.

American Gene Technologies (AGT), a biotech company located in Rockville, Maryland, is a company where Silicon Valley tech innovation and the human computer mindset is converging to rethink the approach to developing medicine.

AGTs CEO Jeff Galvin has shared that he and other cell and gene therapy leaders are on a mission to reprogram the human computer to save lives and improve outcomes for patients fighting infectious diseases, monogenic disorders, cancer and other devastating illnesses.

A serial tech innovator, Galvin made his mark as a Silicon Valley entrepreneur. He retired in his early 40s in 2002. His retirement was short-lived. When Galvin discovered the groundbreaking viral vector work of the National Institute of Healths (NIH) Dr. Roscoe Brady, he exited retirement to do what he always does: Vigorously pursue what he loves.

Galvin leapt out of retirementin 2007 to start AGT, and to continue developing Bradys technology.

I was very lucky to meet Roscoe Brady. When he showed me viral vectors and I realized we now had the ability to modify DNA with viruses, I immediately felt that this is the future of pharmaceuticals, stated Galvin. I could see the inherent power in this approach and how viral vectors could bring opportunities to new biotech companies to cure diseases that were formerly untreatable or incurable.

Bradys commitment to solving diseases and improving lives was also infectious. Dr. Brady was retiring, and it looked like this brilliant work was going to be shelved. explains Galvin. I saw it as too valuable and potentially world-changing to ignore. Dr. Brady agreed to stay on as a scientific advisor and I founded AGT with the mission to find the most efficient, effective, and fastest ways to bring this cutting edge technology to patients in need.

A lot of what I imagined as a computer programmer and software/IT specialist coming from the West Coast is actually coming true for this technology. This vision has fortunately attracted a lot of great scientists to our company and they are doing all of the rocket science. The concept is correct: We can use viral vectors to hijack the viruses that have been hijacking our cells for 1.5 billion years, using the inherent ability of viruses to infect cells and carry malevolent genetic code to deliver benevolent code instead,. Galvin stated.

What I am witnessing in our part of this industry is that high tech has come to drug development. The capabilities of everything we are doing is doubling every yearits like the computer revolution; every year youre getting more power while the price of the technology is going down, so youre getting exponential growth in power and value, Galvin commented.

Our approach is a major shift from old-style drug development, which relies on the random generation of thousands or tens of thousands of molecules. And then you try to screen them down via a cell model that gives you the effect youre looking for. And generally after two years and $10 million of investment, you have a few (drug programs) you can test in a mouse, and then one in 19 get into the clinic, stated Galvin.

What were doing at AGT and in the cell and gene therapy field is just different. Gene and cell therapy is about directed development. You can create highly targeted drugs that hit a specific cellular pathway and you can even narrow that down using specific promoters or chimeric envelopes so you can direct that drug to a certain cell type or even to a certain disease indicator, stated Galvin. By narrowing the drug to the particular tissue or particular disease indicator you are sparing all the healthy tissue, which is the main reason drugs drop out of clinical development, the side effects. Gene and cell therapy largely avoids this issue.

We can test some of these in cell models at the bench, then in animal models and be able to get to a go-no-go decision after $100K in investment. We might be able to characterize it so well at the bench that the clinical development becomes highly predictable. This turned out to be true with our HIV therapy, stated Galvin.

Galvin believes that AGTs cell and gene therapy platform will help contributeas part of a wider cell and gene therapy revolutionto the eradication of the $2 to $4 trillion in palliative care treatment costs replaced with one-and-done cures. Viral-vector based drug development platforms like the one AGT deploys will help find new gene and cell therapy treatments and cures for the approximately 7,000 rare diseases that impact approximately one in ten people across the globe.

The future of drug development, in my mind, is that the toolset will keep evolving like computers and software. Software developers used creativity to leverage a limited toolset to create value in the market. At AGT, were thinking about correcting DNA to improve human health and mitigate disease. Everything about technology is playing in our favor. If you were in computers a while ago and you saw mainframes turn into mini-computers and then micro computers you would have said, Eventually we will have these things in our pocket and you would have been right. The same is now true about drug development, stated Galvin, Nearly anything will be possible in the future as this technology continues to exponentially improve. In this high-tech revolution of gene and cell therapy, if you can dream it, you will eventually be able to do it!

AGT is part of an evolving, growing and groundbreaking cell and gene therapy cluster thriving in the BioHealth Capital Region.

Maryland is at the epicenter of the gene and cell therapy technological explosion Its all about the resources. They are starting to hit a critical mass here, added Galvin.

Steve has over 20 years experience in copywriting, developing brand messaging and creating marketing strategies across a wide range of industries, including the biopharmaceutical, senior living, commercial real estate, IT and renewable energy sectors, among others. He is currently the Principal/Owner of StoryCore, a Frederick, Maryland-based content creation and execution consultancy focused on telling the unique stories of Maryland organizations.

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Reprogramming the Human Computer: Silicon Valley Meets Cell and Gene Therapy - BioBuzz

DURHAM Precision BioSciences, a genome-editing company based in Durham, has received authorization from the U.S. Food and Drug Administrationto advance its second genome-edited cancer therapy to clinical trials.

The FDA has accepted Precisions Investigational New Drug application for PBCAR20A to treat non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CCL), and small lymphocytic lymphoma (SSL).

Precisions technology is part of a new approach to fighting cancer using T cells a type of immune system cell that recognizes invading germs or cancer cells. T cells are engineered to carry a cancer bullet called a tumor-targetingchimericantigenreceptor (CAR). These engineered cells have the potential to save the lives of many patients unresponsive to traditional chemotherapy and radiation regimens.

Precision Biosciences

Autologous CAR T therapies currently on the market rely on patient-derived T cells, which are extracted and individually manufactured for each patient using that patients own cells. They require a complex and lengthy process.

Precisions allogeneic CAR T product candidates use T cells derived from qualified donors. The T cells are manufactured in large batches and are cryopreserved (safely preserved, intact, at extremely low temperatures) for shipment, storage and off-the-shelf use.

These allogeneic CAR T product candidates rely on Precisions ARCUS genome-editing platform to remove the T cell receptor to prevent graft versus host disease without the need for donor-patient matching. ARCUS editing also enables targeted insertion of the CAR gene into a single, specific location in the T cell genome for more controlled, consistent expression.

Pfizers 300 new jobs, $500M investment symbolize Triangles growth as gene therapy hub

The company said it will begin a Phase1/2a clinical trial later this year in non-Hodgkin lymphoma patients, including a subset of patients with a cancer called mantle cell lymphoma, for which Precision has received the FDAs Orphan Drug designation.

PBCAR20A is Precisions second off-the-shelf cell therapy. The company is also studying the precursor to PBCAR20A PBCAR0191 in adult patients who are not responding to other therapies. Technically, these are designated as patients with relapsed or refractory (R/R) NHL or R/R B-cell precursor acute lymphoblastic leukemia (B-ALL).

Both of Precisions treatments use the companys ARCUS genome editing technology to produce CAR T cells derived from healthy donors, rather than relying on cancer patients own blood. The development of these allogeneic CAR Ts is designed to overcome the manufacturing limitations of traditional autologous CAR T therapies, to target a broader range of malignancies, and to increase the number of patients who can potentially benefit.

FDA clearance to begin clinical trials with our anti-CD20 off-the-shelf therapy candidate is a significant milestone for Precision, said Matt Kane, the companys CEO and co-founder. Todays announcement demonstrates our ability to advance multiple product candidates in parallel into the clinic, leveraging the unique capabilities of our ARCUS genome editing platform, CAR T development approach and highly differentiated manufacturing process developed in-house.

Precision uses ARCUS to remove T cell receptors to prevent graft versus host disease, thus avoiding the need for donor-patient matching that is required in traditional tissue donation procedures. And the ARCUS technology also provides for the targeted insertion of the CAR gene into a single, specific location in the T cell genome for controlled, consistent expression. Precisions product candidates can be made in advance, manufactured in large batches and then cryopreserved for shipment, storage and off-the-shelf use.

AskBio gets $235 million in gene therapy support

PBCAR20A, if approved, will fill an important gap in current cancer treatments. In the United States, B-cell malignancies account for 85 percent of all non-Hodgkin lymphoma. And CLL and SLL represent 25 to 30 percent of leukemia cases. Precision said that, while front-line treatments benefit more than half of newly diagnosed NHL patients, at least a third of those achieve only partial remission or relapse after remission.And patients with CLL have limited success with autologous CAR T therapies. An allogeneic CAR T like PBCAR20A may overcome treatment resistance and offer the possibility of combination treatments.

It is our hope that PBCAR20A will provide a new allogeneic CAR T therapy option with the benefits of reliable, off-the-shelf access and optimized cellular activity to patients living with NHL or CLL/SLL, where a significant need for new treatment options remains, said David Thomson, Precisions chief development officer.

Precision Biosciences is a 2006 Duke University spin-out dedicated to improving life by using its ARCUS gene editing technology to treat human diseases and create healthy and sustainable food and agriculture solutions.

In 2018 the company created a new name and brand identity for its food and agriculture business,Elo Life Systems. The business is using Precisions ARCUS platform and other new technologies for applications in crop improvement, animal genetics, industrial biotechnology and sustainable agriculture.

(C) N.C. Biotech Center

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FDA approves 2nd gene therapy cancer drug from Durham's Precision Bio for clinical trial - WRAL Tech Wire

Kari Branham, M.S., a genetic counselor at Kellogg, worked with Zions family to help them understand the genetic basis for Zions condition.

SEE ALSO: Retinitis Pigmentosa in Children: 5 Facts Families Should Know

We have seen such amazing progress with these conditions over the last 15-20 years,says Branham. We used to tell patients and their families that we would have to wait and see what happens, but now we can actually do something to help.

By going through the gene therapy process, Branham says the team is hopeful that this has changed Zions prognosis.

The treatment is designed to stop or slow the death of specialized cells in the retina, called photoreceptors, that send visual information to the brain.

Patients who have Leber congenital amaurosis have night blindness, says Besirli. One of the first treatment effects after receiving Luxturna is that (patients) are telling us that they function much better in dark.

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They can play outside much longer, they can navigate around the house and dont need nightlights anymore and can participate in indoor sports. Thats been a huge change in their lives.

Seven months after treatment, Zion, now age 7, and his family are back to their normal routine in Montrose, Mich., and monitor his progress during follow-up appointments at Kellogg.

Zion says hes looking forward to playing football and, with improved vision -- playing outside at night with his brothers.

We hope that with Zion we have changed the trajectory for him to the point that in his 20s he wont have significant vision loss we see with him now, says Branham.

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7-Year-Old Receives New FDA-Approved Retina Gene Therapy - University of Michigan Health System News

The first patient in a Phase 1/2 clinical trial of Fabry disease gene therapy candidate FLT190 has been dosed.

Enrollment is ongoing at the Royal Free Hospital, in London, U.K. More information and contacts are available here.

Fabry disease iscausedby a faulty GLAgene, which provides instructions to make an enzyme called alpha-galactosidase A (alpha-GAL A). When mutated, this gene leads to abnormal alpha-GAL A function, which results in the build-up of lipids (fatty molecules) known as globotriaosylceramide (Gb3) and globotriaosylsphingosine (LysoGb3) that can damage the heart, kidneys, or liver.

Freelines FLT190 is a gene therapy that uses an adeno-associated virus (AAV8) a harmless virus that does not cause disease or infection as a vehicle to deliver a healthy copy of the GLAgene in the hopes it will induce the production of normal alpha-GAL A. In contrast to the regular infusions of enzyme replacement therapy (ERT), this gene therapy is designed to be given in a single dose.

The international, multi-center MARVEL1 study (NCT04040049) will primarily study the safety of FLT190 in up to 12 adult male patients with classic (type 1) Fabry disease, as well as whether it results in continuous production of high levels of alpha-GAL A. Other goals include clearance of Gb3 and LysoGb3, alterations in kidney and skin biopsies, renal and cardiac function, assessing immune responses, and quality of life.

After taking FLT190 via slow intravenous infusion, participants will be monitored for nine months at outpatient visits, and then enter a long-term follow-up period. Both previously and untreated patients will be included, although in two separate parts dose escalation and dose expansion.

MARVEL1 is the first trial of an AAV-based gene therapy for Fabry disease, according to the company. The trial is estimated to end by March 2021.

The initiation of this clinical study is an important event for the patient community. I am hopeful that the promising preclinical data will translate into long term benefit for patients with Fabry [disease], Derralynn Hughes, MD, PhD, said in a press release. Hughes isa Fabry disease expert and senior lecturer at Royal Free Hospital.

Preclinical results in a mouse model of the disease revealed that a single injection of FLT190 into the blood led to a sustained increase of more than 1,000-fold in alpha-Gal A levels, compared to healthy mice. The levels of Gb3 were reduced markedly in the kidney, spleen and heart, as were those of LysoGb3, which have been suggested as anaccurate biomarker to diagnose and track Fabry disease. No adverse side effects were found.

Chris Hollowood, Freelines executive chairman, said that starting MARVEL1 and dosing the first patient is a significant milestone for the company.Continuous high expression of [alpha-GAL A] holds the potential for better treatment outcomes than is seen with ERT, the current standard of care. We believe we can access high expression at relatively low doses.

Besides Fabry disease, Freeline also is testing its AAV technology in hemophilia B, in which a Phase 2/3 trial (NCT03641703) is evaluating whether the potential gene therapy FLT180a is safe and provides long-term production of the clotting protein missing in these patients (factor IX).

These innovative gene therapies have the potential to change patients lives, Hollowood said.

Jos is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimers disease.

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First Patient Dosed in Trial of Fabry Gene Therapy Candidate FLT190 - Fabry Disease News

Last year, Bluebird Bio claimed anFDA breakthrough designation for its Lenti-D gene therapy for cerebral adrenoleukodystrophy (CALD) it has now revealed additional data to support a fast-track approval.

The updated results from the biotechs phase 2/3 Starbeam study were revealed at the European Paediatric Neurology Society (EPNS) congress in Athens, Greece.

CALD is caused by progressive destruction of the myelin sheath that surrounds nerves responsible for thinking and muscle control, resulting in a relentless deterioration that typically leads to a vegetative state or death within a few years of diagnosis. The condition mostly affects young males, with the majority of patients dying before the age of ten.

The only current treatment for the disease is stem cell transplant, but it carries a significant risk from the high-dose chemotherapy used to prepare patients for the procedure. Other potential complications include graft-versus-host (GvHD) disease, when the transplanted cells recognise the recipients cells as foreign and attack them.

Bluebird's treatment works by extracting patients' stem cells and modifying them with Lenti-D. They are then infused back into the patient, where they thenhave the potential to develop into multiple cell types that can produce a functional version of the ALD protein that is lacking in CALD.

Of the patient population involved in the study, as of 25 April 2019, 15 had completed the trial and are enrolled in a long-term follow-up study, 14 are currently still on-study, and three are no longer on-study.

The primary efficacy endpoint of the study is the number of patients who are alive and free of MFDs at month 24 MFDS are the six severe disabilities commonly attributed to CALD, which have the most severe effect on a patients ability to function independently.

The study demonstrated that of those patients who have or would reach 24 months of followup and complete the study, 88% continue to be MFD-free and alive. The 14 patients currently on study have less than 24 months of follow-up and have so far shown no evidence of MFDs.

Out of the 32 treated patients, three did not or will not meet the primary efficacy endpoint, two patients withdrew from the study and one experienced rapid disease progression early, which lead to MFDs and death.

The primary safety endpoint the number of patients experiencing GvHD by month 24 was also met. According to Bluebird, no events of acute or chronic GvHD were reported posttreatment and there were no reports of graft failure, cases of insertional oncogenesis or replication competent lentivirus. There were three adverse events potentially related to treatment of Lenti-D, but these resolved using standard measures.

Lenti-D is Bluebirds lead gene therapy programme,but the company has also made significant progress with its Celgene-partnered CAR-T cancer immunotherapy programme, reporting dramatic responses with its multiple myeloma candidatebb2121 last December.

It also received approval for its gene therapy Zynteglo earlier this year. The one-time gene therapy has been approved for patients 12 years and older with transfusion-dependent -thalassaemia (TDT), and has been shown in a series of small studies to free a majority of patients from the need to have regular blood transfusions.

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Bluebird bio reveals further encouraging data for CALD gene therapy - PMLiVE

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Newswise The Childrens Cancer Institute at the Joseph M. Sanzari Childrens Hospital at Hackensack Meridian Health Hackensack University Medical Center and the John Theurer Cancer Center have announced they are participating in a multicenter Phase I/II clinical trial of an investigational gene therapy from bluebird bio, Inc. This trial is specifically for adolescents and adults with severe sickle cell disease (SCD) who cannot be effectively treated using standard therapies such as antibiotics, vitamins, blood transfusions or any pain relieving medications. The study is evaluating the safety and effectiveness of LentiGlobin for sickle cell disease, a gene therapy produced using the patients own modified stem cells to treat their sickle cell disease.

By using the patients own cells to produce functional hemoglobin that can prevent sickling of their red blood cells, LentiGlobin for SCD offers patients the opportunity to treat their disease without the need to have a matched bone marrow donor. The John Theurer Cancer Center is one of a limited number of centers internationally, and the Joseph M. Sanzari Childrens Hospital is the only pediatric site in New Jersey, where the study, which is enrolling patients age 12-50, is taking place.

Sickle cell affects 100,000 Americans. It affects one in every 365 African American births and one in every 16,000 Hispanic American births, said Alfred P. Gillio, M.D., director, Childrens Cancer Institute and section chief, Pediatric Stem Cell Transplantation and Cellular Therapy Program, Joseph M. Sanzari Childrens Hospital at Hackensack University Medical Center. This trial is for patients who have severe sickle cell disease and seek advanced treatment options but do not have a well-matched stem cell donor. Only 15% of sickle cell patients have a matched sibling donor and only 25 percent of patients have a matched unrelated volunteer donor.

Sickle cell affects every organ in a patients body, said Stacey Rifkin-Zenenberg, D.O., FAAP, pediatric hematologist/oncologist, Childrens Cancer Institute, and section chief, Pain and Palliative Care, Joseph M. Sanzari Childrens Hospital at Hackensack University Medical Center. This disease really has a tremendous effect not only on the patient, but also the family.

Sickle cell disease is an inherited disease caused by a mutation in the beta-globin gene, resulting in abnormal hemoglobin and sickle-shaped red blood cells. Symptoms and complications of the disease include anemia, infections, stroke, poor quality of life and early death. To date, the only cure for sickle cell disease is receiving a stem cell transplant from a matched donor, but this is not a therapeutic option for many patients. Supportive care including hydroxyurea and blood transfusions can ameliorate symptoms of the disease. To date, without a marrow donor, there has been no alternate curative therapy. Life expectancy of a person with sickle cell disease is 20 to 40 years of age. In some cases, patients using disease modifying medications can live to 50 or 60.

This therapy may be a major advance for sickle cell patients and so far, the results look very promising, said Scott D. Rowley, M.D., FACP, hematologist, medical director, Stem Cell Transplantation and Cellular Therapy and medical director, BMT Cell Lab, John Theurer Cancer Center, Hackensack Meridian Health Hackensack University Medical Center, who is enrolling adult patients. This investigational treatment, which is a one-time therapy, may be an option for our patients who have no other treatment options.

The results from early clinical studies are encouraging, said Dr. Gillio. With this treatment, the patient is their own donor and we are modifying their own cells to add copies of a functional beta globin gene.

In the current study:

About Hackensack Meridian Health Hackensack University Medical Center

Hackensack Meridian Health Hackensack University Medical Center, a 781-bed nonprofit teaching and research hospital located in Bergen County, NJ, is the largest provider of inpatient and outpatient services in the state. Founded in 1888 as the countys first hospital, it is now part of the largest, most comprehensive and truly integrated health care network in New Jersey, offering a complete range of medical services, innovative research and life-enhancing care, which is comprised of 34,100 team members and more than 6,500 physicians. Hackensack University Medical Center is ranked #2 in New Jersey and #59 in the country in U.S. News & World Reports 2019-20 Best Hospital rankings and is ranked high-performing in the U.S. in colon cancer surgery,lung cancersurgery,COPD, heart failure, heart bypass surgery, aortic valve surgery,abdominal aortic aneurysm repair, knee replacement and hip replacement. Out of 4,500 hospitals evaluated, Hackensack is one of only 57 that received a top rating in all nine procedures and conditions. Hackensack University Medical Center is one of only five major academic medical centers in the nation to receive Healthgrades Americas 50 Best Hospitals Award for five or more years in a row. Beckers Hospital Review recognized Hackensack University Medical Center as one of the 100 Great Hospitals in America 2018. The medical center is one of the top 25 green hospitals in the country according to Practice Greenhealth, and received 26 Gold Seals of Approval by The Joint Commission more than any other hospital in the country. It was the first hospital in New Jersey and second in the nation to become a Magnet recognized hospital for nursing excellence; receiving its sixth consecutive designation in 2019. Hackensack University Medical Center has created an entire campus of award-winning care, including: John Theurer Cancer Center, a consortium member of the NCI-designated Georgetown Lombardi Comprehensive Cancer Center; the Heart & Vascular Hospital; and the Sarkis and Siran Gabrellian Womens and Childrens Pavilion, which houses the Joseph M. Sanzari Childrens Hospital and Donna A. Sanzari Womens Hospital, which was designed with The Deirdre Imus Environmental Health Center and listed on the Green Guides list of Top 10 Green Hospitals in the U.S. Hackensack University Medical Center is the Hometown Hospital of the New York Giants and the New York Red Bulls and is Official Medical Services Provider to THE NORTHERN TRUST PGA Golf Tournament. It remains committed to its community through fundraising and community events especially the Tackle Kids Cancer Campaign providing much needed research at the Childrens Cancer Institute housed at the Joseph M. Sanzari Childrens Hospital. To learn more, visit http://www.HackensackUMC.org.

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Joseph M. Sanzari Childrens Hospital and John Theurer Cancer Center Launch Clinical Trial Evaluating Gene Therapy for Severe Sickle Cell Disease in...

Tara Moore, a professor of personalised medicine at Ulster University, is working on a project that aims to develop a gene therapy treatment for corneal dystrophy.

The research, which Professor Moore discussed at a Four Liveries guest lecture for the Worshipful Company of Spectacle Makers at Painters Hall in London last week (12 September), is a collaboration between the Ulster University and Avellino Labs in the US.

Speaking to OT, Professor Moore explained: It is a new era of medicine where its much more personalised. Its not one-drug-fits-all or one therapy fits everyone. Its much more personalised to the person and to the exact reason that they have the disease they have.

The exact genetic mistake or mutation that causes [a persons] particular disease can be targeted now very specifically. We are now equipped with a way to target that DNA that we never thought would be possible, Professor Moore said.

Professor Moore and her team are applying CRISPR technologies to the eyes, specifically the front of the eye she explained. It is difficult to deliver to. But if we can overcome that battle, we can hopefully have a gene therapy that will be successful, she shared.

When discussing the future for the treatment, Professor Moore told OT: I would like to think we would end up at a stage in personalised medicine where everyone would be pre-screened for whatever mutations that they contain that predispose them to a particular disease and we could treat people.

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Personalised medicine: developing gene therapies - AOP

To a trained eye, the chromosome chart (karyotype) above has 4 irregularities, circled in red. Theyre chromosome pairs of uneven size.

The chromosomes represent genetic material missing or extra, but also a beautiful girl. Her father contacted me after he read my recent post about a friends child with a rare mutation in a single gene, a more typical driver of so-called diagnostic odysseys. Did I have any insight on treatments for his daughter? Hed send her lab reports.

The notations were in Hebrew, but the universal language of chromosome charts spoke clearly to me. The chromosome pairs are size-ordered, its members matching, but pairs 9, 14, 15, and 16 look like tall and short dance partners. This was something more profound than a single gene glitch, or even a missing or extra chromosome.

Shattered and Scattered

Aviya has an exceedingly rare condition called chromothripsis, which is Greek for shattered colored bodies. Breaks that sever both strands of the DNA double helix riddle one or more chromosomes. Lost pieces may have been ejected and glommed onto other chromosomes at or before fertilization, creating the karyotype that veers from the neat, normal, 23-pair organization.

Chromothripsis is best studied in cancer cells, where the genome is shot to smithereens, but only a few dozen people in the world are known to have it in all their cells. When the medical team at Schneider Childrens Medical Center in Israel discovered the childs condition, they told the parents that only 30 cases had been reported in the medical literature. Ever.

For some of the cases, researchers deduced how chromosomes broke long ago, in developing eggs. Since human eggs sit in an ovary for dozens of years before they mature at the moment of fertilization, enough time elapsed for natural DNA repair to fix some of the breaks and fill in small deletions.

In the few cases of fetuses surviving chromothripsis, enough of the genome must have been knit back together, even if in the wrong places, to sustain development and life. Sperm mature much too quickly, over a few months, to heal themselves in this way.

So a person with chromothripsis is about as rare as rare can be. Each case is unique, for the genomes of no two people that come apart in this highly unusual manner are stitched back together in exactly the same way.

The Diagnostic Odyssey

Aviya is now just past her second birthday and is beginning to walk, although she doesnt yet talk. Her symptoms unfolded early and rapidly, about 3 months after her birth in May 2017.

She started throwing up multiple times a day and regardless of how much or what she ate, breast milk or formula, she would not gain weight. She wasnt reaching developmental milestones. The physical therapist noted her hypotonia (low muscle tone, or floppiness), her dad recalled. Her weight steadily dropped, as the vomiting worsened.

Hospital stays followed. Tests and scans ruled out intestinal malrotation, while neurological tests and abdominal ultrasounds were normal too. Doctors inserted a nasogastric tube, for nutrition.

At 7 months old, Aviya started at the failure-to-thrive clinic at Schneiders, where she had tests and evaluations for physical therapy (PT) and occupational therapy (OT). She also met with an eating specialist.

Everyone poked and prodded and measured and checked. She had blood tests, gave stool samples, had CT scans, MRI images, and drank stuff for x-rays through the GI tract, Yosef said. The doctors initially suspected malrotation of the intestines behind the vomiting, but that didnt hold up. They didnt find any evidence or suspicion of anything amiss based on symptoms only, he added. Heart, brain, blood, all looked ok.

The next step: probing genetics. A chromosomal microarray test (CMA; for small deletions and insertions) and a karyotype revealed the four unusual chromosomes, deemed a complex chromosomal rearrangement. Tests for selected single-gene conditions, like Beckwith-Wiedemann syndrome, were negative.

Further analysis led to the chromothripsis explanation. Because the parents CMA tests and karyotypes were normal, their daughter hadnt inherited her unusual chromosomes they originated in her, likely an ultra rare event in a lone developing egg, followed by spectacular natural healing.

But deducing chromosomal origins and even contemplating whether a gene therapy might be possible for a situation so complex took a backseat to addressing Aviyas daily challenges. First, she had to be able to eat.

Focusing on Symptoms

Vomiting send Aviya to the hospital regularly. For 9 months she received supplemental feedings through a nasogastric tube, and the frequency of episodes slowed as she slowly gained weight. When the gaining once again slowed, and days-long bouts of vomiting led to more hospitalizations, doctors performed a procedure called PEG (for percutaneous endoscopic gastrostomy). A tube through the abdominal wall into her stomach now delivered nutrients. That was done on March 5th, 2019.

The vomiting finally ceased and Aviya has reached the 10th percentile in body weight, up from inexorably losing. Shes also catching up on gross motor skills and reaching developmental milestones. And shes intelligent. She understands basically everything you tell her, for the level of a 2-year-old, Yosef said. Thats pretty amazing considering the number of unusual chromosomes and how many genes affect brain function.

But boosting nutrition isnt the only intervention helping Aviya to overcome whatever limits her chromosomes have set. Yosef credits her overall improvement to the excellent care shes been receiving at a special education day care program near their home on the West Bank. Shes been attending since November, and she gets PT, OT, speech therapy, and does specialized exercises tailored to her abilities. Aviya also returns to the failure-to-thrive clinic every other month, down from once a week.

Instead of Fixing Genes, Address Symptoms

When parents become sucked down the rabbit hole of rare diseases, they quickly learn about biotech approaches: enzyme therapies, stem cells, antisense oligonucleotides, gene therapy, and even gene editing. Its overwhelming. Some of the parents DNA Science has featured rapidly became nearly as expert as some of the scientists developing new treatments (see Celebrating the Moms of Gene Therapy).

Would exome sequencing shed any more light on the situation, or it would just lead to more questions that no one has the answers to? Yosef asked me. Exome sequencing, which reveals the information in the part of the genome that encodes protein, might actually provide too much information, noting too many missing genes to consider treatments for all of them. But it might reveal which proteins Aviya cant make, and maybe that could lead to something.

The TMI issue also affects the utility of a gene therapy for chromothripsis: too many targets.

Specific mutations in single genes cause the conditions for which gene therapy has been FDA approved Luxturnato treat a form of inherited blindnessand Zolgensmato treat spinal muscular atrophy (SMA). The cost of gene therapy for now is prohibitive, although the manufacturers help with patient access. Zolgensma recently made headlines for its $2.1 million price tagand Luxturna for both eyes is about $850,000. The gene therapies, though, are intended to be one-and-done, or at least just in need of a booster. And the alternatives, in these two frontrunners, are blindness or death.

Given the cost of gene therapy and its restriction to genetic disruptions far simpler than the chaos of Aviyas chromosomes, its great that standard therapies are having an effect.

Shes been improving by leaps and bounds in everything, from how much she eats to what shes willing to try to her understanding of everything. Shes just so much better, since the PEG and beginning the special ed day care. She eats more, theres more variety to her food choices, and shes willing to try anything, Yosef said.

He knows that no research team or company is going to pursue a treatment for a sample size of one. What were doing is the best we can do. Its working, so if it aint broke dont fix it. If we find something else to do, then for sure well do it, but in the meantime, were doing the best that we figured out for now. Well see what the future holds.

So Ill end with a shout-out to the supportive therapies that help so many. Even after a sophisticated gene therapy that takes years, if not decades, to take to a clinical trial, supportive therapies are critical to maximizing any effect, on a daily basis. Perhaps no one knows that better than Lori Sames, whose daughter Hannah had gene therapy for giant axonal neuropathy in 2016. (See After Gene Therapy: Hannahs Journey Continues).

PT is incredibly important! When Hannah was a toddler and developed low muscle tone, our first sign something was wrong prior to her diagnosis, her first physical therapist emphasized how important it was to let her do everything. Do not pick her up and put her in her car seat. Open the door of the minivan and let her crawl in and hoist herself up into the car seat. Let her walk. If shes tired and asks to be carried for a bit, carry her for a bit. Keep her as active as you can for as long as you can.

Hannahs PT continues today. While standing, she does squats, leaning back as if shes sitting but powering back through to a stand before she touches the seat. Were trying to keep her hips and quads and hamstrings strong. We have her stand twice an hour and shes in the EasyStand device at least an hour a day. This is critically important for her internal organs and bone density, Lori recently told me.

Aviya is a wonderful, spirited child.

Shes a fun-loving, constantly happy kid, even though she has spent more time in the hospital then most people I know. Even while she was hospitalized she would always smile at the doctors and nurses and play with the other kids, with as much energy as she had. She loves taking things out of and putting them into bags or boxes. She loves hugging dolls and pretending to feed them. She loves playing outside with plants and watching ants going back and forth. She loves to be part of everything and to crawl around the house, and loves when people talk or sing to her and she talks and sings back, said her father.

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A Child's Shattered Chromosomes Illustrate the Value of Supportive Therapies | DNA Science Blog - PLoS Blogs

Good morning, everyone, and how are you today? We are doing just fine, thank you, courtesy of a warm and shiny sun and a delicious cool breeze wafting across the Pharmalot campus. Moreover, a soothing quietude has descended upon us now that our short person has left for the local schoolhouse and our official mascot has taken up his snoozing position in a faraway corner. As for us, yes, we are brewing our ritual cups of stimulation we favor hot-buttered rum today, for those keeping track. Meanwhile, here is the latest menu of interesting items for you. Hope you have a wonderful day and do keep in touch.

House Speaker Nancy Pelosi on Thursday formally unveiled her long-awaited plan to lower drug prices, giving Democrats an aggressive counter to the White Houses numerous and widely covered efforts to lower drug prices, STAT reports. The plan would enact an international price index, capping U.S. drug payments for Medicare at an average of foreign prices, and require the federal government to negotiate the cost of 250 prescription medicines, using the international price as a maximum price, and extend the negotiated price to insurers and the commercial market at large. The bill would also cap senior out-of-pocket drug expenses at $2,000 annually.

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Novartis says Pharmalittle: Pelosi unveils aggressive drug pricing plan - STAT