The collaboration agreed between the supply chain management services providers, McKesson and TrakCel, comes after the companies have jointly taken on the market entrance of a T-cell based allogeneic therapeutic product of an undisclosed late-stage biopharmaceutical developer.

The commercial launch of this product, which will be the first off-the-shelf product available, is expected in the fourth quarter of 2020, Akshay Peer, VP of sales and account management at TrakCel, told us.

Under the partnership and in order to serve this commercialization, as well as other future product launches, the two companies will develop a combined program, utilizing McKessons patient services alongside TrakCels data management software platform.

The special supply chain requirements of personalized treatments, such as cell and gene therapies, are due to the developers need to manage multiple players and organizations concurrently, according to Peer.

This includes different teams within site of care, shipping and logistics, manufacturing and storage, Peer added.

More specifically, according to TrakCels VP, the product journey consists of the below stations:

Layne Martin, VP of specialty distribution solutions at McKesson Life Sciences, commented that, as the wave of over 900 cell and gene products currently under review by the FDA come to market, supply chain service providers can begin to offer some standards to improve outcomes.

As the products evolve to the latest stages of development,a number of processes including patient scheduling and care have to be mapped, said Peer, adding that the case management teams that are in-charge of communicating with the patient and healthcare professionals need a dashboard view of the entire lifecycle development of the therapy.

According to the companies, the integrated platform is expected to enable the scale-up of products towards market delivery, for the increasing number of developers approaching the commercial launch of cell and gene therapies.

The platform will include automatic scheduling of product-specific workflows across multiple supply chain partners and care team members, and validated chain-of-identity tracking to guarantee correct drug product delivery.These capabilities ensure that the patient receives the correct, uncompromised treatment at the right time, McKesson stated.

Therefore, the integrated suite which will result from the collaboration is expected to provide a control tower view of the product distribution.

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TrakCel partners with McKesson - BioPharma-Reporter.com

The CharcotMarieTooth Association (CMTA) has granted $335,000 to two research projects focused on the development of new therapies for CharcotMarieTooth (CMT) disease type 1A, type 1B, and other demyelinating forms of CMT, including type 4.

CMTA has been funding projects for 30 years on research focused on discovering the mechanisms involved in CMT and on developing safe and effective therapies for the 2.8 million living with CMT worldwide.

The association launched its Strategy to Accelerate Research (STAR) initiative in 2008 to bring together scientists, pharmaceutical companies, and patients to create a multidisciplinary collaborative environment that would advance scientific and medical innovation in CMT.

CMTAsSTAR Advisory Board includes 30 leading scientists and clinicians who are responsible for analyzing the quality of ongoing projects and deciding which ones receive monetary support.

A grant totaling $154,000 was awarded to a collaboration project between three leading CMT experts Kleopas Kleopa, MD, PhD, from The Cyprus Institute of Neurology & Genetics; John Svaren, PhD, from the Waisman Center at the University of Wisconsin-Madison; and Steven Gray, PhD, from the University of Texas Southwestern Medical Center.

Their project will focus on the development of two different types of gene therapies. One therapy is designed to shut down the PMP22 gene, which is overactive in people with CMT1A. The second treatment candidate is designed to replace the defective genes responsible for the different forms of CMT4 and CMT1X.

The scientists will attempt to come up with safe viral vectors to deliver the modified versions of these genes to Schwann cells specialized cells that produce the fatty substance (myelin) protecting nerve cells which are defective in CMT.

The team is planning to test the efficacy of four different types of adeno-associated viruses (AAVs), developed by Gray, to determine the one that could better deliver the modified genes to Schwann cells in cases of CMT1A and CMT1X. The researchers will also test the efficacy of two AAVs in a mouse model of CMT1A.

The proposed experiments will seek to enable a translatable gene therapy approach for CMT1A, CMT1X, and various CMT4 forms. This will also be the first testing of AAV9 virus distribution to Schwann cells in a larger animal model (primate), the researchers said in their project proposal.

The second grant, which totaled $180,000, was awarded to a collaboration project between Maurizio DAntonio, PhD, from the IRCCS Ospedale San Raffaele and Ghjuvan Shackleford, PhD, from the Hunter James Kelly Research Institute.

Their project will focus on investigating the mechanisms of disease in a mouse model of late-onset CMT1B (named P0T124M) and discovering new therapeutic strategies to prevent the degeneration of nerve cells and their extensions (required for the proper transmission of nervous signals).

This project will identify signals and molecules that underlie glial support of axons, and could reveal new unifying therapeutic targets that are common to a large spectrum of neurodegenerative diseases, the researchers stated.

Joana is currently completing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. She also holds a BSc in Biology and an MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells cells that make up the lining of blood vessels found in the umbilical cord of newborns.

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CMTA Grants $335,000 to Projects that Advance Therapy Development - Charcot-Marie-Tooth News

Freeline has announced the dosing of the first patient in its MARVEL1 study, a multi-centre Phase I/II clinical trial of its liver-directed AAV gene therapy for Fabry Disease.

The study, which is the first clinical-stage adeno-associated virus (AAV) gene therapy study globally for Fabry Disease, leverages Freelines proprietary gene therapy platform, including its novel capsid, which has already shown clinical benefit for Haemophilia B patients.

The study aimed to deliver a replacement copy of the missing gene to the liver, which will then produce continuous high levels of GLA, offering the potential for therapy with a single treatment.

The initiation of the MARVEL1 study and dosing of the first patient is a significant milestone for Freeline, said Chris Hollowood, executive chairman of Freeline.

Continuous high expression of alpha GLA 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. With two programmes in the clinic on a common proprietary gene therapy platform, Freeline are building a leading systemic gene therapy company using next-generation AAV technology. These innovative gene therapies have the potential to change patients lives.

Fabry disease is a type of lysosomal storage disorder in which certain fatty molecules are not properly metabolised. Patients have a genetic mutation which leads to a deficiency of -galactosidase A enzyme (GLA) resulting in an accumulation of lipids, such as globotriaosylceramide (Gb3) and globotriaosylsphingosine (LysoGb3), throughout the body. This can cause highly debilitating progressive multi-organ disease.

It is estimated that Fabry Disease affects one in every 40,000 people. It is currently treated by enzyme replacement therapy (ERT), which requires regular and expensive infusions.

Link:

First patient dosed in Fabry Disease gene therapy trial - PharmaTimes

HACKENSACK, N.J., Sept. 17, 2019 /PRNewswire/ --Parent Project Muscular Dystrophy (PPMD), a nonprofit organization leading the fight to end Duchenne muscular dystrophy (Duchenne), announced plans to award H. Lee Sweeney, PhD, and his team at the University of Florida (Gainesville) $1 million to continue their exploration of developing novel therapies that can address the causes of dilated heart failure in Duchenne and Becker muscular dystrophy. This $1 million investment is part of PPMD's Cardiac Initiative and a direct result of the Duchenne community's generosity during the organization's 2018 end of the year campaign, as well as the support of other Duchenne families and foundations, including the Killian Family, Team Joseph, Kindness Over Muscular Dystrophy, Another Day for Gray Foundation, and Small Heroes Foundation.

Duchenne isthe most common fatal genetic disorder diagnosed in childhood, affecting approximately one in 5,000 live male births. Duchenne is caused by a change in the dystrophin gene. For people with Duchenne, cardiac disease is an area of great concern. The absence of dystrophin in the heart contributes to a progressive deterioration of cardiac muscle and eventual dilated cardiomyopathy (DCM) or heart disease.

Gene therapy, utilizing AAV vector as the delivery vehicle, provides a potential strategy to deliver transgenes targeting the mechanisms underlying the development of dilated cardiomyopathy. This funding supports the development of a heart specific therapy using an AAV vector containing two transgenes to restore calcium handling and prevent mitochondrial dysfunction. This therapy will potentially be able to treat the hearts of people living with Duchenne and Becker, in a way that is independent of, or complementary to, micro-dystrophin based gene therapy.

PPMD's Founding President and CEO, Pat Furlong, lost both of her sons to heart failure resulting from Duchenne, so this project is particularly meaningful to her and her family: "Heart issues don't just affect some people with Duchenne; they affect ALL people with Duchenne. And while we have improved cardiac care in Duchenne, we still need treatments that repair our children's hearts. Since our organization began 25 years ago, we have been asking questions and trying to better understand the effect of this disease on the heart. Chris and Patrick died of heart failure, so the heart is at the center of Duchenne for me. That's why I am extremely proud to announce this $1 million investment into a gene therapy with the potential to heal the hearts of our loved ones. I am grateful to Dr. Sweeney and the amazing team at University of Florida, as well as the families in our community who believe in our mission and gave generously to help fund the fight to end Duchenne."

Dr. Sweeney, who has a long history in Duchenne research and has worked with PPMD for over two decades, says that PPMD's funding comes at a critical moment in the development of gene therapy: "These are exciting times for gene therapies especially for gene therapies for Duchenne and Becker muscular dystrophy. However, while the current therapies may potentially help the skeletal muscles of patients, there is more to learn and to develop before we can be confident that we are doing all we can for the hearts of patients. The funds provided by PPMD will allow us to move faster toward the goal of creating the best possible gene therapy for the hearts of people with Duchenne and Becker."

Dilated cardiomyopathy (DCM) is the most common type of human cardiomyopathy, occurring mostly in adults 20 to 60. It affects the heart's ventricles and atria, the lower and upper chambers of the heart, respectively. Most forms of DCM are acquired forms from a number of causes that include coronary heart disease, heart attack, high blood pressure, diabetes, thyroid disease, viral hepatitis, and viral infections that inflame the heart muscle. In the case of certain forms of Becker, as well as in most cases of Duchenne, cardiomyopathy can ultimately limit the patient's survival.

While cardiomyopathy associated with Duchenne is technically a dilated cardiomyopathy that progresses to heart failure, many clinicians don't consider it a typical DCM because the patients' hearts don't tend to dilate until rather late in the disease progression. However, this is likely due to the fact that the hearts are not significantly burdened because of the patients' skeletal muscle disease and lack of ability to exercise.

Although Duchenne hearts do not dilate until late in disease progression, they get progressively stiff at earlier time points. This is clearly due to progressive fibrosis, and is slowed by the use of anti-fibrotic drugs, such as ACE inhibitors or ARBs (Angiotensin II Receptor Blockers). Interestingly, because of the fibrosis and lack of burden on the heart, the left ventricular chamber is actually smaller in diameter than normal after age 8 and until late in disease progression, when it begins to dilate. Again, consistent with this being related to the fibrosis is the fact the individuals who were not given ACE inhibitors early in disease progression show the smallest ventricular diameters and progress the fastest once they begin to dilate.

In the case of Becker, there clearly is a subset of Becker patients that show a disproportionately rapid progression of their cardiac disease as compared to their skeletal muscle disease. This has called attention to the fact that there are some regions of the dystrophin molecule that are more important in the heart than they are in skeletal muscle, likely because of components that differ in importance or even in identity between the heart and skeletal muscle.further explore a novel gene therapy approach that will target the heart in people living with Duchenne and Becker muscular dystrophy.

To learn more about PPMD's Cardiac Initiative, click here.

About Parent Project Muscular Dystrophy

Duchenneis a fatal genetic disorder that slowly robs people of their muscle strength. Parent Project Muscular Dystrophy (PPMD) is the largest most comprehensive nonprofit organization in the United States focused on finding a cure for Duchenneour mission is to end Duchenne.

We demand optimal care standards and strive to ensure every family has access to expert healthcare providers, cutting edge treatments, and a community of support. We invest deeply in treatments for this generation of Duchenne patients and in research that will benefit future generations. Our advocacy efforts have secured hundreds of millions of dollars in funding and won two FDA approvals.

Everything we doand everything we have done since our founding in 1994helps those with Duchenne live longer, stronger lives. We will not rest until we end Duchenne for every single person affected by the disease. Join our fight against Duchenne at EndDuchenne.org and follow PPMD on Facebook, Twitter, andYouTube.

SOURCE Parent Project Muscular Dystrophy

http://www.parentprojectmd.org

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PPMD Awards University of Florida $1 Million for Novel Gene Therapy Approach Targeting the Heart - PRNewswire

An early-stage update on Adverum Biotechnologies intravitreal gene therapy has triggered investor concern, after patients with wet age-related macular degeneration (AMD) saw their vision deteriorate, despite signs that the treatment is improving retinal anatomy.

Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

Over the six month period, patients did not require any anti-VEGF rescue injections and five of six patients saw a complete response with a total resolution of fluid following the Adverum injection. There were no serious adverse events, and the majority of side-effects were mild.

However, patients lost visual acuity by two letters on average, with a 90% confidence interval of -9.1 letters to +5.1 letters.

The range of individual patient data were not presented, though the wide confidence interval suggests that some patients may have experienced a loss of more than 10 letters during the course of the trial lack of rescue injections is difficult to square with declining vision. SVB Leerinks Mani Foroohar wrote in a note.

However, the study investigator insisted no loss in vision was due to wet AMD pathology and observed loss of visual acuity is due to normal variabilityin a small set of patients an assertion that, if proved out with additional follow-up, would very substantially improve the implied quality of this dataset.

Shares of the company which spectacularly failed years ago when it was christened Avalanche Biotechnologies $ADVM were down about 6.8% to $5.56 in Friday premarket trading. The stock sank on Thursday, evaporating millions from its market value.

This data suggest ADVM-022 is potentially active in delivering an expressible gene cassette in wet AMD, but mixed signals in this small dataset should lift some of the competitive overhang on RGNX shares, Foroohar added. RegenexBio experimental gene therapy for wet AMD, RGX-314, is currently in a Phase I/II trial.

Wet AMD, which is characterized by blurred vision or a blind spot in an individuals visual field, is typically caused by abnormal growth of blood vessels that leak fluid or blood into the macula. Macular degeneration is the leading cause of severe, irreversible vision loss in the elderly. Anti-VEGF injections such as Regenerons $REGN flagship Eylea, as well as Roches $RHBBY Lucentis and Avastin, are commonly used to treat wet AMD.

In April, the FDA imposed a clinical hold on an application to test ADVM-022 in humans, asking for additional data on Adverums chemistry, manufacturing and control process. In May, the hold was lifted. Late last year, the biotech abandoned its then lead experimental drug, ADVM-043, for the treatment of A1AT deficiency.

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Early snapshot of Adverum's eye gene therapy sparks concern about vision loss - Endpoints News

Prevail Therapeuticsis asking the U.S. Food and Drug Administration (FDA) to approved a request to open clinical trials, at higher doses than initially planned, into its investigational gene therapy PR001 in people with pediatric neuropathic Gauchers disease (type 2).

In its updated Investigational New Drug (IND) application, Prevail modified the original design of its clinical trial to allow for a higher starting dose of the therapy. This decision was based on conversations with the FDA and preclinical data supporting PR001 as a more effective and still safe treatment at higher doses, it announced in a press release.

The company is waiting on an FDA decision, and expects to start recruiting patients for a Phase 1/2 trial testing PR001 in children with neuropathic Gaucher in the first half of 2020. The IND, an essential step to opening a clinical study, was first filed in June.

We are dedicated to developing PR001 for pediatric nGD[neuropathic Gaucher disease], the most progressive form of Gaucher disease, which involves neurological manifestations that cause severe morbidity and mortality. We believe PR001 has tremendous potential to slow or stop disease progression in patients who currently have no disease-modifying therapeutic options, Asa Abeliovich, MD, PhD, founder, and CEO of Prevail, said in the release.

Gaucher disease is a hereditary condition caused by mutations in the GBA gene, which leads to the production of defective beta-glucocerebrosidase. This protein breaks down fatty molecules that are toxic if they accumulate inside the cells, leading to the array of symptomsassociated with Gauchers disease.

Toxic fatty molecules building in the brain lead to manifestations of neuropathic Gauchers, which can be observed from early infancy in type 2 disease.

PR001 uses a modified, harmless version of an adeno-associated virus (AAV9) to deliver a fullyworking copy of the GBA1 gene to nerve cells. This allows these cells to initiate processes that lead to the production of functional beta-glucocerebrosidase, which could ease the symptoms of neurotropic Gauchers disease. A single dose of PR001 has the potential to modify the disease with long-lasting effect.

Studies in mice and primatesfound that PR001 was well-tolerated and led to the expression of a functional protein in nerve cells, reducing the accumulation of fatty molecules and consequent symptoms.

AAV9 has been widely used to deliver gene therapies both in practice and in clinical trials. A transport vehicle for the corrected gene, it is engineered to be a harmless virus and can cross the blood-brain barrier, allowing it to reach nerve cells.

PR001 is also being developed and tested as a treatment of people with Parkinsons diseasewho have mutations in the GBA gene. Prevail has an open IND applicationfor trials here, and the therapy received fast-track designation by the FDA as a possible Parkinsons treatment.

Alejandra has a PhD in Genetics from So Paulo State University (UNESP) and is currently working as a scientific writer, editor, and translator. As a writer for BioNews, she is fulfilling her passion for making scientific data easily available and understandable to the general public. Aside from her work with BioNews, she also works as a language editor for non-English speaking authors and is an author of science books for kids.

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Ins Martins holds a BSc in Cell and Molecular Biology from Universidade Nova de Lisboa and is currently finishing her PhD in Biomedical Sciences at Universidade de Lisboa. Her work has been focused on blood vessels and their role in both hematopoiesis and cancer development.

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Type 2 Gaucher Trial of Gene Therapy PR001 May Open with Higher Dose - Gaucher Disease News

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A new gene therapy turns glial cellsabundant support cells in the braininto neurons, repairing damage that results from stroke and significantly improving motor function in mice.

Once researchers further develop the NeuroD1-based gene therapy, it could potentially help to treat stroke, which is a leading cause of disability in the US, with 800,000 new stroke patients every year.

The current treatment for stroke has a narrow time window, typically within a few hours after the occurrence of stroke, says lead author Yuchen Chen, a postdoctoral fellow at Penn State. Many patients cannot receive the treatment in time and as a result, often suffer from permanent disability caused by irreversible neuronal loss. There is an urgent need to develop a new therapy to regenerate new neurons and restore lost brain functions among stroke patients.

The human brain has approximately 86 billion neurons. While mini-strokes can be tolerated, moderate stroke involving the loss of billions of neurons leaves detrimental effects that do not spontaneously recover.

So, the critical question that is still unanswered in the neuroregeneration field is how can we regenerate billions of new neurons in a patients brain after stroke? says Gong Chen, professor of biology and chair in life sciences. The biggest obstacle for brain repair is that neurons cannot regenerate themselves. Many clinical trials for stroke have failed over the past several decades, largely because none of them can regenerate enough new neurons to replenish the lost neurons.

The reserchers pioneered a new approach to regenerate functional neurons using glial cells, a group of cells surrounding every single neuron in the brain that provide essential support to neurons. Unlike neurons, glial cells can divide and regenerate themselves, especially after brain injury.

I believe that turning glial cells that are already present in the brain into new neurons is the best way to replenish the lost neurons, says Gong Chen. These glial cells are the neighbors of the dead neurons in the brain and are likely to share the same ancestral cellular lineage.

The team previously reported that a single genetic neural factor, NeuroD1, could directly convert glial cells into functional neurons inside mouse brains with Alzheimers disease, but the total number of neurons generated was limited. The research team believed that this limited regeneration was due to the retroviral system used to deliver NeuroD1 to the brain.

In the current study, the research team used the AAV viral system, which is now the first choice for gene therapy in the nervous system, to deliver NeuroD1 into mouse motor cortex that a stroke had damaged.

Many neurons die after stroke but surviving glial cells can proliferate and form a glial scar in the stroke areas. The researchers designed their AAV system to express NeuroD1 preferentially in the glial cells that form these scars, turning them directly into neuronal cells. Such direct glia-to-neuron conversion technology not only increased neuronal density in the stroke areas, but also significantly reduced brain tissue loss the stroke caused.

Interestingly, the newly converted neurons showed similar neuronal properties to the neurons that were lost after stroke. This suggests a potential impact of the local glial lineage on the converted neuronal identity.

The most exciting finding of this study is to see the newly converted neurons being fully functional in firing repetitive action potentials and forming synaptic networks with other preexisting neurons, says Gong Chen. They also send out long-range axonal projections to the right targets and facilitate motor functional recovery.

A separate collaborative work led by Gregory Quirk, a professor at the University of Puerto Rico, further tested the NeuroD1-based gene therapy in a rat stroke model. Quirk and colleagues also found that this direct glia-to-neuron conversion technology can rescue cognitive functional deficits stroke induces.

Because glial cells are everywhere in the brain and can divide to regenerate themselves, our study provides the proof-of-concept that glial cells in the brain can be tapped as a fountain of youth to regenerate functional new neurons for brain repair not only for stroke but also for many other neurological disorders that result in neuronal loss, says Yuchen Chen. Our next step is to further test this technology and ultimately to translate it into clinically effective therapies to benefit millions of patients worldwide.

A paper describing the new therapy appears in the journal Molecular Therapy.

Additional researchers at Penn State and the University of Puerto Rico contributed to the work. The US National Institutes of Health and the Penn State Charles H. Skip Smith Endowment Fund supported the research.

Source: Penn State

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Therapy creates new neurons for faster stroke recovery - Futurity: Research News

Updated results from a Phase 2/3 clinical trial, Starbeam, evaluating bluebird bio's (BLUE -1.6%) gene therapy Lenti-D in patients with a rare severe inherited disorder called cerebral adrenoleukodystrophy (CALD) showed a sustained treatment effect. The data were presented at the European Pediatric Neurology Society Congress in Athens.

Treated patients remained free of major functional disabilities (MFDs) for as long as five years (and counting) with no reports of graft failure or treatment-related deaths. No new safety signals have been observed.

The study is assessing the safety and efficacy of autologous CD34+ hematopoietic stem cells transduced with Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein. In other words, stem cells are extracted from the patient, modified with Lenti-D, then infused back into the patient after myeloablative conditioning (bone marrow activity is intentionally decreased to reduce the risk of complications).

88% (n=15/17) of treated patients who reached or would have reached 24 months' follow-up and completed the study are still alive and MFD-free.

Development is ongoing.

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Bluebird gene therapy shows sustained benefit in CALD study - Seeking Alpha

Gene therapy, also called gene transfer therapy, introduction of a normal gene into an individuals genome in order to repair a mutation that causes a genetic disease. When a normal gene is inserted into the nucleus of a mutant cell, the gene most likely will integrate into a chromosomal site different from the defective allele; although that may repair the mutation, a new mutation may result if the normal gene integrates into another functional gene. If the normal gene replaces the mutant allele, there is a chance that the transformed cells will proliferate and produce enough normal gene product for the entire body to be restored to the undiseased phenotype.

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cancer: Gene therapy

Knowledge about the genetic defects that lead to cancer suggests that cancer can be treated by fixing those altered genes. One strategy

Human gene therapy has been attempted on somatic (body) cells for diseases such as cystic fibrosis, adenosine deaminase deficiency, familial hypercholesterolemia, cancer, and severe combined immunodeficiency (SCID) syndrome. Somatic cells cured by gene therapy may reverse the symptoms of disease in the treated individual, but the modification is not passed on to the next generation. Germline gene therapy aims to place corrected cells inside the germ line (e.g., cells of the ovary or testis). If that is achieved, those cells will undergo meiosis and provide a normal gametic contribution to the next generation. Germline gene therapy has been achieved experimentally in animals but not in humans.

Scientists have also explored the possibility of combining gene therapy with stem cell therapy. In a preliminary test of that approach, scientists collected skin cells from a patient with alpha-1 antitrypsin deficiency (an inherited disorder associated with certain types of lung and liver disease), reprogrammed the cells into stem cells, corrected the causative gene mutation, and then stimulated the cells to mature into liver cells. The reprogrammed, genetically corrected cells functioned normally.

Prerequisites for gene therapy include finding the best delivery system (often a virus, typically referred to as a viral vector) for the gene, demonstrating that the transferred gene can express itself in the host cell, and establishing that the procedure is safe. Few clinical trials of gene therapy in humans have satisfied all those conditions, often because the delivery system fails to reach cells or the genes are not expressed by cells. Improved gene therapy systems are being developed by using nanotechnology. A promising application of that research involves packaging genes into nanoparticles that are targeted to cancer cells, thereby killing cancer cells specifically and leaving healthy cells unharmed.

Some aspects of gene therapy, including genetic manipulation and selection, research on embryonic tissue, and experimentation on human subjects, have aroused ethical controversy and safety concerns. Some objections to gene therapy are based on the view that humans should not play God and interfere in the natural order. On the other hand, others have argued that genetic engineering may be justified where it is consistent with the purposes of God as creator. Some critics are particularly concerned about the safety of germline gene therapy, because any harm caused by such treatment could be passed to successive generations. Benefits, however, would also be passed on indefinitely. There also has been concern that the use of somatic gene therapy may affect germ cells.

Although the successful use of somatic gene therapy has been reported, clinical trials have revealed risks. In 1999 American teenager Jesse Gelsinger died after having taken part in a gene therapy trial. In 2000 researchers in France announced that they had successfully used gene therapy to treat infants who suffered from X-linked SCID (XSCID; an inherited disorder that affects males). The researchers treated 11 patients, two of whom later developed a leukemia-like illness. Those outcomes highlight the difficulties foreseen in the use of viral vectors in somatic gene therapy. Although the viruses that are used as vectors are disabled so that they cannot replicate, patients may suffer an immune response.

Another concern associated with gene therapy is that it represents a form of eugenics, which aims to improve future generations through the selection of desired traits. Some have argued that gene therapy is eugenic but that it is a treatment that can be adopted to avoid disability. To others, such a view of gene therapy legitimates the so-called medical model of disability (in which disability is seen as an individual problem to be fixed with medicine) and raises peoples hopes for new treatments that may never materialize.

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Gene therapy | medicine | Britannica.com

Could the condition be corrected by adding one or a few functional genes?For you to even consider gene therapy, the answer must be "yes." For instance, genetic disorders caused by mutations in single genes tend to be good candidates for gene therapy, while diseases involving many genes and environmental factors tend to be poor candidates.

Do you know which genes are involved?If you plan to treat a genetic flaw, you need to know which gene(s) to pursue. You must also have a DNA copy of the gene available in your laboratory.

Do you understand the biology of the disorder?To design the best possible approach, you need to learn all you can about how the gene factors into the disorder. For example, which tissues the disorder affects, what role the protein encoded by the gene plays within the cells of that tissue, and exactly how mutations in the gene affect the protein's function.

Will adding a normal copy of the gene fix the problem in the affected tissue? Or could getting rid of the defective gene fix it?Sometimes when a gene is defective, no functional protein is being made from it. In cases like these, adding a functional copy of the gene could correct the problem. But sometimes a defective gene codes for a protein that starts doing something it shouldn't or prevents another protein from doing its job. In order to correct the problem, you would need to get rid of the misbehaving protein.

Can you deliver the gene to cells of the affected tissue?The answer will come from several pieces of information, including the tissue's accessibility and molecular signatures.

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What is Gene Therapy? - Learn.Genetics

Collaboration between Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital. Clinical research in the areas of stem cell transplantation, cellular therapy, and gene therapy.

The Center fosters a multidisciplinary approach to new research as well as collaborative research endeavors in the area of gene therapy. The Vector Core manufactures several recombinant viral vectors.

The research is focused on various aspects of gene therapy, such as understanding basic virology, efficient gene delivery into the nucleus of cells, and incorporation of these genes into the genome.

Research in the laboratory has centered on the molecular biology of adeno-associated virus (AAV) in order to exploit the unique features of this virus to develop an efficient viral vector system for use in human gene therapy.

The Harvard Gene Therapy Initiative is headed by Dr. Richard Mulligan with the objective of promoting the use of gene therapy and to conduct research developing new gene delivery vector technologies.

Diseases of the lung, cardiovascular system, muscles, brain, and skin are focus areas of research as well as the development of gene therapy vectors and the identification of disease-causing genes.

A multidisciplinary team of scientists and physicians work together to realize the full potential of virus, gene and cell therapies from basic science discovery to clinical translation.

Oncolytic virotherapy, gene therapy for diabetes and cardiovascular diseases, virus-based gene therapy vectors.

The program has brought together regulatory, quality, product development, manufacturing and facilities engineering expertise to enable the translation of novel, experimental research into medicine for use in human clinical trials.

Penn Vector offers a variety of services associated with the development and production of both non-viral vectors and viral vectors including those derived from adeno-associated virus (AAV), adenovirus, and lentivirus.

The primary mission is to merge molecular genetics research and health care delivery by developing new therapeutic strategies for the treatment of human diseases that involve gene transfer.

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Gene Therapy Research Institutes and Universities

Gene therapy is an experimental technique that aims to treat genetic diseases by altering a disease-causing gene or introducing a healthy copy of a mutated gene to the body. The U.S. Food and Drug Administrationapprovedthe first gene therapy for an inherited disease a genetic form of blindness in December 2017.

Sickle cell anemia is caused by a mutation in the HBB gene which provides the instructions to make part of hemoglobin, the protein in red blood cells that carries oxygen.

Researchers are working on two different strategies to treat sickle cell anemia with gene therapy. Both of these strategies involve genetically altering the patients own hematopoietic stem cells. These are cells in the bone marrow that divide and specialize to produce different types of blood cells, including the red blood cells.

One strategy is to remove some of the patients hematopoietic stem cells, replace the mutated HBB gene in these cells with a healthy copy of the gene, and then transplant those cells back into the patient. The healthy copy of the gene is delivered to the cells using a modified, harmless virus. These genetically corrected cells will then hopefully repopulate the bone marrow and produce healthy, rather than sickled, red blood cells.

The other strategy is to genetically alter another gene in the patients hematopoietic stem cells so they boost production of fetal hemoglobin a form of hemoglobin produced by babies from about seven months before birth to about six months after birth. This type of hemoglobin represses sickling of cells in patients with sickle cell anemia, but most people only produce a tiny amount of it after infancy. Researchers aim to increase production of fetal hemoglobin in stem cells by using a highly specific enzyme to cut the cells DNA in the section containing one of the genes that suppress production of fetal hemoglobin. When the cell repairs its DNA, the gene no longer works and more fetal hemoglobin is produced.

Gene therapy offers an advantage over bone marrow transplant, in that complications associated with a bone marrow donation now the only cure for the disease such as finding the right match are not a concern.

Twelve clinical trials studying gene therapy to treat sickle cell anemia are now ongoing. Nine of the 12 are currently recruiting participants.

Four trials (NCT02186418, NCT03282656, NCT02247843, NCT02140554) are testing the efficacy and safety of gene therapy to replace the mutated HBB gene with a healthy HBB gene. These Phase 2 trials are recruiting both children and adults in the United States and Jamaica.

Three trials (NCT02193191, NCT02989701, NCT03226691) are investigating the use ofMozobil (plerixafor) in patients with sickle cell anemia to increase the production of stem cells to be used for gene therapy. This medication is already approved to treat certain types of cancer. All three are recruiting U.S. participants.

One trial (NCT00669305) is recruiting sickle cell anemia patients in Tennessee to donate bone marrow to be used in laboratory research to develop gene therapy techniques.

The final study(NCT00012545) is examining the best way to collect, process and store umbilical cord blood from babies with and without sickle cell anemia. Cord blood contains abundant stem cells that could be used in developing gene therapy for sickle cell anemia. This trial is open to pregnant women in Maryland both those who risk having an infant with sickle cell anemia, and those who do not.

One clinical trial (NCT02151526) conducted in France is still active but no longer recruiting participants. It is investigating the efficacy of gene therapy in seven patients. For the trial, a gene producing a therapeutic hemoglobin that functions similarly to fetal hemoglobin is introduced into the patients stem cells. A case studyfrom one of the seven was published in March 2017; it showed that the approach was safe and could be an effective treatment option for sickle cell anemia.

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Sickle Cell Anemia News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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Gene Therapy - Sickle Cell Anemia News

Patients cant wait, and neither will we

At Axovant, we operate with a sense of urgency to develop and deliver innovative gene therapies that transform the treatment of serious neurological and neuromuscular diseases. In this critical journey, we are inspired by breakthrough science and driven to challenge the status quo on behalf of patients and their families. By harnessing the transformative power of gene therapies, our aim is to fill their unmet medical needs with one-time therapies that deliver lifelong benefits.

Axovant is an agile organization with a sharp focus on the rapid delivery of lasting, transformative gene therapies. Our decision-making is guided by our compassion for patients and their urgent need for better solutions. To that end, we approach gene therapy development by selecting the product candidates that have great potential for transformative impact. We continue to tailor these therapies to precisely address the needs of the diseases and patients we serve. Our agile operations and leading manufacturing partnerships enable us to meet our goals for rapid clinical execution.

We have assembled a leadership team of the foremost experts in gene therapy development, manufacturing and commercialization. Our growing team is committed to answering the call of patients and has proven expertise in driving scientific breakthroughs into the clinic, navigating the regulatory environment, and ensuring patients have access to life-saving therapies. For us, every day matters because every life matters.

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About Us | Axovant Gene Therapies

They were born without a working germ-fighting system, every infection a threat to their lives. Now eight babies with "bubble boy disease" have had it fixed by a gene therapy made from one of the immune system's worst enemies HIV, the virus that causes AIDS.

Astudyout Wednesday details how scientists turned this enemy virus into a savior, altering it so it couldn't cause disease and then using it to deliver a gene the boys lacked.

"This therapy has cured the patients," although it will take more time to see if it's a permanent fix, said Dr. Ewelina Mamcarz, one of the study leaders at St. Jude Children's Research Hospital in Memphis.

Omarion Jordan, who turns 1 later this month, had the therapy in December to treat severe combined immunodeficiency syndrome, or SCID.

"For a long time we didn't know what was wrong with him. He just kept getting these infections," said his mother, Kristin Simpson. Learning that he had SCID "was just heartbreaking ... I didn't know what was going to happen to him."

Omarion now has a normal immune system. "He's like a normal, healthy baby," Simpson said. "I think it's amazing."

Study results were published by the New England Journal of Medicine. The treatment was pioneered by a St. Jude doctor who recently died, Brian Sorrentino.

SCID is caused by a genetic flaw that keeps the bone marrow from making effective versions of blood cells that comprise the immune system. It affects 1 in 200,000 newborns, almost exclusively males. Without treatment, it often kills in the first year or two of life.

"A simple infection like the common cold could be fatal," Mamcarz said.

The nickname "bubble boy disease" comes from a famous case in the 1970s a Texas boy who lived for 12 years in a protective plastic bubble to isolate him from germs. A bone marrow transplant from a genetically matched sibling can cure SCID, but most people lack a suitable donor. Transplants also are medically risky the Texas boy died after one.

Doctors think gene therapy could be a solution. It involves removing some of a patient's blood cells, using the modified HIV to insert the missing gene, and returning the cells through an IV. Before getting their cells back, patients are given a drug to destroy some of their marrow so the modified cells have more room to grow.

When doctors first tried it 20 years ago, the treatment had unintended effects on other genes, and some patients later developed leukemia. The new therapy has safeguards to lower that risk.

A small study of older children suggested it was safe. The new study tried it in infants, and doctors are reporting on the first eight who were treated at St. Jude and at UCSF Benioff Children's Hospital San Francisco.

Within a few months, normal levels of healthy immune system cells developed in seven boys. The eighth needed a second dose of gene therapy but now is well, too. Six to 24 months after treatment, all eight are making all the cell types needed to fight infections, and some have successfully received vaccines to further boost their immunity to disease.

No serious or lasting side effects occurred.

Omarion is the 10th boy treated in the study, which is ongoing. It's sponsored by the American Lebanese Syrian Associated Charities, the California Institute of Regenerative Medicine, the Assisi Foundation of Memphis and the federal government.

"So far it really looks good," but patients will have to be studied to see if the results last, said Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, which helped develop the treatment. "To me, this looks promising."

Rights to it have been licensed by St. Jude to Mustang Bio. Doctors say they have no estimate on what it might cost if it does become an approved treatment.

A similar technique harnessing a modified version of HIV is also being studied as a possible cure for sickle cell anemia, CBS News chief medical correspondent Dr. Jon LaPook reports. In a clinical trial at the National Institutes of Health, nine adults with sickle cell anemia have undergone the gene therapy. So far, all are responding well.

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Gene therapy might be a cure for "bubble boy disease ...

News Release

Wednesday, April 17, 2019

NIH scientists and funding contributed to development of experimental treatment

A small clinical trial has shown that gene therapy can safely correct the immune systems of infants newly diagnosed with a rare, life-threatening inherited disorder in which infection-fighting immune cells do not develop or function normally. Eight infants with the disorder, called X-linked severe combined immunodeficiency (X-SCID), received an experimental gene therapy co-developed by National Institutes of Health scientists. They experienced substantial improvements in immune system function and were growing normally up to two years after treatment. The new approach appears safer and more effective than previously tested gene-therapy strategies for X-SCID.

These interim results from the clinical trial, supported in part by NIH, were published today in The New England Journal of Medicine.

Infants with X-SCID, caused by mutations in the IL2RG gene, are highly susceptible to severe infections. If untreated, the disease is fatal, usually within the first year or two of life. Infants with X-SCID typically are treated with transplants of blood-forming stem cells, ideally from a genetically matched sibling. However, less than 20% of infants with the disease have such a donor. Those without a matched sibling typically receive transplants from a parent or other donor, which are lifesaving, but often only partially restore immunity. These patients require lifelong treatment and may continue to experience complex medical problems, including chronic infections.

"A diagnosis of X-linked severe combined immunodeficiency can be traumatic for families," said Anthony S. Fauci, M.D., director of NIHs National Institute of Allergy and Infectious Diseases (NIAID). These exciting new results suggest that gene therapy may be an effective treatment option for infants with this extremely serious condition, particularly those who lack an optimal donor for stem cell transplant. This advance offers them the hope of developing a wholly functional immune system and the chance to live a full, healthy life.

To restore immune function to those with X-SCID, scientists at NIAID and St. Jude Childrens Research Hospital in Memphis, Tennessee, developed an experimental gene therapy that involves inserting a normal copy of the IL2RG gene into the patients own blood-forming stem cells. The Phase 1/2 trial reported today enrolled eight infants aged 2 to 14 months who were newly diagnosed with X-SCID and lacked a genetically matched sibling donor. The study was conducted at St. Jude and the Benioff Childrens Hospital of the University of California, San Francisco. Encouraging early results from a separate NIAID-led study at the NIH Clinical Center informed the design of the study in infants. The NIH study is evaluating the gene therapy in older children and young adults with X-SCID who previously had received stem cell transplants.

The gene therapy approach involves first obtaining blood-forming stem cells from a patients bone marrow. Then, an engineered lentivirus that cannot cause illness is used as a carrier, or vector, to deliver the normal IL2RGgene to the cells. Finally, the stem cells are infused back into the patient, who has received a low dose of the chemotherapy medication busulfan to help the genetically corrected stem cells establish themselves in the bone marrow and begin producing new blood cells.

Normal numbers of multiple types of immune cells, including T cells, B cells and natural killer (NK) cells, developed within three to four months after gene therapy in seven of the eight infants. While the eighth participant initially had low numbers of T cells, the numbers greatly increased following a second infusion of the genetically modified stem cells. Viral and bacterial infections that participants had prior to treatment resolved afterwards. The experimental gene therapy was safe overall, according to the researchers, although some participants experienced expected side effects such as a low platelet count following chemotherapy.

"The broad scope of immune function that our gene therapy approach has restored to infants with X-SCID as well as to older children and young adults in our study at NIH is unprecedented," said Harry Malech, M.D., chief of the Genetic Immunotherapy Section in NIAIDs Laboratory of Clinical Immunology and Microbiology. Dr. Malech co-led the development of the lentiviral gene therapy approach with St. Judes Brian Sorrentino, M.D., who died in late 2018. These encouraging results would not have been possible without the efforts of my good friend and collaborator, the late Brian Sorrentino, who was instrumental in developing this treatment and bringing it into clinical trials, said Dr. Malech.

Compared with previously tested gene-therapy strategies for X-SCID, which used other vectors and chemotherapy regimens, the current approach appears safer and more effective. In these earlier studies, gene therapy restored T cell function but did not fully restore the function of other key immune cells, including B cells and NK cells. In the current study, not only did participants develop NK cells and B cells, but four infants were able to discontinue treatment with intravenous immunoglobulins infusions of antibodies to boost immunity. Three of the four developed antibody responses to childhood vaccinations an indication of robust B-cell function.

Moreover, some participants in certain early gene therapy studies later developed leukemia, which scientists suspect was because the vector activated genes that control cell growth. The lentiviral vector used in the study reported today is designed to avoid this outcome.

Researchers are continuing to monitor the infants who received the lentiviral gene therapy to evaluate the durability of immune reconstitution and assess potential long-term side effects of the treatment. They also are enrolling additional infants into the trial. The companion NIH trial evaluating the gene therapy in older children and young adults also is continuing to enroll participants.

The gene therapy trial in infants is funded by the American Lebanese Syrian Associated Charities (ALSAC), and by grants from the California Institute of Regenerative Medicine and the National Heart, Lung, and Blood Institute, part of NIH, under award number HL053749. The work also is supported by NIAID under award numbers AI00988 and AI082973, and by the Assisi Foundation of Memphis. More information about the trial in infants is available on ClinicalTrials.gov using identifier NCT01512888. More information about the companion trial evaluating the treatment in older children and young adults is available using ClinicalTrials.gov identifier NCT01306019.

NIAID conducts and supports research at NIH, throughout the United States, and worldwide to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

E Mamcarz et al. Lentiviral gene therapy with low dose busulfan for infants with X-SCID. The New England Journal of Medicine DOI: 10.1056/NEJMoa1815408 (2019).

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Gene therapy restores immunity in infants with rare ...

A change or damage to a gene can affect the message the gene carries, and that message could be telling our cells to make a specific protein that the body needs in order to function properly. NAV Gene Therapy focuses on correcting these defects in genetic diseases by delivering a healthy, working copy of the gene to the cells in need of repair, which potentially enables the body to make the deficient protein. The NAV Technology Platform can also be used to deliver a gene that allows the body to produce a therapeutic protein to treat a specific disease.

Heres how the NAV Technology Platform works:

First, our scientists insert the gene of interest (that is, either the missing/defective gene or a gene to create a therapeutic protein) into a NAV Vector. A NAV Vector is a modified adeno-associated virus (AAV), which is not known to cause disease in humans. It is common for viruses to be used as vectors in gene and cell therapy. The NAV Vector acts as a delivery vehicle, transporting and unloading the gene into cells where the gene triggers production of the protein the body needs.

Our NAV Technology Platform includes more than 100 novel AAV vectors, including AAV8, AAV9 and AAVrh10, many of which are tailored to reach specific areas of the body where the gene is needed most. For example, gene therapy delivered to the liver has the potential to treat metabolic diseases like hemophilia, whereas gene therapy designed to reach the central nervous system (brain and spinal cord) may primarily impact symptoms of diseases that affect the brain and cognition.

Next, the NAV Vector is administered into the patient by injection or infusion, and is expected to make its way to cells that need the protein. The NAV Vector is designed to reach the target cells and deliver the gene it is carrying, enabling the cells to make the protein the body needs. These genes have the potential to correct disease by triggering production of a therapeutic protein or by allowing the bodys natural mechanisms to work the way they were intended.

Because gene therapies may have a long-term effect, a single administration of NAV Gene Therapy has the potential to do the same work as years of conventional chronic therapies.

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Gene Therapy - REGENXBIO

Gene therapy is a technology aimed at correcting or fixing a gene that may be defective. This exciting and potentially transformative area of research is focused on the development of potential treatments for monogenic diseases, or diseases that are caused by a defect in one gene.

The technology involves the introduction of genetic material (DNA or RNA) into the body, often through delivering a corrected copy of a gene to a patients cells to compensate for a defective one, using a viral vector.

The technology involves the introduction of genetic material (DNA or RNA) into the body, often through delivering a corrected copy of a gene to a patients cells to compensate for a defective one, using a viral vector.

Viral vectors can be developed using adeno-associated virus (AAV), a naturally occurring virus which has been adapted for gene therapy use. Its ability to deliver genetic material to a wide range of tissues makes AAV vectors useful for transferring therapeutic genes into target cells. Gene therapy research holds tremendous promise in leading to the possible development of highly-specialized, potentially one-time delivery treatments for patients suffering from rare, monogenic diseases.

Pfizer aims to build an industry-leading gene therapy platform with a strategy focused on establishing a transformational portfolio through in-house capabilities, and enhancing those capabilities through strategic collaborations, as well as potential licensing and M&A activities.

We're working to access the most effective vector designs available to build a robust clinical stage portfolio, and employing a scalable manufacturing approach, proprietary cell lines and sophisticated analytics to support clinical development.

In addition, we're collaborating with some of the foremost experts in this field, through collaborations with Spark Therapeutics, Inc., on a potentially transformative gene therapy treatment for hemophilia B, which received Breakthrough Therapy designation from the US Food and Drug Administration, and 4D Molecular Therapeutics to discover and develop targeted next-generation AAV vectors for cardiac disease.

Gene therapy holds the promise of bringing true disease modification for patients suffering from devastating diseases, a promise were working to seeing become a reality in the years to come.

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What is Gene Therapy? | Pfizer: One of the world's premier ...

Virtually all cells in the human body contain genes, making them potential targets for gene therapy. However, these cells can be divided into two major categories: somatic cells (most cells of the body) or cells of the germline (eggs or sperm). In theory it is possible to transform either somatic cells or germ cells.

Gene therapy using germ line cells results in permanent changes that are passed down to subsequent generations. If done early in embryologic development, such as during preimplantation diagnosis and in vitro fertilization, the gene transfer could also occur in all cells of the developing embryo. The appeal of germ line gene therapy is its potential for offering a permanent therapeutic effect for all who inherit the target gene. Successful germ line therapies introduce the possibility of eliminating some diseases from a particular family, and ultimately from the population, forever. However, this also raises controversy. Some people view this type of therapy as unnatural, and liken it to "playing God." Others have concerns about the technical aspects. They worry that the genetic change propagated by germ line gene therapy may actually be deleterious and harmful, with the potential for unforeseen negative effects on future generations.

Somatic cells are nonreproductive. Somatic cell therapy is viewed as a more conservative, safer approach because it affects only the targeted cells in the patient, and is not passed on to future generations. In other words, the therapeutic effect ends with the individual who receives the therapy. However, this type of therapy presents unique problems of its own. Often the effects of somatic cell therapy are short-lived. Because the cells of most tissues ultimately die and are replaced by new cells, repeated treatments over the course of the individual's life span are required to maintain the therapeutic effect. Transporting the gene to the target cells or tissue is also problematic. Regardless of these difficulties, however, somatic cell gene therapy is appropriate and acceptable for many disorders, including cystic fibrosis, muscular dystrophy, cancer, and certain infectious diseases. Clinicians can even perform this therapy in utero, potentially correcting or treating a life-threatening disorder that may significantly impair a baby's health or development if not treated before birth.

In summary, the distinction is that the results of any somatic gene therapy are restricted to the actual patient and are not passed on to his or her children. All gene therapy to date on humans has been directed at somatic cells, whereas germline engineering in humans remains controversial and prohibited in for instance the European Union.

Somatic gene therapy can be broadly split into two categories:

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Gene Therapy Technology Explanied

Gene therapy, the use of genetic material to treat a disease or disorder, is making strides in muscular dystrophy. Although the approach is still considered experimental, studies in animal models have shown promising results and clinical trials in humans are underway.

Gene therapy has the potential to help people with inherited disorders, in which a gene mutation causes cells to produce a defective protein or no protein at all, leading to disease symptoms.

To deliver the genetic material to the cells, scientists use a tool called a vector. This is typically a virus that has been modified so that it doesnt cause disease. It is hoped that the vector will carry the therapeutic gene into the cells nucleus, where it will provide the instructions necessary to make the desired protein.

The most common form of muscular dystrophy, Duchenne muscular dystrophy, is caused by a mutation in the DMD gene, which codes for a protein called dystrophin. Dystrophin is part of a protein complex that strengthens and protects muscle fibers. When the cells dont have functional dystrophin due to the gene mutation, muscles progressively weaken. Scientists think that supplying a gene that codes for a functional form of dystrophin might be an effective treatment for Duchenne muscular dystrophy.

Using gene therapy to deliver a correct form of the dystrophin gene has been challenging because of the size of the DMD gene, which is the largest gene in the human genome so it does not fit into commonly used vectors.

Scientists are having more success with a shortened version of the DMD gene that produces a protein called micro-dystrophin. Even though its a smaller version of dystrophin, micro-dystrophin includes key elements of the protein and is functional.

Administering a gene for micro-dystrophin to golden retriever dogs that naturally develop muscular dystrophy showed promising results in a study published in July 2017. Muscular dystrophy symptoms were reduced for more than two years following the treatment and the dogs muscle strength improved. The gene was delivered using a recombinant adeno-associated virus, or rAAV, as the vector.

A similar therapy is now being tested in people in a Phase 1/2 clinical trial (NCT03375164)at Nationwide Childrens Hospital in Columbus, Ohio. A single dose of the gene therapytreatment containing the gene encoding for micro-dystrophinwill be infused into the blood system of 12 patients in two age groups: 3 months to 3 years, and 4 to 7 years. The first patient in the trial, which is recruiting participants, already has received the treatment, according to a January 2018 press release.

The biopharmaceutical company Sarepta Therapeutics is contributing funding and other support to the project.

Sarepta is developing another potential gene therapy for Duchenne muscular dystrophy where rather than targeting the DMD gene that codes for dystrophin, the therapy will be used to try to increase the expression of a gene called GALGT2. The overproduction of this gene is thought to produce changes in muscle cell proteins that strengthen them and protect them from damage, even in the absence of functional dystrophin.

A Phase 1/2a clinical trial (NCT03333590) was launched in November 2017 at Nationwide Childrens Hospital for the therapy, called rAAVrh74.MCK.GALGT2.

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Muscular Dystrophy Newsis strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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Gene Therapy in Muscular Dystrophy - Muscular Dystrophy News

Gene therapy has been studied for more than 40 years and can help stop or slow the effects of disease on the most basic level of the human bodyour genes. And to understand how it works, well start at the basics.

Genes are made up of DNA, which are blueprints to build enzymes and proteins that make our body work. As far as we know, humans have between 20,000 and 25,000 genes. We typically get two copies of each gene from our parents. They influence everything from the color of our hair to our immune system, but genes arent always built correctly. A small adjustment to them can change how our proteins work, which then alter the way we breathe, walk or even digest food. Genes can change as they go through inherited mutations, as they age, or by being altered or damaged by chemicals and radiation.

In the case that a gene changesalso known as mutatingin a way that causes disease, gene therapy may be able to help. Gene therapy is the introduction, removal or change in genetic materialspecifically DNA or RNAinto the cells of a patient to treat a specific disease. The transferred genetic material changes how a proteinor group of proteinsis produced by the cell.

This new genetic material or working gene is delivered into the cell by using a vector. Typically, viruses are used as vectors because they have evolved to be very good at sneaking into and infecting cells. But in this case, their motive is to insert the new genes into the cell. Some types of viruses being used are typically not known to cause disease and other times the viral genes known to cause disease are removed. Regardless of the type, all viral vectors are tested many times for safety prior to being used. The vector can either be delivered outside the body (ex-vivo treatment) or the vectors can be injected into the body (in-vivo treatment).

Other types of drugs are typically used to manage disease or infection symptoms to relieve pain, while gene therapy targets the cause of the disease. It is not provided in the form of a pill, inhalation or surgery, it is provided through an injection or IV.

What Counts as a Rare Disease?

Gene therapy treats diseases in patients that are rare and often life threatening. Rare is defined as any disease or disorder affecting fewer than 200,000 people in the U.S. by the National Institutes of Health. As of now, there are around 7,000 rare diseases, affecting a total of approximately one in ten people. Many of these rare diseases are caused by a simple genetic mutation inherited from one or both parents.

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Which Diseases Have Gene Therapies?

Of gene therapies up for approval over the next five years, 45 percent are anticipated to focus on cancer treatments and 38 percent are expected to treat rare inherited genetic disorders. Gene therapy can help add to or change non-functioning genescreating a great opportunity to assist with rare inherited disorders, which are passed along from parents. The mutation might be present on one or both chromosomes passed along to the children. The majority of gene therapies are currently being studied in clinical trials.

Some of these inherited diseases include (but are not limited to):

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Why Do We Use Viral Vectors?

As you know from cold and flu season, viruses are quite skilled in the art of invading our bodiesadding their genetic material into our cells. However, researchers have learned to harness this sneaky ability to our advantage. Viruses are often used as a vehicle to deliver good genes into our cells, as opposed to the ones that cause disease.

Viruses are sometimes modified into vectors as researchers remove disease-causing material and add the correct genetic material. In gene therapy, researchers often use adeno-associated viruses (AAV) as vectors. AAV is a small virus that isnt typically known to cause disease in the first place, significantly reducing a chance of a negative reaction.

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Gene Therapy Basics | Education | ASGCT American Society ...