Category Archives: Gene Medicine

As companies like 23andMe and Ancestry.com help make genetic testing commonplace, you would think that we would become better at ensuring protections for the privacy of that data. Instead, multiple Congressional actions threaten to erode already-weak protections against genetic discrimination. But its not just a dystopian Gattaca future where citizens are discriminated against based on their genes that we need to be worried aboutone researcher is concerned that our inadequate genetic privacy laws will stymy science.

Its inhibiting both clinical care and research, Robert Green, a medical geneticist at Harvard Medical School, told Gizmodo.

Greens work focuses on how genomic medicine impacts peoples health and behavior. One thing hes particularly interested in is what makes people inclined to say yes to a genetic test. And hes observed one particularly big reason why people seem to be saying no: fears of genetic discrimination.

For Green and other geneticists, that makes their work harder to doresearch to, say, track how a particular gene affects a certain condition requires thousands of people to undergo genome sequencing, and the harder it is to attract those numbers, the longer it takes to do the work. Ultimately, this could mean treatments taking more time to get to patients.

But fears of genetic discrimination could also impact the health of those patients directly, if they refuse testing that could help doctors treat them.

People are concerned that if they find theyre carrying a risky gene and it goes into their medical record, it will have a bad impact in some way, Green said. Which they should be.

In 2008, Congress passed the Genetic Information and Nondiscrimination Act,(or GINA) to prohibit health insurers and employers from either requiring genetic testing or using it in making decisions about things like deductibles. The protections of GINA already do not apply to life insurance, long-term care, or disability insurance, meaning those companies are free to ask for genetic information and reject people deemed too risky. The Affordable Care Act, now in the midst of being replaced, solved another problem with GINA, protecting against discrimination for preexisting conditions revealed via genetic tests. Another bill, HR1313, currently under review in the House, would allow employers to request that employees undergo genetic testing, with the risk of paying hefty fines if they refuse.

Were injecting terrible opportunities for discrimination into the workplace, Green said.

Green has just started looking at how this impacts health care and research outcomes. In one project, early data suggests the impact may be significant.

As part of a major NIH-funded study looking at how genetic sequencing of infants impact health care, Green and his colleagues offered the parents of more than 2,500 newborns free genetic sequencing for their child. Of those, parents of 325 newborns agreed to attend an information session. Only 57 wound up participating.

Greens group is continuing to research why parents say yes or no to genetic testing. So far, Green tells Gizmodo, his investigation has revealed that privacy concerns play a role, possible a major one.

People decline genetic tests because of concerns over privacy and genetic discrimination, especially insurance discrimination, he said. This is stymying biomedical research and peoples access to healthcare.

While many are frustrated by inadequate genetic privacy protections, insurers and employers argue that theres a business reason for revealing genetic information. With more information on the risks of covering patients, insurers might be able to offer a more affordable, efficient product.

Green said that the UK offers a good example of how the US might approach its problem. There, insurers and the government have reached an agreement that both guarantees the right to insurance, and the rights of insurers to access information that may impact risk. The agreement states that insurers must establish a higher bar than typical when basing risk assessment on genetic testing data. In other words, they cant see that youre a carrier for a gene that might lead you to develop a disease, and immediately treat that gene as a preexisting condition. It also ensures consumers cant be pressured into taking a test, that tests taken in the course of medical research are exempt from being shared with insurers, and that people cant be asked to share the genetic testing information of relatives.

There are ways can we satisfy business needs of companies and also satisfy the privacy of consumers, Green said. But right now, we in the genetics community are actually aghast.

Excerpt from:
Are Our Terrible Genetic Privacy Laws Hurting Science? - Gizmodo

Sacramento Bee

Will this gene-editing tool cure the diseases of the future? Sacramento Bee We delete the gene, and we investigate what changes in behavior or physiology are the result of the deletion of that gene, Wood said. The results are being compared against human medical records, and this will find potential new models and sources ...

View original post here:
Will this gene-editing tool cure the diseases of the future? - Sacramento Bee

by: Action News Jax Updated: May 22, 2017 - 8:04 PM

Action News Jax has learned about a revolutionary medical breakthrough that wouldn't have been possible without the help of a former Jacksonville Jaguar and his wife.

A new gene-replacement therapy treatment could unlock the means to cure a devastating type of muscular dystrophy. It's already saved the lives of dogs and is just months away from being tested in children.

Video shows dogs that were destined to die, showing no signs of the disease after a single infusion of gene-replacement therapy. The disease is so deadly in children, 50 percent of them die before their second birthday.

"This is a huge deal. This is probably the most important thing we'll ever work on," said Dr. Casey Childers of the University of Washington Medicine.

For the past eight years, Childers has been focused on finding a cure for a form of muscular dystrophy called myotubularmyopathy or MTM. It is a rare disease that affects the skeletal muscles.

"Patients are unable to walk. They're unable to speak, unable to swallow and unable to breathe without assistance. It's a childhood disease. It affects baby boys and it's universally fatal. So it's a bad, bad disease, said Childers.

Myotubularmyopathy affects dogs, too. In U.W. Medicine video, never seen by the public until now, gene-replacement therapy has resulted in a remarkable transformation in dogs and a possible cure for MTM.

The search for a cure began with the search for a dog by a Ponte Vedra Beach family. The son of Alison and Paul Frase was born with myotubularmyopathy. Joshua Frase was born on Feb. 2, 1995 with a devastating prognosis.

"My doctor came to me and she said, Alison, I really believe Joshua has a severe disorder and he's not gonna make it through the day.

Joshua continued to defy the odds, but only had the strength to move his right hand.

"Joshua cognitively was a normal little boy. He was just locked in a body," said Paul Frase.

At the time, Paul Frase was with the New York Jets. Within two weeks, his life would be thrown into even more turmoil. He was picked in NFL Expansion Draft.

"All of sudden Im the ninth pick of the Jacksonville Jaguars," Paul says.

His new team was more than 900-miles away.

"It was a decision that Allison and I made that I would continue to play football because we needed the benefits, the health care, we needed the money."

While his NFL career continued, the real battle was off the field, fighting the clock to try to find a cure. With 50 percent of children with MTM dying before their second birthday, Alison was determined to find a cure for her son Joshua. Alison was told by their geneticist at Boston Childrens Hospital that if she could find a dog with MTM, doctors could try gene-replacement therapy that could possibly lead to a treatment for her son.

"That's when her wheels started spinning and she said, we've got to figure something out," said Paul Frase.

Alison scoured the country looking for a dog with MTM and struck gold north of the border.

"We got a call back from a cowboy in the middle of Canada and he quickly said, I want to give you my dog. I want to help your son, said Alison.

The dog, named Nibs, delivered a litter of puppies and from there, a colony of dogs with the deadly form of muscular dystrophy was born.

Very rapidly over a few weeks, certainly by four months of age, the affected puppies are unable to walk. They're very, very weak and unfortunately, they require humane euthanasia, said Childers.

In an effort to save the lives of the dogs, and ultimately the lives of children, researchers at U.W. Medicine infused a replacement gene into puppies that have MTM.

In video obtained by Action News Jax, two puppies from the same litter showed a dramatic difference. One was given saline and the other was given a single treatment of gene replacement therapy. The puppy receiving the therapy quickly showed no signs of the disease.

Unbelievably fast. So, we see effects with two to three weeks, maximal within about six weeks. Weve now observed dogs for more than 4- years after infusion and they appear perfectly normal and healthy.

The two dogs have lived more than four years after receiving gene-replacement therapy. The dogs are remarkably active.

"These dogs would normally die around 2 months of age, 2 to 4 months of age. Because of the gene therapy, they've survived now to over four years," said researcher Dr. David Mack.

Doctors are cautious in their optimism but say its the most profound thing they have witnessed during their decades in medicine.

"I don't like to use the word miracle, but it's pretty darn close," said Childers.

Within months, clinical trials will begin around the world and children with the deadly disease will receive the same gene-replacement therapy as the dogs. Childers believes the chances are very, very good that the therapy will work in children. He is also painfully aware that the clock is ticking for children and their families praying for a miracle.

Joshua Frase lost his battle with MTM 41 days before his 16th birthday. His room remains the same with his glasses, cars and planes on bookshelves.

"It definitely brings back a lot of, just little poignant memories that put a smile on your face.

"He was a clown. He was a funny, intelligent, smart, normal kid. He was not just a son. He was a friend, said Paul Frase.

Frase played in the NFL and twice received the teams Courage Award. Frase said the courage came from his son.

"Joshua taught us about courage. He taught us about love. You learn a lot from these kids with these disabilities."

The grave marker for Joshua Frase includes a Bible verse, They shall run and not be weary, they shall walk and not faint.

It is a reminder of the debilitating disease that took his life. Childers said Joshuas legacy lives on through the dogs, doctors and his familys determination to find a cure.

"This is his legacy. No question about it. If it weren't for his parents, we wouldn't be having this conversation," said Childers. "If it weren't for just unrelenting, you know, just can do attitude, never take no for an answer, never quit on the part of his parents, yeah, this is absolutely his legacy. There's nothing that comes anywhere close to this. If this is the last thing I ever do in my research career, I'll die a happy man."

It is estimated that one in 50,000 children have myotubularmyopathy. Alison and Paul Frase started the Joshua Frase Foundation and believe there are, at least, 5,000 to 6,000 children with MTM.

Eighty percent of rare diseases are caused by a genetic defect. Doctors hope that gene-replacement therapy will, one day, lead to cures for other genetic diseases

2017 Cox Media Group.

Original post:
Former Jacksonville Jaguar, wife help discover medical breakthrough - ActionNewsJax.com

LAS VEGAS (KTNV) - Delays in diagnosis and patient care at the VA Southern Nevada are once again making headlines.

Contact 13 has a new report about multiple failures in the case of a local veteran.

Suffering from a condition where every day counts, the veteran had to wait six months for a proper evaluation.

The delay caused a domino effect in the diagnosis and treatment of the disease that ended his life.

In need of urgent surgery, the veteran fell victim to bureaucracy.

This newly released report from the VA Inspector General says the veteran also wasn't notified of test results in a timely fashion -- partly due to failed follow-up on a non-VA doctor's recommendation for a lung biopsy.

There were delays in getting authorization for non-VA medical care, difficulty getting chemotherapy medications and delayed treatment of what turned out to be lung cancer -- which kills more Americans than any other form.

It all happened in 2014 -- a scandal-plagued year for the VA when some 40 veterans in Phoenix died while on waiting lists for medical care.

Here in Las Vegas, Contact 13 exposed long wait times and canceled appointments compromising care for Southern Nevada veterans.

And that same year, we reported an eerily similar case to the one detailed in the OIG's report -- the story of Gene Broadwell, a Coast Guard veteran who died of lung cancer.

"This man who'd never been sick in his life was treated like some piece of garbage thrown out by the VA," said Broadwell's widow, Delores.

The last year of Gene Broadwell's life was peppered with appointment delays his wife believes were a death sentence.

"They could have found it maybe earlier and did the chemo and the radiation. He'd still be sitting here talking to us."

The VA acknowledged they could have done better to serve the man who served his country.

"Is it fair to say you don't want to see another Broadwell case?" Darcy Spears asked then-VA Chief of Medicine Dr. Milan Parekh

"Absolutely," Dr. Parekh answered. "I think that's a very fair statement."

But two years later, as the new report details, it happened again.

The VA says the deficiencies identified in the report have been resolved, partly due to nationally-mandated changes to the VA's Choice program, which allows veterans to receive care from non-VA doctors.

There are about 240,000 veterans living in the Las Vegas area.

VASNHS OFFICIAL RESPONSE

Since the 2014 timeframe in which this incident occurred, the Veterans Health Administration and VA Southern Nevada Healthcare System have implemented numerous changes and resolved all the deficiencies identified in the report to the OIGs satisfaction. Highlights include:

- Establishment of a better process for communicating test results to patients within 14 days (Current internal record reviews show 100 percent compliance).

- Implementation of the Veterans Choice Program nationwide in 2015 to streamline processes to provide authorizations for care in the community, track results and follow-up on outside provider recommendations (No reported significant delays in care that impacted outcomes of care).

- Processing more than 95 percent of STAT consults (a consult that clinical care is required within 24-48 hours) on time and processing a majority of all other consults within seven days.

- Improved education and procedures for sending patients seen in the Emergency Department to community facilities and intensive case management of their outside care.

- Realignment of Non VA Care and Choice program and expansion of staff to manage consults actions and decisions.

- Investigation and resolution of medication management issues and barriers. Currently, VASNHS completes 97.7 percent of non-formulary consults within 96 hours.

We are confident these actions along with expanded emergency care and access to same-day services at all primary care facilities for Veterans with urgent needs will prevent the recurrence of a similar issue in the future.

See original here:
Medical care delayed for Las Vegas valley veteran with deadly lung cancer - KTNV Las Vegas

May 23, 2017 Drs. Elisabeth D. Martinez, Dr. John Minna, and Dr. Maithili Dalvi. Credit: UT Southwestern

Patients with non-small cell lung cancer (NSCLC) often respond to standard chemotherapy, only to develop drug resistance later, and with fatal consequences. But what if doctors could identify those at greatest risk of relapse and provide a therapy to overcome or avoid it?

Researchers at UT Southwestern Medical Center believe they have an answer: a 35-gene signature that identifies tumor cells most likely to develop resistance to treatment. The study, published today in Cell Reports, points to a new pharmacologic approach to target chemo-resistant lung cancer and even prevent development of such resistance in the first place.

"Cancer relapse after chemotherapy poses a major obstacle to treating lung cancer, and resistance to chemotherapy is a big cause of that treatment failure," said study co-author Dr. John Minna, a Professor and Director of in the Hamon Center for Therapeutic Oncology Research at UT Southwestern. "These findings provide new insights into why resistance develops and how to overcome it."

Dr. Minna, with additional appointments in Pharmacology and Internal Medicine, also holds the Sarah M. and Charles E. Seay Distinguished Chair in Cancer Research and the Max L. Thomas Distinguished Chair in Molecular Pulmonary Oncology.

Investigators studied mouse and cellular models of NSCLC, a type of lung cancer that the American Cancer Society estimates accounts for 85 percent of all lung cancer cases in the United States.

"Previous studies have shown that up to 70 percent of those cancers develop resistance to standard therapy, such as the platinum-taxane two-drug combo that is often given," said study senior author Dr. Elisabeth D. Martinez, Assistant Professor of Pharmacology and in the Hamon Center. Both she and Dr. Minna are also members of UTSW's Harold C. Simmons Comprehensive Cancer Center.

Using long-term on/off drug cycles, lead author and former postdoctoral researcher Dr. Maithili Dalvi developed a series of cellular models of progressive tumor resistance to standard chemotherapy that ranged from very sensitive to highly insensitive. Next, the researchers identified genes commonly altered during the development of resistance across multiple cell line and mouse models and identified a 35-gene signature that indicated a higher genetic likelihood of chemotherapy resistance.

"It's like a fingerprint for resistance," Dr. Martinez said, adding that it was predictive in both cells and mouse models.

Next they compared this resistance biomarker using genetic profiles from human tumors in their National Cancer Institute (NCI) lung cancer Specialized Programs of Research Excellence (SPORE) database at UT MD Anderson Cancer Center in Houston. The database contained information on patient outcomes and those who had been treated with the two-drug chemotherapy. The genetic fingerprint for resistance correlated with cancer relapse in NSCLC patients in the database, she said.

Researchers discovered that as cancer cells developed greater resistance to chemotherapy, they progressively made higher amounts of enzymes called JumonjiC lysine demethylases. Dr. Martinez said these enzymes facilitate resistance by changing the expression of - or turning on and off - genes.

"Cancer cells use these enzymes to change, or reprogram, gene expression in order to survive the toxic stress of the chemotherapy. By changing the expression of genes, the tumor cells can adapt and survive the toxins," she said.

Investigators then tested two potential drugs, both JumonjiC inhibitors. One of them, JIB-04, was found by UT Southwestern researchers in the Martinez lab during a small-molecule screen conducted at the National Center for Advancing Translational Sciences' Chemical Genomics Center in Bethesda, Maryland.

"I believe this is the first report of NSCLC tumors taking advantage of multiple JumonjiC enzymes to reprogram gene expression in order to survive chemotoxic stress. In addition, and this is the most fascinating part: Dr. Dalvi found that greater chemotherapy resistance defines a new susceptibility to the JumonjiC inhibitors," she said. "The cancer cells develop a new Achilles' heel that we can hit."

Because the chemo-resistant cancer cells are dependent on JumonjiC enzymes for survival, inhibiting those enzymes returns cancer cells to mortality and vulnerability to cell death, she explained.

"We think these JumonjiC inhibitors have the potential to be used either to treat tumors once they become resistant to standard therapies, or to prevent resistance altogether," she said. "In our experiments these inhibitors appear to be much more potent in killing cancer cells than normal cells."

Later, researchers tested whether the Jumonji inhibitors JIB-04 or GSK-J4 prevented chemotherapy resistance. This strategy succeeded in cell cultures and partially prevented resistance in animal models, Dr. Martinez said.

Explore further: Team discovers opportunities to overcome cancer treatment resistance

A collaborative Cleveland Clinic, University of Oxford and Moffitt Cancer Center team of researchers has proven the theory that, while resistance to targeted treatment in cancer is truly a moving target, there are opportunities ...

Researchers from the transformation and metastasis group of the Bellvitge Biomedical Research Institute (IDIBELL), led by Dr. Eva Gonzlez-Surez, have recreated and characterized the development of resistance to chemotherapy ...

Working with human breast cancer cells and mice, researchers at Johns Hopkins say they have identified a biochemical pathway that triggers the regrowth of breast cancer stem cells after chemotherapy.

A new study by researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James) has identified a mechanism by which cancer cells ...

Mayo Clinic scientists have identified a specific protein implicated in drug resistance, as well as a possible therapeutic tool. Their work appears in the EMBO Journal.

A pioneering University of Liverpool research team have published a study that identifies the mechanism in the human body that causes resistance of pancreatic cancer cells to chemotherapy.

Scientists have found that carrying fat around your middle could be as good an indicator of cancer risk as body mass index (BMI), according to research published in the British Journal of Cancer today.

Patients with non-small cell lung cancer (NSCLC) often respond to standard chemotherapy, only to develop drug resistance later, and with fatal consequences. But what if doctors could identify those at greatest risk of relapse ...

Most women diagnosed with ovarian cancer undergo surgery to remove as many of the tumors as possible. However, it is usually impossible to eliminate all of the cancer cells because they have spread throughout the abdomen. ...

A study led by the University of Birmingham has made a breakthrough in the understanding of how different genetic mutations cause acute myeloid leukaemia.

Drinking just one glass of wine or other alcoholic drink a day increases breast cancer risk, finds a major new report by the American Institute for Cancer Research (AICR) and the World Cancer Research Fund (WCRF).

New research from the Keck School of Medicine of the University of Southern California (USC) shows new promise in the fight against one of the most lethal forms of cancer. Studies in mice with a mutation present in 90 percent ...

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Using a genetic signature to overcome chemotherapy-resistant lung cancer - Medical Xpress

A team of Canadian scientists has identified a gene that confers resistance to the broad-spectrum antibiotic fosfomycin, according to a study yesterday in Antimicrobial Agents and Chemotherapy.

The gene, dubbed fosA7, was found in 15 Salmonella enterica isolates from broiler chickens in British Columbia. The isolates were of the Salmonella Heidelberg serotype, which is commonly identified in poultry and has become one of the leading causes of salmonellosis in humans. In recent years, Heidelberg strains have become more resistant to antibiotics, limiting therapeutic options. The gene was also found in three other Salmonella serotypesAgona, Montevideo, and Tennessee.

Although polymerase chain reaction (PCR) testing showed that the gene was exclusively located on the chromosome of the Salmonella Heidelberg isolates, the concern is that fosA7 could potentially be spread to other strains of Salmonella and other families of bacteria if transferred to plasmidssmall, floating pieces of DNA that can be shared among bacteria through a process known as horizontal gene transfer.

"If it's on the chromosome, and it jumps to the plasmid, and the plasmid gets into another [type of bacteria], then the situation becomes worse," corresponding author Moussa Diarra, PhD, a research scientist with Agriculture and Agri-Food Canada, told CIDRAP News.

Increased use of fosfomycin in human and veterinary medicine would then increase the prevalence of the gene.

To see whether fosA7 could be transferrable, the scientists made a clone of the gene and copied it onto a plasmid inserted into a sample of the Salmonella serotype Enteritidis. Antibiotic susceptibility tests on the modified Enteritidis strains showed that a more than 256-fold increase in the minimum inhibitory concentration (MIC) of fosfomycin was needed to prevent growth of the bacteria.

"These results further suggest the fosA7 is responsible for fosfomycin resistance and if transferred on plasmids, it can induce a high level of resistance in the recipient bacterial strain," the authors write.

Fosfomycin is an older, well-tolerated antibiotic with activity against both gram-positive and gram-negative bacteria. It has been used to treat a variety of human infections, including urinary tract infections, and is considered a safe alternative for treating infections caused by multidrug-resistant bacteria, including those caused by Salmonella. The existence of a gene that could lead to the failure of fosfomycin would be highly problematic.

"It's an important antibiotic," Diarra said. "If we have resistance to it, too, then [treatment] becomes complicated."

As a result, Diarra and his colleagues call for "vigilant monitoring" for the spread of fosfomycin resistance in bacteria isolated from humans and animals.

Nontyphoidal Salmonella causes an estimated 1.2 million foodborne illnesses and about 450 deaths each year in the United States, according to the Centers for Disease Control and Prevention). The agency's most recent estimate of antibiotic-resistant Salmonella infections put the burden at 6,200 cases annually.

See also:

May 22 Antimicrob Agents Chemother study abstract

Read the original here:
New resistance gene found in Salmonella isolated from chickens - CIDRAP

by: Dave Wagner Updated: May 18, 2017 - 7:12 PM

SEATTLE - KIRO 7 has learned of a revolutionary treatment, here in Seattle, that has saved the lives of dogs and is just months away from being tested in children. In video obtained by KIRO 7, dogs that were destined to die show no signs of the disease after a single infusion of gene-replacement therapy. The disease is so deadly in children, 50-percent of them die before their second birthday.

"This is a huge deal. This is probably the most important thing we'll ever work on," said Dr. Casey Childers of U.W. Medicine.

For the past eight years, Childers has been focused on finding a cure for a form of muscular dystrophy called Myotubular Myopathy or MTM. It is a rare disease that affects the skeletal muscles.

"Patients are unable to walk. They're unable to speak, unable to swallow and unable to breathe without assistance. It's a childhood disease. It affects baby boys and it's universally fatal. So it's a bad, bad disease, said Childers.

Myotubular Myopathy affects dogs, too. In U.W. Medicine video, never seen by the public until now, gene-replacement therapy has resulted in a remarkable transformation in dogs and a possible cure for MTM.

>>Videos of children, dogs with Myotubular Myopathy

The search for a cure began with the search for a dog by a mother in Jacksonville, Florida. The son of Alison and Paul Frase was born with Myotubular Myopathy. Joshua Frase was born on February 2, 1995 with a devastating prognosis.

"My doctor came to me and she said, Alison, I really believe Joshua has a severe disorder and he's not gonna make it through the day.

Joshua continued to defy the odds, but only had the strength to move his right hand.

"Joshua cognitively was a normal little boy. He was just locked in a body," said Paul Frase.

With 50 percent of children with MTM dying before their second birthday, Alison was determined to find a cure for her son Joshua. Alison was told by their geneticist at Boston Childrens Hospital that if she could find a dog with MTM, doctors could try gene-replacement therapy that could possibly lead to a treatment for her son.

"That's when her wheels started spinning and she said, we've got to figure something out," said Paul Frase.

>> Website for families of children with Myotubular Myopathy: Joshua Frase Foundation

Alison scoured the country looking for a dog with MTM and struck gold north of the border.

"We got a call back from a cowboy in the middle of Canada and he quickly said, I want to give you my dog. I want to help your son, said Alison.

The dog, named Nibs, delivered a litter of puppies and from there, a colony of dogs with the deadly form of muscular dystrophy was born.

Very rapidly over a few weeks, certainly by four months of age, the affected puppies are unable to walk. They're very, very weak and unfortunately, they require humane euthanasia, said Childers.

In an effort to save the lives of the dogs, and ultimately the lives of children, researches at U.W. Medicine infused a replacement gene into puppies that have MTM.

In video obtained by KIRO 7 News, two puppies from the same litter showed a dramatic difference. One was given saline and the other was given a single treatment of gene replacement therapy. The puppy receiving the therapy quickly showed no signs of the disease.

Unbelievably fast. So, we see effects with two to three weeks, maximal within about six weeks. Weve now observed dogs for more than 4- years after infusion and they appear perfectly normal and healthy.

KIRO 7 was shown two dogs that have lived more than four-years after receiving gene-replacement therapy. The dogs are remarkably active.

"These dogs would normally die around two months of age, two to four months of age. Because of the gene therapy, they've survived now to over four years," said researcher Dr. David Mack.

Doctors are cautious in their optimism but say its the most profound thing they have witnessed during their decades in medicine.

"I don't like to use the word miracle, but it's pretty darn close," said Childers.

Within months, clinical trials will begin around the world and children with the deadly disease will receive the same gene-replacement therapy as the dogs. Childers believes the chances are very, very good that the therapy will work in children. He is also painfully aware that the clock is ticking for children and their families praying for a miracle.

At a home in Des Moines, Washington, you can hear a continuous hum of beeps and breathing machines. For the past nine years, Chris Bowers has defied the odds of living with MTM.

He really has been a rock star, said Virginia Bowers.

With a breathing tube, Chris speaks in sign language and moves quickly around his home in an electric wheelchair. He and his brothers, Ben and Sam, spend their free time playing with Legos. His parents hope the gene-replacement therapy might prolong and improve his life.

"Cautiously optimistic. It's hard to imagine because, Chris, this is what we know."

Joshua Frase lost his battle with MTM 41 days before his 16th birthday. His room remains the same with his glasses, cars and planes on bookshelves.

"It definitely brings back a lot of, just little poignant memories that put a smile on your face.

"He was a clown. He was a funny, intelligent, smart, normal kid. He was not just a son. He was a friend, said Paul Frase.

Frase played in the NFL and twice received the teams Courage Award. Frase said the courage came from his son.

"Joshua taught us about courage. He taught us about love. You learn a lot from these kids with these disabilities."

The grave marker for Joshua Frase includes a Bible verse, They shall run and not be weary, they shall walk and not faint.

It is a reminder of the debilitating disease that took his life. Childers said Joshuas legacy lives on through the dogs, doctors and his familys determination to find a cure.

"This is his legacy. No question about it. If it weren't for his parents, we wouldn't be having this conversation. If it weren't for just unrelenting, you know, just can do attitude, never take no for an answer, never quit on the part of his parents, yeah, this is absolutely his legacy. There's nothing that comes anywhere close to this. If this is the last thing I ever do in my research career, I'll die a happy man, said Childers.

It is estimated that one in 50,000 children have Myotubular Myopathy. Alison and Paul Frase started the Joshua Frase Foundation and believe there are, at least, 5,000 to 6,000 children with MTM.

Eighty-percent of rare diseases are caused by a genetic defect. Doctors hope that gene-replacement therapy will, one day, lead to cures for other genetic diseases.

2017 Cox Media Group.

Originally posted here:
Gene replacement therapy that works in dogs to be tested in children - KIRO Seattle

In Brief Researchers from Johns Hopkins Medicine in Maryland have discovered a rather unusual way to treat a severe form of age-related blindness. They found a virus inserted into the retina can be used to halt or even reverse the disease. A Unique Treatment

They say you dont fight fire with fire. However, researchers from Johns Hopkins Medicine in Maryland have found that sometimes a virus may be the best weapon against a disease.Their studyhas been publishedin The Lancet

The researchers werelooking for ways to treat a particular type ofage-related macular degeneration (AMD)known as a wet AMD. Its a rare and more severe form of the disease,affecting just 10 percent of all AMD patients, and it causes new blood vessels to grow under the retina, which then leak blood and fluid into the eye, leading to vision problems.

The researchers knewthey could halt and even reverse the condition by suppressing an overactive protein called vascular endothelial growth factor (VEGF). Other researchers had been able to do it with monthly eye injections, but this team was hoping to do it with just one injection.

The best way they found to do this was by using a common cold-like virus called AAV2 as a carrier of gene that activates the production of a differentprotein,sFLT01, tocounter VEGF.

In a preliminary trial involving 19 men and women 50 years old and above, the researchers injected the patients with a form of AAV2that was genetically engineered to penetrate retinal cells and deposit the gene. After the virus deposited the gene, the cells began secreting sFLT01 which bound to VEGF and prevented it from stimulating leakage and growth of abnormal blood vessels, explained a Johns Hopkins press release.

The clinical trial showed promising results, with the condition of four of the patients improving dramatically after just one viral injection. Two others saw some reduction in the fluid build up, and the treatment didnt produce any side effects in any patients. Even at the highest dose, the treatment was quite safe. We found there were almost no adverse reactions in our patients, said researcher Peter Campochiaro.

Of the patients that didnt respond, the researchers discovered that five naturally produced antibodies that would attack the AAV2 virus, rendering it unable to complete its gene depositing mission. They think these antibodies could be prevalent throughout the population, making it difficult to determine how effecting the treatment would actually be.

Nevertheless, this research is a step in the right direction, especially with AMD expected to affect almost 5.44 million people in the U.S. by 2050. This preliminary study is a small but promising step towards a new approach that will not only reduce doctor visits and the anxiety and discomfort associated with repeated injections in the eye, but may improve long-term outcomes, Campochiaro said.

View post:
An Experimental Gene Therapy Uses Viruses to Stop Age-Related Blindness - Futurism

Editors Note: Welcome to Eye Catching: Let's Chat, a blog series featuring contributions from members of the ophthalmic community. These blogs are an opportunity for ophthalmic bloggers to engage with readers with about a topic that is top of mind, whether it is practice management, experiences with patients, the industry, medicine in general, or healthcare reform. The series continues with this blog byJoshua Mali, MD, a board certified vitreoretinal surgeon at The Eye Associates, a private multi-specialty ophthalmology practice in Sarasota, FL. The views expressed in these blogs are those of their respective contributors and do not represent the views of Ophthalmology Times or UBM Medica.

Recently, I was watching a movie with my wife in which the plot revolved around the idea of futuristic medical technology and therapies including gene-targeted treatments. While most of it seemed far-fetched at best, there were some aspects that seemed not only feasible, but are actually being utilized in medicine today.

With this as the backdrop, I have been encouraged as a retinal specialist with all the excitement and promising new treatments in gene therapy. Given that there are several retinal diseases with known inherited patterns and confirmed genetic loci responsible for the clinical manifestations, our field is primed to benefit from the expansion of knowledge in this arena.

With the advent of genetic testing for inherited retinal diseases, this has provided another tool in our tool belt to help provide the most advanced care for our patients. The benefits of genetic testing include confirming clinical diagnosis to identify genetic disorders with systemic associations, provide information for family members, and potentially identifying patients that can benefit from gene targeted therapies.

A prime example of this is a new initiative called ID YOUR IRD, an inherited retinal disease (IRD) genetic testing program (Spark Therapeutics). According to the American Academy of Ophthalmology (AAO), genetic testing is appropriate for most patients with presumed genetically caused retinal degeneration and plays an important role in improving the accuracy of diagnosis and prognosis, providing patients and families with specific inheritance risks, and guiding treatment decisions.1

The ID YOUR IRD genetic testing panel includes 31 genes in which mutations have been found to cause certain early-onset, rod-mediated IRDs (see Figure 1). In particular, the three inherited retinal diseases that can be identified are retinitis pigmentosa (RP), choroideremia (CHM), and Leber congenital amaurosis (LCA). Adult and pediatric patients with signs and symptoms suggestive of certain early-onset, rod-mediated IRDs who are U.S. residents are eligible for the ID YOUR IRD initiative. The company has partnered with PreventionGenetics, a CLIA and ISO-accredited laboratory, to provide the genetic test at no cost to your patients.Courtesy of Joshua Mali, MD

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Genetic testing initiative for inherited retinal diseases shows great promise - ModernMedicine

By Robert F. ServiceMay. 17, 2017 , 2:30 PM

It takes more than a cast and a little time to heal many broken bones. Whether its a soldier wounded in battle, a car accident victim, or an elderly person who has fallen, bone damage can be so extensive that the bones never heal properly, leaving people crippled or with other severe problems. Now, researchers have combined ultrasound, stem cells, and gene therapy to stimulate robust bone repair. So far the work has only been performed in animals. But it has already been so successful that its expected to move quickly toward human clinical trials.

The new research has huge clinical significance, says David Kulber, who directs the Center for Plastic and Reconstructive Surgery at Cedars-Sinai Medical Center in Los Angeles, California, and who was not part of the study. The technology of being able to stimulate bone growth is really remarkable.

Its also one for which there is a glaring need. In the United States alone, some 100,000 people a year suffer from what is known as a nonunion fracture. In these cases, parts of a bone may be missing altogether or so badly splintered that the bone cant be reassembled. In such cases, doctors typically graft other bone into the site. Ideally this bone comes from the same personoften taken from the pelvis, a painful procedure that compounds a persons injuries and recovery time. When this isnt possible, physicians will turn to cadavers for the extra bone. But this bone must be sterilized before its implanted, robbing it of proteins and other signaling molecules that encourage its regrowth once transplanted, and lessening the chances of a full recovery.

Researchers have long tried to improve matters by growing new bone without use of a graft. To do so they typically first fill gaps in bone with a natural scaffolding material called collagen. This scaffolding encourages a persons own bone-forming stem cells, called mesenchymal stem cells (MSCs), to migrate into the area. The trouble is MSCs dont only differentiate into osteocytes, the bone-producing cells. They can also develop into either fat tissue cells or scar tissue.

Researchers have tried for years to steer MSCs into becoming osteocytes by exposing them to one or more bone morphogenetic proteins (BMPs), signaling molecules that trigger the cells to transform into bone-forming cells. But for this differentiation to occur, MSCs must be exposed to BMPs for up to a week. Yet if the BMPs are simply injected into the site of a fracture, they dissipate in just hours.

In an effort to produce a lasting BMP signal, researchers led by Dan Gazit, a regenerative medicine expert at Cedars-Sinai, as well as other groups, have previously turned to using viruses to introduce extra copies of BMP genes into MSCs so that the cells themselves will produce the proteins long enough to trigger their own differentiation. But success has been halting here, too.

Over the last several years, Gazits teamamong othershasdeveloped an alternative strategy for efficiently getting genes into MSCs without viruses. The researchers start by packing the wound with the usual collagen matrix and waiting for a couple of weeks for the stem cells to infiltrate the scaffold. They then create a solution containing numerous copies of their gene of interest alongside gas-filled micron-sized bubbles encased by a thin shell of fat molecules. After injecting this solution into the fracture site, they go over the area with an ultrasound wand, much as its done by obstetricians to check on the health of a fetus. The wands ultrasound pulses burst the microbubbles, briefly punching nano-sized holes in any adjacent stem cells, which allows the genes in the solution to enter.

In 2014, Gazit and his colleagues reported that they used this procedure to introduce nontherapeutic reporter genes into large fractures in animal models. But when they used the procedure to introduce genes for two different BMPsBMP-2 and BMP-7they detected some bone regrowth in the animals, but not enough to heal the fractures.

Gazits group has gotten better results by using the same approach to insert copies of the gene for BMP-6 into pigs that had been surgically given 1-centimeter gaps in a leg bone. After waiting 8 weeks, they found that the bone gap was closed and the leg fracture was healed in all of the treated animals. In fact, the procedure was so effective that the fractures healed as well as when bone grafts were carried out using bone from the same animal, the currently preferred treatment, they report today in Science Translational Medicine.

The results are just the type of thing we need to move this field forward, says Johnny Huard, an orthopedics researcher at the University of Texas Health Science Center in Houston. However, he notes, the pigs used in this study were all under 1 year in age. Younger animals, including people, tend to have far more MSCs than older ones, he says, yet large fractures are far more common in the elderly than the young. So Huard suggests that before the approach is ready for testing in people with bone fractures, it would be good to first see whether its equally successful in older animals.

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Tiny bubbles and a bit of gene therapy heal major bone fractures in pigs - Science Magazine