Gene replacement therapy that works in dogs to be tested in children

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.

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 Children’s 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.  We’ve now observed dogs for more than 4-½ 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 it’s 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 team’s 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 Joshua’s legacy lives on through the dogs, doctors and his family’s 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.