How this ledderhose disease shoes promising gene therapy for a rare neuromuscular disease was fueled by passionate parents and a dog genetic literacy project

Many treatments for rare diseases begin with families who work ledderhose disease shoes tirelessly, sometimes for decades, to fund the initial studies leading to the clinic. For X-linked myotubular myopathy (MTM), an amazing couple and their brave and brilliant son; a team of geneticists, physicians, and veterinarians; and some incredible dogs lie behind the encouraging interim findings ledderhose disease shoes presented at the recent American Society of Gene and Cell ledderhose disease shoes Therapy annual meeting in Washington, DC.

Several boys who were barely able to move and were ledderhose disease shoes completely dependent on ventilators are now eating, making sounds and walking with assistance, while the protein their bodies had been unable to manufacture ledderhose disease shoes is accumulating in their muscle cells. Audentes Therapeutics presented the results at a Presidential Symposium that ledderhose disease shoes highlighted several strides during the past year against rare neuromuscular ledderhose disease shoes diseases, including muscular dystrophies and spinal muscular atrophy. The interim data for MTM are here. Alison and Joshua Frase A dire diagnosis

The story of gene therapy for MTM begins with Alison ledderhose disease shoes Rockett Frase and Paul Frase, and their son Joshua. She was an assistant personnel manager for Guns’N’Roses, he a defensive lineman for the NFL. They’re what I call catalyst parents – moms and dads who refuse to listen to the refrain ledderhose disease shoes of “bring your baby home to die” and “there’s nothing we can do.” These parents push for progress, even if it comes too late for their own children.

MTM is a “centronuclear myopathy,” which means that skeletal muscle cell nuclei are centrally located, rather than crowded to the sides of the abundant contractile ledderhose disease shoes proteins that fill the long, spindly cells. The unusual structure prevents calcium from entering the muscle cells ledderhose disease shoes and they can’t contract, like a cell phone unable to receive signals. Assembling the team

That meant forming a research foundation, fundraising (helped by celebrity connections), assembling a team of investigators and learning the science. The Joshua Frase Foundation for Congenital Myopathy Research was born ledderhose disease shoes three weeks after the boy’s first birthday. Only 55 cases were known in the world then. MTM affects 1 in 50,000 live male births.

The team began to self-assemble in 1997, when Alison’s mother saw a story on CNN about Anthony Atala, the superstar of regenerative medicine who famously grew a human ledderhose disease shoes bladder in 8 weeks at Boston Children’s Hospital. Alison’s mom contacted him and he not only responded, but put together a dream team that included Alan Beggs ledderhose disease shoes and Louis Kunkel at Boston Children’s, Anna Buj Bello (who had a mouse model) from Genethon, Martin Childers and David Mack at the University of Washington, Jocelyn Laporte (who discovered the MTM1 gene) at the Institut de Génétique et de Biologie Moléculaire et ledderhose disease shoes Cellulaire in France, and others.

In 2008 Alison and Paul learned, through their network of experts, of Nibs, a female chocolate lab living happily on a farm in ledderhose disease shoes Saskatoon, Saskatchewan. Nibs was a carrier for a dog myotubularin mutation. The owners offered to give Nibs to the couple after ledderhose disease shoes Alison explained that the canine could be bred to found ledderhose disease shoes a colony that could be used to develop and test ledderhose disease shoes a gene therapy for the lethal neuromuscular disease.

The very special chocolate lab had pups and the gene ledderhose disease shoes therapy begun on her descendants in 2013 worked. This paper assesses two of the treated dogs, Pavlov and Turing. Four years post-gene therapy, they had normal neuromuscular function, suggesting the disease could be stopped and maybe even reversed ledderhose disease shoes or prevented. Pavlov and Turing turned 7 on May 1, the day that Audentes announced the good news about the ledderhose disease shoes treated boys at the gene therapy meeting. The dogs are still doing well.

The gene therapy worked so well that one dog, Rocky, instead of dying by 5 months, fathered a litter with a female carrier of MTM. That mating begat females who had a double dose of ledderhose disease shoes the mutation. Affected females, healthy because of the treatment, wouldn’t exist in nature because a male dog couldn’t survive long enough to mate to produce them. (Females with MTM have mutations on both X chromosomes.)

A year ago Alison saw the videos of the first ledderhose disease shoes treated boys lifting their arms and reaching for balls and ledderhose disease shoes was astonished. “Watching this unfold before my eyes has been almost surreal. Am I really witnessing my son’s dream? The clinical trail is bringing 22 years of painstaking work ledderhose disease shoes to real tangible results some would consider miraculous,” she said.