A Boy With the Will to Live: Biobanking Contributing to Breakthroughs in Rare Diseases

February 28th, 2018 in Biobanking Breakthroughs

Joshua Frase was born on February 2, 1995. When Joshua was three months old, a muscle biopsy revealed that he had the ultra-rare X-linked myotubular myopathy (XLMTM), a muscle disorder. Tragically, only 50% of the children born with Joshua’s disorder live to the age of two. Fewer still survive past their early school years. Joshua’s parents, Paul and Alison, were told that he may not survive the day. After 24 days in the NICU, his parents were told to take their child home and enjoy the remainder of the little time they had left. Joshua lived to 40 days shy of his 16th birthday.

X-Linked Myotubular Myopathy

Children born with X-linked myotubular myopathy, which affects about 1 in 50,000 male births, have very weak skeletal muscles, causing them to appear floppy (learn more here). They also have severe respiratory difficulties, gait problems and feeding challenges along with poor muscle development. Survival beyond birth requires intensive support, often including tube feeding and mechanical ventilation, but effective therapy is not available for patients, and most die in childhood.

Joshua Frase Foundation

Joshua’s parents, Paul and Alison established the Joshua Frase Foundation (JFF; learn more here) in 1995. They embarked on a journey to understand the pathology of this disorder by building a trans-Atlantic team of world-renowned researchers. Leading research partners were the Boston Children’s Hospital, the Wake Forest Institute of Regenerative Medicine, the Medical College of Wisconsin and the University of Washington. Through the sharing of samples and data the research was focused on:

  •  Understanding the pathology of the disease
  •  Possible regenerative medicine applications and
  •  Gene Replacement Therapy (as early as October 2000)

One of the many biobanks that contributed to the research on this rare condition was the Congenital Muscle Disease Tissue Repository (CMD-TR), an IRB-approved biorepository at the Medical College of Wisconsin within the Lawlor Lab. Research has supported many discoveries: an amazing outcome facilitated by sharing and collaboration. You can learn more about the research leading to the development of new therapies for MTM in this video.

Fast track 22 years of hard work, commitment, perseverance and scientific collaboration around the world brought a monumental accomplishment: Audentes Therapeutics announced that the first MTM child was provided with gene replacement therapy in September 2017. This was a significant milestone accomplished in the field of neuromuscular research, and for all children and families affected with XLMTM.

“It has been an honor and a privilege to advocate for the last 22 years alongside these children and families, from diagnosis of this rare disorder to the recent commencement of clinical trials,” said Alison Rockett-Frase Joshua’s mother and Founder and President of the Joshua Frase Foundation. “Sharing our story continues to fuel the fire of hope that one day soon there will be a cure—not just for MTM, but for many rare genetic disorders. We live in exciting times for research initiatives.” The JFF endeavor to unlock the mysteries of MTM has culminated in their ability to give guarded hope to families across the world that their child might have hope for a brighter future.

Article written by Kozlakidis Z; information provided by Rubinstein Y and the ISBER Rare Diseases Working Group; edited by Seiler C.; All the material, images and information contained in this communication have been provided with the kind and expressed permission of the JFF. If you are interested in joining the ISBER Rare Diseases Working, please contact us by email at info@isber.org.


Background on MTM:

Centronuclear myopathy (CNM) is the umbrella term under which are several forms of myopathy including: XLMTM, Autosomal Dominant CNM, Autosomal Recessive CNM, and Autosomal Dominant. All of these these are rare genetic disorders that affect skeletal muscle tissue. The severity of the disease differs from case to case, ranging from slightly debilitating to fatal. Most often, CNM/MTM will be present at birth, however, symptoms can manifest at any stage in life. A child born with either of these conditions will most likely show signs of “hypotonia” (low muscle tone). Most of the time, these babies will also struggle with the ability to suck, swallow, and breathe spontaneously on their own.  As children get older and their bodies get larger, they may find that they have a harder time moving around over time.  Some people with Dynamin-2 mutations (DNM2) CNM may find that their weakness progresses slowly over many years.

More about the Joshua Frase Foundation

At the time of Joshua’s diagnosis, there was no known cure for MTM. Faced with a grim prognosis, Joshua’s family started a long journey and mission of finding a cure for this rare disorder. In the fall of 1996, Paul Frase and his former Syracuse and New York Jets teammate, Pat Kelly, decided it was time for the Joshua Frase Foundation to begin raising funds. A committee was formed that year and a development professional was hired. The group worked together to gather old college friends, former teammates and a team of corporate supporters to raise not only money, but also awareness of myotubular myopathy and other devastating neuromuscular diseases. The JFF Muscle Dream Team Gala quickly became one of the premier events of its kind. The JFF Gala has raised nearly $7 million to help world-renowned researchers at Boston Children’s Hospital, Harvard Medical School, Wake Forest Institute for Regenerative Medicine, Toronto SickKids, The Medical College of Wisconsin, and University of Florida uncover potential treatments for neuromuscular disorders. JFF’s work fosters hope for more than 2,000 children who are diagnosed with neuromuscular disorders each year. JFF’s team remains committed to fighting for the Joshua’s of the world.

One of the treatments currently on trial is using an engineered adenovirus vector. The vector carries a replacement of the MTM1 gene has been used in two animal models: mice and dogs. Both animals responded to a single intravascular injection of an adenovirus vector engineered for gene transfer therapy.  Eager to expedite the next round of research that could potentially save her son, Joshua’s mother, Alison Rockett-Frase, found Nibs, who was a female laborador retriever and  carrier of MTM. The inspirational short film, “Brick in the Wall” (Can be viewed online here) offers a unique perspective of how compassionate, dedicated animal care experts can not only change the trajectory of disease research—and the lives of patients and their families—but also serve as the guardian and friend of these lab animal heroes.


  • Joshua Frase Foundation Website
  • Press Kit
  • The announcement of data from Audentes Therapeutics using our technology in gene transfer therapy here

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