2021 Grant Recipients

UW Medicine - Institute for Stem Cell and Regenerative Medicine

Seattle, WA

Researcher: David L. Mack, Ph.D.

​Research Program: Neuromuscular Disease Research Fund in the Department of Rehabilitation Medicine

Specific Need: Program Funding

Grant Amount: $50,000

 

2019 Grant Recipients

Medical College of Wisconsin

Milwaukee, WI

Researcher: Michael W. Lawlor, MD., Ph.D.

Specific Need: Congenital Muscle Disease - Tissue Repository

Grant Amount: $8,000

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2017 Grant Recipients

UW Medicine - Institute for Stem Cell and Regenerative Medicine

Seattle, WA

Researchers: Martin K. Childers, D.O., Ph.D., and David L. Mack, Ph.D.​

Research Program: XLMTM Patient-Specific iPS Skeletal Muscle Stem Cells Research Fund

Specific Need: Program Funding

Grant Amount: $6,500

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The Hospital for Sick Children Foundation

Toronto, Ontario, Canada

Researcher: James Dowling, M.D., Ph.D

Specific Need: MTM Clinical Trial Funding

Grant Amount: $30,000

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2016 Grant Recipients

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The Hospital for Sick Children Foundation

Toronto, Ontario, Canada

Researcher: James Dowling, M.D., Ph.D

Specific Need: MTM Clinical Trial Funding

Grant Amount: $40,000

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UW Medicine - Institute for Stem Cell and Regenerative Medicine
Seattle, WA
Researchers: Martin K. Childers, D.O., Ph.D., and David L. Mack, Ph.D.
​Research Program: See Synopsis Below:
Specific Need: Program Funding
Grant Amount: $10,000

 

Project: Understanding gene expression dysregulation downstream of MTM1 deficiency in canine skeletal muscle and investigating molecular correction after rAAV2i8-hMTM1 gene therapy.

The goal of this project is to use a powerful technique called RNA Sequencing to investigate changes in gene expression in skeletal muscle due to the deficiency of MTM1 protein.  This approach will reveal molecular defects directly caused by an absence of MTM1 protein, but also give us the ability to track the pathology at the molecular level.  By comparing the genes expressed in muscle biopsy samples from normal, affected and affected/treated dogs we can, for the first time identify the molecular changes that underlie the correction of the pathology observed in previously reported studies.

 

2015 Grant Recipients

 

Boston Children's Hospital

Boston, MA
Researcher: Alan Beggs, Ph.D.
​Research Program: Beggs Laboratory Congenital Myopathy Research Fund
Specific Need: Laboratory Funding
Grant Amount: $10,000

 

MTM-CNM Family Connection, Inc.

Specific Need: 2015 MTM-CNM Family Conference 

Amount: $1,000

 

Cure CMD

Specific Need: Congenital Muscle Disease International Registry (CMDIR) Research Programs (listed below)

Amount: $2,825

 

Prospective Event Rate Study In Males With X-Linked Myotubular Myopathy
Researcher: Sabine de Chastonay, PhD, CMDIR
This study will look at health complications connected XLMTM, in this study called an EVENT, such as emergency room visits/hospitalizations, a reaction to a medication or a complication from a medical procedure. This information will help doctors take care of children and adults with MTM and help researchers prepare for future clinical trials. This study is co-led by the CMDIR and the University of Michigan.

 

MTM1 Carrier Survey
Researcher: Sabine de Chastonay, PhD, CMDIR 
The Beggs Lab invites any mother who has a son diagnosed with X-linked myotubular myopathy (XLMTM) to complete a questionnaire about their medical history and current abilities. When a boy has inherited a genetic change in the MTM1 gene, he is affected with X-linked myotubular myopathy.  MTM1 carriers, women who are not MTM1 carriers but have a son with XLMTM, and mothers who do not know their carrier status are all welcome to participate. We hope to learn more about what symptoms, if any, mothers of children with XLMTM may have to be better able to characterize the impact of MTM1 mutations on the body. This study is in collaboration with Beggs Lab and the NIH.

 

Medical College of Wisconsin

Milwaukee, WI

Researcher: Michael W. Lawlor, MD., Ph.D.

Specific Need: Congenital Muscle Disease - Tissue Repository

Grant Amount: $8,000

 

Boston Children's Hospital

Boston, MA
Researcher: Alan Beggs, Ph.D.
​Research Program: Beggs Laboratory Congenital Myopathy Research Fund
Specific Need: Laboratory Funding
Grant Amount: $5,000

 

 

2014 Grant Recipients

 

Will-Cure is proud to announce an award of $40,000.00 to three extremely important MTM projects. This donation is a direct result of our successful 2014 fundraising.

 

These three projects are crucial for our community. Our sizable donation comes at a time when projects were not fully funded. Absent this donation, the results of this research would been postponed for years.  Will-Cure is excited to eliminate funding concerns and shorten the time frame for results.

 

The first project will examine gene therapy effects in animals with advanced, late statge disease.  This project is crucial for the older MTM children in the MTM community.  The second project examines the effects of a second injection of gene therapy treatment in order to determine potential immune responses. The third project will examine gene therapy effects on human cells.

 

UW Medicine - Institute for Stem Cell and Regenerative Medicine
Seattle, WA
Researchers: Martin K. Childers, D.O., Ph.D., and David L. Mack, Ph.D.
​Research Program: See Synopsis Below:
Specific Need: Program Funding
Grant Amount: $40,000

 

Administration of MTM Gene Therapy to Dogs with Advanced Myotubular Myopathy:

Babies born with a disease called X-linked myotubular myopathy (XLMTM) have severe muscle weakness and many die prematurely from failure of the muscles used for normal breathing. Some patients survive to older age, but do not live long because of severe weakness of the breathing muscles. There is no known cure or effective treatment for this disease. We have found a way to replace the defective gene that causes XLMTM. This new method of gene replacement has been tested in mice (designed in the laboratory to have the same disease as patients) and more recently tested in dogs (that are born with a naturally occurring disease just like XLMTM patients). We found that if we treat young or even old mice with the disease, they completely recover. We have not yet tested this idea in dogs with severe late-stage disease. In this research program, we will extensively test the safety and effectiveness of gene replacement in dogs with late stage disease caused by XLMTM. Dogs allow for repeated measures of safety and effectiveness and they are closer in size and function to humans compared to tiny mice.

 

Immunological Effects of Administering a Second Dose of AAV8-MTM1 to Dogs with Myotubular Myopathy:

X-linked myotubular myopathy (XLMTM), a devastating congenital muscle disorder with no effective therapy.  Average life expectancy is only 29 months and 80 percent of patients who survive beyond two years require ventilator support. The most immediate hope to treat XLMTM is gene replacement therapy. Our recent data (Childers et al, Sci Tran Med, 2014) established that a single systemic treatment with AAV8-MTM1 resulted in long-term (at least one year) survival and essentially complete amelioration of symptoms in both mice and dogs with MTM1-deficient muscles. While systemic disease progression was halted after AAV8-MTM1 infusion, and to some extent reversed in young MTM1-deficient dogs, AAV does not integrate into the genome. Therefore, subsequent AAV-MTM1 treatment will inevitably be required to sustain therapeutic level of MTM1 in patients when initial treatment is at a very young age, due to significant increase in muscle mass as the boys get older.  A pilot study in MTM dogs is currently underway to test whether a second dose of AAV8-MTM1 will elicit an immune response and possibly neutralize any future therapeutic benefit.

 

Disease-in-a-Dish Model for XL-MTM skeletal muscle using patient-specific iPS cells:

The goals of this project are to develop an in vitro model system for X-linked myotubular myopathy for the purpose of identifying new compounds that can augment or enhance the AAV8-MTM1 gene therapy.  Although unexpected, given the strong data coming out of the canine model, it remains possible that complete reversal of the disease will not be achieved in all patients.  More importantly, the long-term effects of gene therapy in the dogs are just now becoming clear.  MTM1-affected dogs treated with a normal copy of the gene show impressive muscle regeneration after more than one year, but boys with myotubular myopathy need a treatment that lasts throughout their lives.  Therefore, our objective is to generate a research tool that will allow us to study human MTM1-deficient skeletal muscle in culture, and then use that platform to discover new drugs that can correct the defect in the dish.  Compounds identified using this personalized medicine approach have a higher likelihood of working in the patient because the patient’s own cells were used to find the drug.  An added benefit will be that we can address questions from the FDA more quickly and insightfully once we have this human system operational in the lab.  A future, loftier outcome from this project could be the construction of MTM1-deficient neuromuscular junctions.  In collaboration with other ISCRM investigators, methods are being developed to produce not only skeletal muscle precursors but also motor neurons, with the intention of combining them in culture to better understand the excitation-contraction coupling defect in this disease.

 

UW Medicine - Institute for Stem Cell and Regenerative Medicine
Seattle, WA
Researchers: Martin K. Childers, D.O., Ph.D., and David L. Mack, Ph.D.
​Research Program: Variable Rescue - Gene Therapy for Myotubular Myopathy
Specific Need: Program Funding
Grant Amount: $15,000

 

Synopsis:

 

Babies born with a disease called X-linked myotubular myopathy (XLMTM) have severe muscle weakness, and many die prematurely from failure of the muscles used for normal breathing. Some patients survive longer, but do not live long because of severe weakness of the breathing muscles. There is no known cure or effective treatment for this disease. We have found a way to replace the defective gene that causes XLMTM. This new method of gene replacement has been tested in mice (designed in the laboratory to have the same disease as patients) and more recently tested in dogs (that are born with a naturally occurring disease just like XLMTM patients). The new project will add variable conditions to determine of any of the variables have any impact on the previous results.