Accomplishments

JFF and Children’s Hospital Boston: Over ten years of Partnership and Progress

With the help of all Joshua’s friends and benefactors, JFF has supported many discoveries that have been published and disseminated to the greater medical and scientific community.  Highlights of this JFF-sponsored research in Genetics at Children’s Hospital Boston and Wake Forest include:

PAST ACCOMPLISHMENTS

• 1996 - Creation of the Joshua Frase Foundation and the start of funding of research on X-linked myotubular myopathy (XLMTM) and related neuromuscular disease.
• 2001 - NIH funding of the Program Project at Children’s Hospital Boston, supporting research on XLMTM and related neuromuscular diseases.
• 1999 – 2004 - Discovery and analysis of several new muscle genes and investigation of their relationship to congenital myopathies.
• Analysis of muscle defects in X-linked myotubular and centronuclear myopathies.
• 2002 – 2003 - Analysis of gene expression patterns in normal and diseased muscles to understand how the effects of weakness might be reversed.
• 2004 - Development of a cell-based model of normal muscle development used to study the effects of myotubularin loss in XLMTM.
• 2005 - Discovery of DNM2, a new gene for centronuclear myopathy.
• Identification and characterization of muscle stem cells, which are a potential therapy option for muscle disease.
• 2005 - Establishment of the first colony of “MTM mice” in the United States to test new treatments for congenital myopathy.
• 2007 - Discovery that boys with XLMTM who have larger muscle fibers survive longer.
• 2008 – Proved that gene therapy is an effective treatment for XLMTM in mice.
• 2009 – Discovered that weakness in XLMTM is caused by abnormal calcium flow in muscle.
• 2010 – Identification of the first large animal model for XLMTM, the Labrador retriever.
• 2010 - Establishment of a colony of XLMTM dogs to better understand the disease and develop treatments.
• 2010 – Completion of first pre-clinical trial of Myostatin inhibition to increase muscle size in mice with XLMTM.

FUTURE GOALS

• Development of a new mouse model for a less severe form of XLMTM to further increase our understanding of the disease and test potential therapies.
• Completion of the second pre-clinical trial of myostatin inhibition in the mice with less severe XLMTM.
• Understanding the natural history and progression of XLMTM in the dog model.
• Further clarifying the role of myotubularin (the protein that is not working in boys with XLMTM) and related proteins in the muscle to learn why its absence makes muscles weak.
• Identifying and understanding other genes associated with the congenital myopathies, which could improve our understanding of XLMTM.
• Establishment of a strategic alliance with Genethon to provide gene therapy vectors for pre-clinical trials in the XLMTM dog model.
• Investigating additional therapies in the mouse and dog models of XLMTM.