Research
Joshua Frase Foundation - Research has supported many discoveries
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 Boston Children’s Hospital 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.
- 2005 - 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.
- 2006 - JFF and Wake Forest University: Recap Last 10 Years at the Wake Forest Institute for Regenerative Medicine (Director: Anthony Atala)
- 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 - Major Breakthrough: The Miracle of Nibs
- 2010 - Nib's Legacy Lives On
- 2011 – Publication of first pre-clinical trial of Myostatin inhibition to increase muscle size in mice with XLMTM.
- 2011 – Discovery of new functions for myotubularin, including control of muscle skeleton and energy production by mitochondria.
- 2012 – Announced creation of the “Mtm1 R69C” mouse, a new milder model of XLMTM.
- 2012 – NIH funds a collaborative grant to study the dog model of XLMTM.
- 2012 – Demonstration of abnormal neuromuscular transmission in XLMTM and first preclinical trial of a drug to enhance transmission in mice with XLMTM.
- 2012 – Publication of a “Clinical Utility Gene Card” to establish diagnostic standards for XLMTM and centronuclear myopathy.
- 2012 – Reported establishment of the first colony of dogs with XLMTM and determination of their natural history and disease progression.
- 2012 – First report of defective growth and survival of XLMTM cells.
- 2012 – Comprehensive review and publication of the largest series of DNM2-related centronuclear myopathy to date.
- 2012 - Muscle function in a canine model of X-linked myotubular myopathy.
- 2012 - MTM1 mutation associated with X-linked myotubular myopathy in Labrador Retrievers
- 2013 – NIH renews funding for centronuclear myopathy research at Boston Children’s Hospital.
- 2013 – Report of a new type of mutation - duplications in the MTM1 gene and establishment of a clinical test at the University of Chicago Genetic Services Laboratory.
- 2013 – Studies on the interactions between myotubularin and its partner MTMR12 in zebrafish, and in mouse and human cells.
- 2013 – First report of a successful preclinical therapeutic trial of protein replacement therapy for XLMTM.
- 2013 – Discovery of a new gene, titin, as a cause of centronuclear myopathy.
- 2014 - Press Release; Gene Therapy Rescues myotubular myopathy
- 2014 - Boston Children's Hospital's science and clinical innovation blog: Gene therapy strengthens weak muscles in congenital myopathy
- 2014 - Created International Family Registry for Centronuclear and Myotubular Myopathies
- 2014 - Preclinical Success in Two X-Linked Pediatric Diseases Sets Stage for Clinical Trials
- 2014 - Gait characteristics in a canine model of X-linked myotubular myopathy
- 2014 - Gene therapy prolongs survival and restores function in murine and canine models of myotubular myopathy.
- 2014 - Respiratory assessment in centronuclear myopathies.
- 2014 - Ultrasound assessment of the diaphragm: Preliminary study of a canine model of X-linked myotubular myopathy.
- 2014 - Syngeneic myoblast transplantation improves muscle function in a murine model of X-linked myotubular myopathy.
- 2014 - Regenerative rehabilitation: a new future?
- 2014 - Discovery of new gene, SPEG, as a cause of centronuclear myopathy.
- 2014 - Gene therapy for inherited muscle diseases: where genetics meets rehabilitation medicine.
- 2015 - X-Linked MTM found in Australian Rottweilers
- 2015 - Guiding intramuscular diaphragm injections using real time ultrasound and electromyography.
- 2015 - Neurological Scoring System for canine X-linked myotubular myopathy.
- 2015 - Comprehensive assessment of disease progression in canine X-linked myotubular myopathy.
- 2016 - Skeletal Muscle Pathology in X-Linked Myotubular Myopathy: Review With Cross-Species Comparisons
- 2017 - Mediated Gene Therapy Drives Whole-Body Correction of Myotubular Myopathy in Dogs
- 2017 - Gene Therapy Leads to Long-Term Benefits in Dog Model of Devastating Childhood Disease
- 2017 - Long term follow-up of MTM1 gene therapy shows benefits lasting for at least 4 years.
- 2017 - Audentes Therapeutics Announces FDA Clearance of Investigational New Drug Application for AT132 to Treat X-Linked Myotubular Myopathy
- 2017 - Audentes Therapeutics Reports Dosing of First Patient in ASPIRO, the Phase 1/2 Clinical Trial of AT132
- 2017 -A Multicenter, Retrospective Medical Record Review of X-Linked Myotubular Myopathy: The RECENSUS Study
- 2018 - Audentes Announces Continuing Positive Data from First Dose Cohort of ASPIRO, a Phase 1/2 Clinical Trial of AT132 in Patients With X-Linked Myotubular Myopathy
- 2018 - Audentes Announces Positive Interim Data from First Dose Cohort of ASPIRO, a Phase 1/2 Clinical Trial of AT132 in Patients With X-Linked Myotubular Myopathy
- 2018 - Audentes Therapeutics Reports Second Quarter 2018 Financial Results and Provides Update on ASPIRO, the Phase 1/2 Clinical Trial of AT132 in Patients with X-Linked Myotubular Myopathy
- 2018 - Audentes Announces Regenerative Medicine Advanced Therapy (RMAT) Designation Granted by the FDA to AT132 for the Treatment of X-Linked Myotubular Myopathy
- 2018 - Audentes Therapeutics Presents New Positive Interim Data from ASPIRO, the Phase 1/2 Clinical Trial of AT132 in Patients with X-linked Myotubular Myopathy, at 23rd International Annual Congress of the World Muscle Society
- 2019 -Mortality and respiratory support in X-linked myotubular myopathy: a RECENSUS retrospective analysis
- 2019-Audentes Therapeutics (BOLD) Presents At 24th International Annual Congress of the World Muscle Society - Slideshowpen
- 2020 - JAMIA Open -Alison Rockett Frase published in The case for open science: rare diseases
FUTURE GOALS
- Expansion of the XLMTM dog colony for use in preclinical development of gene and other therapies.
- Develop gene therapy for XLMTM.
- Develop protein replacement therapy for XLMTM.
- Partner with biotechnology companies and the patient community to develop the “natural history” data that the FDA will require for clinical trials of new therapies.
- Develop zebrafish models of other centronuclear myopathies.
- Screen drug libraries for new therapies using zebrafish with centronuclear myopathy.