Clinical Studies and Trials

For information about why participating in clinical studies is important to the development of therapies for dysferlinopathy please read the following: Letter from Jain Foundation’s President, Plavi Mittal

Clinical Studies

Studies recruiting LGMD2B/Miyoshi patients:

• International Clinical Outcome Study for Dysferlinopathy - Patient recruitment starts June 2012
  This study is being sponsored by the Jain Foundation. The goal of the study is to define the natural progression of dysferlinopathy (LGMD2B/Miyoshi) in a large group of genetically confirmed patients and study a selection of possible outcome measures for use in future treatment trials. Please note: Genetic confirmation of your diagnosis is required for participation.

  The results of this study will provide us with a better understanding of the clinical aspects of dysferlinopathy and identify the best outcome measures to test the efficacy of potential therapies in future clinical trials.

• Evaluation of Limb-Girdle Muscular Dystrophy
  http://www.clinicaltrials.gov/ct2/show/NCT00893334
  This study is recruiting the following types of patients: LGMD2B/Miyoshi, LGMD2A, LGMD2I, and BMD. The purpose of this study is to understand the biochemistry of different types of Limb-Girdle Muscular Dystrophy (LGMD) and to determine appropriate outcome measures for future clinical treatment trials for LGMD. It consists of a one day clinical evaluation that involves strength and muscle functional testing, various other clinical tests, and two blood draws. Please note: Genetic confirmation of your diagnosis is required for participation.

  The results of this study could increase our understanding what is going on molecularly in LGMD2B/Miyoshi and identify possible outcome measures that could be used in future clinical trials.

Studies recruiting other types of muscular dystrophy patients that could provide helpful information for LGMD2B/Miyoshi:

• Safety Study of Transvenous Limb Perfusion in Human Muscular Dystrophy
  http://www.clinicaltrials.gov/ct2/show/NCT00873782

  This study is currently recruiting various types of muscular dystrophy patients which include LGMD2B/Miyoshi patients. The goal of the study is to test the safety and feasibility of limb perfusion as a delivery method for gene therapy.

  The genetic basis of many types of muscular dystrophies is well defined, which makes gene therapy a potential treatment option in the future. A key step to the development of gene therapy as a viable treatment option involves the identification of a safe and effective way of delivering the genetic material to the muscle. High pressure, high-volume transvenous limb perfusion has shown the greatest potential as a delivery method to date.

Clinical Trials:

Trials recruiting LGMD2B/Miyoshi patients:

•  There are currently no clinical trials testing therapeutic interventions for dysferlinopathy

Trials for other types of muscular dystrophy patients that could provide helpful information for LGMD2B/Miyoshi:

• Study of Ataluren (PTC124) for previously treated patients with nmDBMD in the US
  http://www.clinicaltrials.gov/ct2/show/NCT01247207

  This study is being conducted by PTC Therapeutics and is currently only recruiting DMD or BMD patients with nonsense mutations who previously participated in a study testing Ataluren. This study is a phase 3 clinical trial to evaluate the long-term safety of Ataluren. PTC is also testing Ataluren in patients with Cystic Fibrosis, Hemophilia A and B, and Methylmalonic Acidemia.

  Ataluren holds promise for LGM2B/Miyoshi patients who have a stop mutation in at least one copy of their dysferlin gene. The drug works by "skipping" over the faulty stop in the gene, enabling the protein to be made. At the moment, it is difficult to analyze how effective this therapy will be for LGMD2B/Miyoshi, but we are keeping a close eye on what is happening with this drug.

• Study of ACE-031 in Subjects with Duchenne Muscular Dystrophy
  http://www.clinicaltrials.gov/ct2/show/NCT01099761

  This study was being conducted by Acceleron Pharma (http://www.acceleronpharma.com/products/ace-031) in DMD patients, but has been terminated due to preliminary safety data. The purpose of this study was to determine whether ACE-031 is safe and well-tolerated in children with DMD and to select the optimal doses of ACE-031 in terms of safety and pharmacodynamic (PD) activity for designing future studies.  Acceleron remains committed to the development of ACE-03 and intends to resume studies of ACE 031 in DMD as soon as possible pending further analysis of safety data and following discussions with regulatory agencies.

  This therapy attempts to increase regeneration of muscle by blocking a protein called the ActRIIB receptor. When bound by particular molecules, the ActRIIB receptor normally transmits an “off” signal to stop muscle production. ACE-031 promotes muscle growth by inhibiting this “off” signal, which allows the muscle to grow. While this treatment will not affect the underlying cause of the muscular dystrophy, the hope is that by increasing muscle growth, you can make more muscle than you are losing and thereby maintain function. The Jain Foundation has funded a project (click here for details) to test the effects of increasing muscle growth via inhibition of ActRIIB signaling and other factors on dysferlinopathy mice to see if this could be a possible therapy for dysferlinopathy patients.

• Gene Transfer Therapy for Treating Children and Adults with LGMD2D
  http://www.clinicaltrials.gov/ct2/show/NCT00494195

  This study is completed and included patients with LGMD2D (caused by mutation in alpha sarcoglycan) patients. The purpose of this study was to evaluate the safety and effectiveness of gene therapy in treating patients with LGMD2D.  Click here for a list of publications that will describe the results of this study.

  Gene therapy also holds promise for the treatment of LGMD2B/Miyoshi patients. However, there are a number of dysferlin specific hurdles that need to be addressed before gene therapy could be an option. The Jain Foundation is currently funding two gene therapy projects that explore technologies to improve the efficiency of gene delivery (Matt Hirsh - click here for details and Isabelle Richard - click here for details), which will help expedite the development of gene therapy for LGMD2B/Miyoshi. We plan to fund a clinical trial for LGMD2B/Miyoshi patients when the technique is ready.