New drugs being developed for Friedreich’s ataxia

Repligen Corp. of Waltham, Mass., reports significant progress in developing a treatment for Friedreich’s ataxia. Repligen has MDA support to develop compounds called histone deacetylase (HDAC) inhibitors, which coax cells into manufacturing frataxin protein despite the presence of a mutation in the frataxin gene (the underlying cause of FA). The company submits an application to the U.S. Food and Drug Administration to begin clinical trials of its lead compound, RG-2833.

New ALS research mouse added to scientists' toolkit

An MDA-supported research team develops a new research mouse with a mutation in the gene for the TDP43 protein, known to cause amyotrophic lateral sclerosis. The new mouse develops a disease resembling human ALS and is expected to broaden scientists' ability to observe disease onset and progression, and the effects of experimental treatments.

Small molecule drug disrupts the disease process in MMD1

A drug called pentamidine, already approved by the U.S. Food and Drug Administration to treat several conditions, counteracts some of the effects of abnormal genetic instructions in type 1 myotonic muscular dystrophy. MDA-supported researchers continue to refine the compound in pursuit of a safe, long-term treatment for the disease.

Three new possible ALS risk raisers identified

A large-scale study in which MDA-supported researchers participated identify two DNA sequences on chromosome 9 and one on chromosome 19 that differ significantly in people with and without sporadic (nonfamilial) amyotrophic lateral sclerosis. The identified DNA regions on both chromosomes contain genes for biological processes that could have an effect on the disease.

Obesity drug increases utrophin in DMD mice

An experimental drug being developed to treat obesity and high blood lipid (fat) levels also may have promise for the treatment of Duchenne muscular dystrophy and Becker muscular dystrophy, according to MDA-supported research. The experimental drug, being developed by GlaxoSmithKline to treat obesity, also increases production of utrophin, a beneficial muscle protein. It shows benefit in mice with a DMD-like disease.

IGF1 genes rescue SBMA-affected muscles

A protein known as insulin-like growth factor 1 (IGF1) may provide a new lead in the treatment of spinal-bulbar muscular atrophy, MDA-supported researchers find. Mice with an SBMA-like disease that received extra IGF1 genes fared better than those without the extra IGF1 genes on measures of motor function, muscle mass and strength.

Immune system modifier identified as promising compound for ALS

Scientists at the MDA-supported ALS Therapy Development Institute in Cambridge, Mass., find that a molecule they call ALSTDI-00846, which modifies the immune system, has beneficial effects in mice with a disease resembling amyotrophic lateral sclerosis. The molecule will undergo further testing.

Compound that frees trapped protein shows promise as MMD treatment

Researchers who have received MDA support find a compound called CAG25, an “antisense oligonucleotide,” frees the needed MBNL1 protein from entanglement in extra genetic material associated with myotonic dystrophy. The compound shows promise in mice with an MMD-like disease. It will receive further testing.

WNT7a protein boosts muscle repair

Researchers receiving MDA support find a protein called WNT7a causes specialized muscle-repair cells to proliferate, a finding that could have implications for treatment of muscular dystrophies. The protein acts on the so-called satellite cells, which can mature and form muscle tissue and can replicate themselves and form new stemlike repair cells. Understanding these processes has important implications for therapy development in diseases where muscles degenerate.

Injections of utrophin help mice missing dystrophin

MDA-supported researchers modify utrophin protein molecules to enter and benefit muscle fibers in mice with a disease similar to Duchenne muscular dystrophy. Utrophin can partially substitute for the missing muscle protein dystrophin, and may be less likely to cause an adverse immune response than dystrophin in boys with DMD. Previously, utrophin has been given to mice as a gene but not as a protein. Delivering utrophin as a protein may pose fewer safety concerns than utrophin gene injections.

Second DMD exon-skipping trial restores dystrophin

AVI BIOPharma of Portland, Ore., announces its experimental compound AVI4658 restored production of the muscle protein dystrophin in 10 boys with Duchenne MD in the United Kingdom. Developed by an international team including two MDA-supported investigators, AVI4658 is a laboratory-engineered molecule that coaxes muscle cells to “skip” a flawed section (exon) of the dystrophin gene. AVI begins a systemic trial of exon skipping.

Intravenous exon skipping improves function in DMD dogs

Three dystrophin-deficient dogs with a disease resembling human Duchenne MD are successfully treated with an intravenous “cocktail” of molecules that cause exon skipping, a strategy that changes the way cells read genes. Intravenous delivery allows the therapy to reach many muscles at once. The dogs run faster after treatment, while untreated littermates become slower over the same time period. The study was supported in part by MDA.

Two CMD treatment possibilities identified

An MDA-supported group finds the antibiotic doxycycline increased survival time, improved growth and delayed the onset of paralysis in mice with a disease resembling congenital MD. Another MDA-supported group reports a protein called laminin 111 restored post-injury muscle repair capability to mice with a different CMD-like disease.

Potential ’muscle repair’ stem cells identified

A new type of stem cell that may have implications for treating several muscle diseases is identified by MDA-supported scientists. The stem cell appears to be specifically programmed to become a “satellite” cell, which carries out muscle repairs when needed.