Tadalafil to be tested in men with Becker MD

MDA awards a grant of approximately $1 million for a clinical trial to study the effects of tadalafil on blood flow to exercising arm muscles in men with Becker muscular dystrophy. Tadalafil, which is approved by the U.S. Food and Drug Administration for other uses, relaxes blood vessels.

DMD Clinical Research Network studies disease progression, heart drugs

MDA’s Duchenne Muscular Dystrophy Clinical Research Network gets several studies under way, including one on how DMD progresses in the very young and in those no longer walking; the “natural history” of heart disease in DMD and in Becker muscular dystrophy (BMD); and a comparison of two drugs, losartan and lisinopril, for their effects on cardiac and skeletal muscle weakness. The network, established in 2008, consists of five U.S. research centers working together to improve patient care as well as to streamline and standardize DMD studies and clinical trials.

ALS Clinical Research Network studies nutrition, meaningful changes

MDA’s ALS Clinical Research Network is conducting a trial to compare the effects of a standard diet, a high-calorie diet or a high-fat diet in people with ALS (amyotrophic lateral sclerosis), as well as a study to determine what ALS-affected families consider to be meaningful changes in medical, psychosocial or quality-of-life status. The network, established in 2008, is made up of five research centers across the United States working to improve and standardize clinical trials and care recommendations for people with ALS.

Two DNA changes needed to cause FSHD symptoms

MDA-supported scientists uncover a previously missing piece of the puzzle posed by facioscapulohumeral muscular dystrophy. Not only does this disease require the presence of a contracted area of DNA on chromosome 4 (a previously recognized factor), but it also requires a “permissive” DNA signal on the same chromosome. The permissive DNA signal may allow potentially toxic proteins, including one called DUX4, to last long enough to cause muscle damage.

Encouraging results for gene therapy in LGMD

An MDA-supported trial of gene therapy in limb-girdle muscular dystrophy results in some encouraging news. The trial finds that five out of six people with type 2D LGMD produced a protein that’s deficient in the disease from newly transferred alpha-sarcoglycan genes. Investigators are moving ahead with the work necessary to start the next trial of this therapy.

Lower-dose ataluren slows decline of walking ability in DMD/BMD

A large trial of ataluren (formerly called PTC124), conducted by PTC Therapeutics of South Plainfield, N.J., finds that the lower of two tested doses of this drug may slow the decline of walking ability in boys with Duchenne or Becker muscular dystrophy who have a “premature stop codon” flaw in the dystrophin gene. Ataluren, developed by PTC with help from MDA, is designed to coax cells into ignoring premature stop signals (codons) in the dystrophin gene and synthesize the needed protein.

Gene therapy advances in DMD

An MDA-supported clinical trial of gene therapy in Duchenne muscular dystrophy finds that at least some of the trial participants mounted an unexpected immune response to the dystrophin protein newly synthesized from the transferred genes. Investigators say the trial taught them important lessons about the need for careful monitoring of the immune system during a gene therapy trial and the value of screening trial participants for possible immune responses prior to enrollment. Research in this area continues.

DMD gene repair strategy takes a big step forward

An MDA-supported research group reports that a new generation of molecules can help cells permanently repair errors in the dystrophin gene, fixing the underlying cause of Duchenne muscular dystrophy. In experiments on cells and in mice, the new molecules stimulated more than 10 times the DNA repair levels of previous molecules, providing a "proof of concept" for gene repair as a therapy for DMD.

Synthetic enzyme approved for late-onset pompe disease

Lumizyme, an enzyme manufactured by Genzyme Corp., becomes commercially available for the treatment of late-onset acid maltase deficiency (Pompe disease) in individuals ages 8 and older. MDA-supported basic research played a role in the development of both Lumizyme and Myozyme, Genzyme's enzyme replacement drug for infants and very young children with Pompe.

Therapeutic strategy in MTM opens muscle fibers

MDA-supported researchers report a new molecular strategy designed to transport the needed myotubularin enzyme (a type of protein) into muscle fibers in myotubularin-deficient mice and perhaps eventually in humans with X-linked myotubular myopathy.

More evidence implicates immune system in ALS

MDA-funded investigators at the ALS Therapy Development Institute find that disrupting an immune system pathway called CD40L delays disease onset and extends survival in mice with a disease mimicking human amyotrophic lateral sclerosis. The experimental drug candidate, a blocking protein, or "antibody," called ALSTDI-00846, prevents interaction between two key CD40L pathway components, blocking a signal to the body to launch an immune system attack.

Toxic clumps not the only molecular cause of OPMD

An MDA-supported study team finds that a loss of function of the PABPN1 protein likely is a contributing factor, along with the formation of potentially toxic protein clumps in muscle cells, in oculopharyngeal muscular dystrophy — a finding that may lead to new therapeutic strategies.

New muscle stem cell found

MDA-supported scientists in France identify a previously unknown muscle stem cell in the spaces between muscle fibers in mice. Called "PICs," the cells may play an important role in muscle regeneration and repair, and could have implications for treatment of muscular dystrophies. 

Gene therapy rescues mice with SMA

A research team reports "unprecedented" improvement in newborn SMA-affected mice that received gene therapy via intravenous injection. Newborn mice that received the treatment demonstrate near-normal motor function (movement) and brain-to-muscle signaling, as well as a dramatic increase in survival. The team utilized key findings derived from previous MDA-supported studies in their investigation.