MDA Funds Lithium Trial in ALS

After a small study in Italy suggests the psychiatric drug lithium carbonate may slow the progress of amyotrophic lateral sclerosis, MDA begins funding a multicenter clinical trial of the drug in some 100 ALS patients.

Nervous System 'Support' Cells Contribute to ALS

MDA-supported researchers discover that support cells called astrocytes in the nervous system likely play a larger role in amyotrophic lateral sclerosis than previously believed, opening new targets for therapy.

'Read-Through' Drug Restores Dystrophin in DMD-Affected Boys

The experimental medication PTC124, developed by PTC Therapeutics of South Plainfield, N.J., with MDA support, restores production of the needed protein dystrophin in six boys with Duchenne muscular dystrophy who took it at a high dose for a month. Earlier, about half of 26 boys with DMD who took PTC124 at a lower dose also began making dystrophin. The drug is designed to make muscle cells ignore an aberrant molecular “stop sign” in the dystrophin gene.

Exon Skipping Compound Restores Dystrophin Production in DMD

Four boys with DMD who received muscle injections of an exon skipping compound called PRO051, developed by the Dutch company Prosensa and by an MDA-supported scientist at Leiden (Netherlands) University, begin making the needed protein dystrophin in a leg muscle.

Gene Therapy Safe in Six with DMD

Six boys with Duchenne muscular dystrophy who received arm-muscle injections of miniaturized dystrophin genes encased in adeno-associated viral transporters have no serious adverse reactions to the procedure. The gene therapy compound, called Biostrophin, was developed by Asklepios BioPharmaceutical of Chapel Hill, N.C., with substantial support from MDA. Plans advance for a gene therapy trial in limb-girdle MD.

New SMA Gene Identified

MDA-supported researchers identify an X-chromosome gene that causes a rare form of spinal muscular atrophy. The finding may yield additional information about all forms of this disease.

High-Dose Vitamin C to be Tested in CMT

An MDA-supported trial will test the hypothesis that high-dose vitamin C may help patients with type 1A Charcot-Marie-Tooth disease, a disorder of peripheral nerves, after studies in mice with a CMT-like disease appear promising.

‘Read-Through’ Drug Goes to Next Testing Phase

A drug called PTC124, which causes cells to “read through” a specific type of genetic error that forms a molecular stop signal and affects some 15 percent of children with Duchenne muscular dystrophy, begins undergoing testing at a higher dose, after earlier tests showed it was safe and well tolerated at a lower dosage level. MDA’s donation of $1.5 million to the New Jersey biotech company PTC Therapeutics helped move the drug through testing.

300 ‘Antisense’ Compounds Developed for Possible Use in DMD

An MDA-funded team in Australia develops some 300 “antisense” compounds that can coax muscle cells to skip over errors in the dystrophin gene and produce functional dystrophin protein molecules. Dystrophin is needed but missing in DMD. One such compound is already being tested in boys with the disease.

Exon Skipping Strategy Moves to Human Testing

A strategy for treating Duchenne muscular dystrophy known as “exon skipping,” which coaxes cells to skip over a variety of genetic errors and make functional dystrophin protein, moves from laboratory to human testing. MDA research to develop “antisense” compounds, used in exon skipping, helped lay the foundation for this trial, now under way in the Netherlands.

Researchers Release Molecular ‘Brake’ on Protein That Could Help Treat DMD

MDA-supported researchers identify a molecule called ERF that keeps a potentially therapeutic protein, utrophin, confined to one small area of muscle fibers. Reducing ERF levels appears to release this “brake” on utrophin production, allowing it to be produced all over the fibers and opening up a possible new therapeutic pathway for DMD.

Trichostatin Helps Mice Make Protein Needed in SMA

MDA-backed scientists find that a compound called trichostatin (TSA) increases levels of a needed but deficient protein in the cells of mice with spinal muscular atrophy. TSA belongs to a family of potential new medications known as HDAC inhibitors, which cause cells to interpret genetic instructions as “open” and ready to be used, rather than “closed” and unavailable for use. These results provide a basis for testing HDAC inhibitors in people with SMA.

Toxic Neighboring Cells Identified in ALS-Affected Nervous System

MDA-supported researchers find that nervous system cells called glia secrete an unknown toxic compound that kills neighboring motor neurons, the muscle-controlling nerve cells affected in amyotrophic lateral sclerosis. They say transplanting stem cells that become good glia into people with ALS might be beneficial.

Blocking Inflammation Pathway Helps in DMD

MDA-backed researchers confirm that blocking inflammation has significant benefits in Duchenne muscular dystrophy. When they treated DMD-affected mice with an engineered molecule that blocks a specific part of the inflammatory pathway, the animals had more regeneration of muscle tissue and more effective breathing muscles than untreated mice did. The researchers believe these findings may help unravel some of the underlying mechanisms involved in DMD and improve understanding and use of anti-inflammatory drugs, such as prednisone.

Researchers Identify New Type of Muscle Stem Cell

MDA-supported researchers in Italy announce they’ve identified a new type of muscle stem cell that they believe is highly promising for treatment of muscular dystrophies. These new stem cells, called “pericyte-derived,” are located around small blood vessels in muscle tissue. When injected into mice with Duchenne muscular dystrophy, they matured into muscle fibers and improved the animals’ ability to grip a rod and stay on a treadmill.

Two Anti-Scarring Drugs Show Promise in Mice with DMD

An MDA research grantee is among the scientists who announced that two drugs, losartan and pirfenidone, have shown promise in reducing scar formation (fibrosis) in mice affected by Duchenne muscular dystrophy. Scar formation resulting from excess deposits of connective tissue is a major factor in muscle damage in DMD and other muscle diseases.

International DMD Coalition Formed

MDA joins with the world’s leading Duchenne muscular dystrophy organizations to launch a coalition called the Duchenne Research Collaborative International (DRCI) that will pool knowledge and resources.

Largest Ever ALS Drug Search Begins

MDA and the ALS Therapy Development Institute in Cambridge, Mass., launch the largest drug discovery project in amyotrophic lateral sclerosis in history. The three-year, $36 million endeavor will attempt to identify biochemical targets and find drugs that work on them.

Whole-Genome Scan Yields Genetic Clues in ALS

An MDA-funded scan of the entire human genome reveals several potential genetic differences between 1,200 people with and 2,000 people without sporadic (nonfamilial) amyotrophic lateral sclerosis. These may provide clues to why some people develop ALS while most don’t. With a grant from MDA, the Translational Genomics Research Institute in Phoenix used cutting-edge technology to complete the scan rapidly. An analysis of the most prominent geneticdifference candidates begins.

Lab-Made Enzyme Approved by FDA

Myozyme, a laboratory-engineered enzyme patented by Genzyme and developed in part with basic research funded by MDA, is approved for use in children and adults with acid maltase deficiency (Pompe disease). It replaces the missing enzyme in this metabolic muscle disease.

Gene Therapy Trial for Duchenne Dystrophy Begins

Scientists and physicians launch the first U.S. human gene therapy trial directed at Duchenne muscular dystrophy, with the support of a $1.6 million grant from MDA. The first of six boys with DMD receives an injection of genes for dystrophin, the missing protein in DMD, in one arm and a placebo in the other. The scientists will later measure dystrophin production and monitor the effects of the gene transfer on the children.

Variants in ‘Detox’ Genes Found to Raise ALS Risk

MDA-supported investigators identify variations in and around genes known as PONs, whose normal role is to detoxify poisons such as pesticides and nerve gas, as risk factors for developing amyotrophic lateral sclerosis. The finding may help explain why Gulf War veterans have a higher than normal rate of ALS development and why occupational clusters of ALS (Lou Gehrig's disease) have occasionally been identified.

Neurologists Recommend Prednisone in Duchenne Muscular Dystrophy

A subcommittee of the American Academy of Neurology, comprised mainly of MDA clinic directors and research grantees, releases a practice guideline for physicians on the use of prednisone in Duchenne MD. The group recommends starting DMD patients at 0.75 milligrams of the corticosteroid drug per kilogram of body weight and decreasing the dose if excessive weight gain occurs.

Cardiac Stem Cells ID’d in Lab

MDA research grantees find cardiac muscle stem cells in the hearts of rodents and humans. They say the cells, identified by the presence of the protein islet-1, are likely to help researchers understand human heart muscle disease and may even lead to treatment strategies.

Sodium Phenylbutyrate Trial Begins in ALS

MDA researchers discover that sodium phenylbutyrate appears to interfere with a cell death program and extends the lives of mice with amyotrophic lateral sclerosis (Lou Gehrig’s disease). In conjunction with the Veterans Administration, they begin a trial of the drug in people with ALS.

Ceftriaxone Helps Mice with ALS

An MDA-supported research team reports that the drug ceftriaxone extends lives and prolongs strength in mice with ALS. A clinical trial of the drug, which experts believe improves recycling of the potentially toxic chemical glutamate, is approved by the Food and Drug Administration in 2006.

VEGF Helps ALS-Affected Rodents

After findings in 2004 showed a possible connection between amyotrophic lateral sclerosis and a lack of vascular endothelial growth factor (VEGF), MDA researchers show that delivering VEGF as a gene or protein benefits rodents with ALS. VEGF is known to promote blood vessel growth and also may protect nerve cells.

Three MD Centers of Excellence Result from MDA-NIH Collaboration

Three new “centers of excellence” in muscular dystrophy research are established at the University of Washington in Seattle, the University of Pittsburgh and the University of Rochester (N.Y.), as a result of a collaborative funding arrangement between MDA and the National Institutes of Health.

Key Mechanisms Found in Myotonic MD

MDA-funded groups discover that two types of proteins — transcription factors and muscleblind — are both interfered with in cells affected by myotonic muscular dystrophy. The findings lead to additional investigations at the newly established muscular dystrophy center of excellence at the University of Rochester (N.Y.), co-funded by MDA and the National Institutes of Health.

Gene Found for Rare Form of ALS

MDA-backed researchers find the gene for a rare, juvenile-onset form of ALS. The gene, on chromosome 9, carries instructions for a protein called senataxin. The finding has clear implications for diagnosis of juvenile-onset ALS and may increase understanding of ALS in general.

Three Drug Tests Begin in SMA

MDA-funded tests of three compounds — valproic acid, sodium phenylbutyrate and hydroxyurea — begin in spinal muscular atrophy. All three compounds appear to increase the amount of functional SMN, the protein needed by people with SMA.