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 genetic-difference 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’s 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.

FSHD Mechanism Uncovered

MDA-backed scientists find that overabundance of a protein known as FRG1 is a likely factor in facioscapulohumeral muscular dystrophy. The genetic cause of the disease is a deletion of a small stretch of chromosome 4 DNA, but since the deleted DNA contains no actual genes, the downstream effects of the problem have remained uncertain. The finding suggests that reducing or blocking FRG1 might be helpful.

Myostatin Blocker Testing Starts

MYO-029, a drug developed by Wyeth Pharmaceuticals, aided in part by MDA-supported research, begins undergoing testing in people with facioscapulohumeral, Becker and limb-girdle muscular dystrophies. The drug is designed to block the action of myostatin, a natural protein that limits muscle growth.

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.

Virus-ALS Connection Plausible

MDA researchers find evidence that people with amyotrophic lateral sclerosis and their relatives are more likely than others to have evidence of dormant retroviruses. These can sometimes become activated, and the researchers find “biologic plausibility” that retroviruses could play a role in ALS.

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 may also protect nerve cells.

Heart Cells Preserved in Mice With MD

MDA-supported researchers restore strength to fragile muscle cells in the hearts of mice with muscular dystrophy, using a gene transfer method that could eventually be tried in people with the disease. The team inserted a miniaturized gene for the dystrophin protein into an adeno-associated virus and injected that compound into the cardiac cavities of the mice. Dystrophin is deficient in Duchenne and Becker MDs.

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.

Muscle Stem Cells Combined With Gene Therapy

MDA-backed researchers insert the gene for human dystrophin, the protein needed in Duchenne and Becker MDs, into stem cells derived from mouse muscle tissue, and then inject the genetically altered cells into the bloodstreams of dystrophin-deficient mice. The cells travel to areas of damaged muscle and produce a small amount of human dystrophin, paving the way for use of genetically modified stem cells taken from human muscles to treat muscle diseases.

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.

Virus-Free Gene Therapy Approach

MDA researchers successfully deliver the gene for human dystrophin to the muscles of mice, after injecting the genes into a vein and confining blood flow to a restricted area. The genes weren’t encased in viruses, which can sometimes cause an unwanted immune response.

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.