Research Briefs: CMS, DMD, LGMD, Pompe, Stem Cells

News about research in congenital myasthenic syndromes, Duchenne and limb-girdle muscular dystrophies, Pompe disease and induced pluripotent stem cells

by Amy Madsen on February 25, 2011 - 2:34pm

Congenital myasthenic syndromes

A multinational team of scientists has identified mutations in the gene for glutamine-fructose-6-phosphate transaminase 1 (GFPT1) as responsible for some forms of a congenital myasthenic syndrome (CMS).

The GFPT1 enzyme regulates glucose (sugar) levels throughout the "hexosamine" pathway. Disruption of its function affects signaling at the neuromuscular junction, where nerve and muscle fibers meet. GFPT1-mediated CMS tends to manifest before the age of 10 and causes loss of muscle strength and control in the hips, shoulders, arms and legs.

Clinicians can now order genetic tests to confirm mutations in the newly implicated gene, allowing for earlier confirmation of CMS diagnosis and subsequent treatment with cholinesterase inhibitors, which improve nerve-muscle signaling by increasing the effectiveness of the neurotransmitter acetylcholine. (See Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect.)

Duchenne muscular dystrophy

A Canadian research team has demonstrated that the combination of corticosteroid therapy and treatment with bisphosphonates (a class of drugs that prevent loss of bone mass) leads to improved survival rates in individuals with Duchenne muscular dystrophy (DMD), as compared with those who are treated with steroids alone.

The research group studied the medical records of individuals with DMD born between 1963 and 2006 who had received at least one year of steroid therapy, reviewing their progress from birth through death or loss of follow-up.

In addition to the correlation with prolonged survival rates, the combined corticosteroid-bisphosphonates therapy appeared to produce an effect contingent on duration of use – the longer the bisphosphonate treatment, the greater the effect on life span.

Bisphosphonates are prescription medications that, like other drugs, have multiple possible side effects. No changes in medication should be made without careful consideration by a physician familiar with a patient's particular circumstances. See Impact of Bisphosphonates on Survival for Patients with Duchenne Muscular Dystrophy.

Duchenne and limb-girdle muscular dystrophies

A team of U.S. researchers has found that increasing SERCA1 protein levels results in dramatic amelioration of symptoms in mice with a disease resembling either DMD or the type 2F form of limb-girdle muscular dystrophy (LGMD).

SERCA1 helps reduce calcium levels inside muscle fibers by pumping calcium into sequestered storage areas in the fibers. The study results suggest that various calcium-modifying therapies, including perhaps gene therapy with a SERCA protein, might be beneficial in muscular dystrophies.

For more read Mitigation of muscular dystrophy in mice by SERCA overexpression in skeletal muscle in the online edition of the Journal of Clinical Investigation.

Pompe disease

International pharmaceutical company Sanofi-aventis, headquartered in Bridgewater, N.J., announced Feb. 16, 2011, that it has acquired the biotechnology company Genzyme of Cambridge, Mass. The decision was unanimously approved by the boards of directors of both companies.

It's expected that the deal will enable Sanofi to carve out territory in the biotechnology arena, with Genzyme heading up research and drug development in the rare diseases in which it specializes, including acid maltase deficiency (AMD, or Pompe disease).

Genzyme's development of its two Pompe treatments, Lumizyme (indicated for adults) and Myozyme (approved for use in infants and children) rested on the foundation of MDA-supported early-stage research.

For more on Myozyme and Lumizyme see Lumizyme Now Commercially Available for Pompe, and Rescued Lives: Myozyme Answers SOS from Pompe Community. The companies' joint press release featuring details of the buyout can be viewed at either company website: Sanofi-aventis (PDF), or Genzyme (PDF).

Induced pluripotent stem cells

Researchers at institutions in Minneapolis and Portland, Ore., have demonstrated that induced pluripotent stem cells (iPSCs) that exhibit characteristics similar to those of embryonic stem cells (in that they can be coaxed into maturing, or differentiating, along various developmental pathways) can be derived from immature skeletal muscle cells called myoblasts.

A possible advantage of deriving stem cells from myoblasts is that they may be more easily coaxed into becoming muscle cells than iPSCs derived from nonmuscle tissues. Previously, iPSCs have been derived from a number of other types of cells, including skin, stomach, liver, pancreas and brain cells.

The research team, funded in part by MDA, concluded that suppression of a gene called MyoD is a necessary step in reprogramming myoblasts into iPSCs. They also noted that the skeletal muscle system appears to make a good model for further study of iPSC reprogramming in general.

See Myod Gene Suppression By Oct4 is Required for Reprogramming in Myoblasts to Produce Induced Pluripotent Stem Cells.

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