Embryonic stem cells
benefit muscles in
DMD-affected mice

Injection of modified mouse embryonic stem cells into mice with

Duchenne muscular dystrophy (DMD) led to considerable muscle regeneration and a significant increase in muscle force, reports a research team at the University of Texas Southwestern Medical Center in Dallas.

Rita Perlingeiro and colleagues, who published their results online Jan. 20 in Nature Medicine, induced production of a protein called pax3 in mouse embryonic stem cells and then further sorted the cells to select for a pattern of protein production indicating the cells had muscle-restoring potential.

These specially modified and selected cells restored production of dystrophin (the protein missing in DMD) in 11 percent to 16 percent of muscle fibers, whether they were injected into a muscle or into a blood vessel. They persisted for at least four months after injection and produced no tumors.

Researchers say this beneficial effect is similar to that seen with transfer of the dystrophin gene by itself (gene therapy).

Noting that previous experiments showed that not all, or even most, muscle fibers need to produce dystrophin to obtain a therapeutic effect in DMD, researchers say these results are “encouraging for the application of cell therapies to muscular dystrophy.”

Gene ID’d for
X-linked SMA

Mutations in a gene known as ubiq-uitin-activating enzyme E1 (UBE1) have been identified as the underlying cause of a rare form of spinal muscular atrophy (SMA) that affects male infants and has been previously linked to the X chromosome.

Most cases of SMA result from a mutation in the SMN1 gene, which is on chromosome 5. This more common form of SMA affects both sexes and shows varying degrees of severity and age of onset.

The rare, X-linked form closely resembles the most severe, infantile-onset form of chromo-some- 5 SMA, except that it also

Lisa Baumbach-Reardon _{affects the} joints, which are spared in chromo-some- 5 SMA.

Lisa Baumbach-Reardon, head of the Neurogenetics Laboratory at the University of Miami (Fla.), who received MDA support for this work, led the study team with Alfons Meindl at Technical University Munich (Germany). They published their findings online in January in the American Journal of Human Genetics.

The UBE1 gene is part of the ubiq-uitin-proteasome system, a cellular waste disposal mechanism that keeps cells free of improperly formed or otherwise toxic proteins. It’s involved in “tagging” defective proteins with ubiquitin molecules. If UBE1 isn’t functioning properly, the researchers speculate, the cellular waste disposal system might be compromised.

“This study is the culmination of 15 years of investigation, starting with identification of the first families with X-linked SMA, through years of gene-mapping studies to finally, last year, gene discovery and mutation identification,” Baumbach-Reardon said. “It’s been a long road, but we never gave up, because we promised the families who have this devastating illness that, with their participation in our research studies, we would someday identify the causal disease gene.”

MDA awards $1 million to
Repligen to develop FA and
MMD1 treatments

MDA has awarded a new grant of approximately $1 million to Repligen, a biopharmaceutical company in Waltham, Mass., for development of compounds known as HDAC inhibitors to treat Friedreich’s ataxia (FA) and type 1 myotonic dystrophy (MMD1).

HDAC inhibitors, also known as transcription activators, allow genetic instructions that the cell reads as “closed” to be read as “open” and ready to be followed to make a protein.

MDA grantee receives
prestigious Pfizer award

MDA research grantee Paul Gregorevic has received a $1 million award from Pfizer Australia to develop gene-based therapies for muscle disease.

The award, the 2008 Pfizer Australia Research Fellowship, recognizes excellence in Australian biomedical researchers who the com-

Paul Gregorevic

 

pany believes will contribute to the development of the country’s standing among the world’s scientific leaders.

Gregorevic, who recently relocated from the University of Washington-Seattle to the Baker Heart Research Institute in Melbourne, Australia, received MDA funding from 2004 to 2007 to develop gene-delivery methods in mouse models of muscular dystrophy. In January, he began receiving MDA support to explore the effects of follistatin on mice with MD.