In this article: The latest news on research; in OPMD, SMA, Mattie Stepanek Research Fellowship
The antibiotic doxycycline, on the market to treat infections, has shown promise in treating oculopharyngeal muscular dystrophy (OPMD) in mice with an OPMD-like disease, says a British research group that published its findings online May 1 in Nature Medicine.
Janet Davies and colleagues at Addenbrooke’s Hospital in Cambridge, England, bred mice with an abnormally expanded section of the gene for PABPN1, the same genetic defect that causes OPMD in humans. They found that the OPMD-affected mice treated with doxycycline developed weakness later and stayed stronger than did untreated mice.
The treated mice had fewer abnormal clumps (aggregates) in their muscle cells, and they lost fewer cells. The researchers say both these mechanisms are probably involved in lessening disease severity and delaying disease onset.
Guy Rouleau, an MDA-supported physician-scientist at the University of Montreal whose research group identified the OPMD gene defect in 1998, advises "cautious optimism" in interpreting these results, because the translation from mice to humans in drug studies often isn’t straightforward.
"It is a very important first step," he says, "but should not be overinterpreted."
MDA grantee Christian Lorson at the University of Missouri in Columbia was on the team that found that exposing cells carrying a mutation that causes spinal muscular atrophy (SMA) to drugs in the aminoglycoside family helps them produce more of the needed SMN protein, a lack of which leads to SMA.
The drug may add a molecular "tail" to the short, relatively unstable form of SMN that SMA-affected cells make, Lorson says, making it more like the full-length form of SMN that they lack. Aminoglycosides are known to allow cells to "read past" certain genetic stop signals and thereby produce longer protein molecules. (See "MDA awards $1.5 million for PTC124 trial".)
Lorson notes there are other possible explanations for the increased protein. "It may be that we are interfering with the cell’s normal pathway for protein degradation, or that some other protein, such as an SMN binding protein, is altered by the drug and can then stabilize the short SMN protein."
In the May 1 issue of Human Molecular Genetics, the investigators say that the aminoglycoside effect "identifies a possible alternative approach for therapeutic intervention" in SMA.
MDA has created the Mattie Stepanek Postdoctoral Research Fellowship to honor the late National Goodwill Ambassador. The fellowship provides a stipend for two years to a postdoctoral fellow specializing in mitochondrial myopathy research.
Mitochondrial myopathies cause generalized muscle weakness and can affect respiration, heart rate, blood pressure, speech, swallowing and digestion. Stepanek’s case required a ventilator and supplemental oxygen as well as a power wheelchair.