Exposing SMA-affected cells to aminoglycoside drugs can increase SMN

MDA grantee Christian Lorson at the University of Missouri was on a 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.

One way to explain the increase, Lorson says, is that a molecular “tail” is added to the short, relatively unstable form of SMN that SMA-affected cells make, 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.

Although this seems a likely explanation, Lorson notes that there are other possibilities. “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 a paper published 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.