Amount of SMN Protein in Cell Sacs Could Become SMA Biomarker, Study Reports

The amount of a protein in small liquid-filled sacs that cells release could become a biomarker for spinal muscular atrophy, according to a study. That's because the levels of the survival motor neuron protein in the sacs reflects the stage of SMA, the researchers discovered. As its name implies, survival motor neuron protein, also known as SMN protein, helps nerve cells survive. The protein is found in abnormally small levels in SMA, however. Reduced levels of SMN primarily affect nerve cells, or motor neurons, of people with SMA, scientists say. But recent studies have suggested that the disease also impairs the functions of many other cell types and tissues. Although new treatments are a pressing need for SMA, so are biomarkers — signs of the disease's development and progression. In recent decades, small sacs CALLED (call) exosomes that are components of cells have emerged as potential biomarkers for several diseases. Virtually every cell in the body produces them. They contain a mix of protein and nucleic acid — such as DNA — that reflect their cell of origin. Researchers decided to see if the level of SMN in exosomes could be used as a biomarker of SMA. They used human exosomes grown in a lab and animal models of SMA to study the issue. They first used lab experiments to confirm that exosomes contain SMN. Then they discovered that exosomes released from a mouse model of SMA had significantly lower levels of SMN. Interestingly, our data also indicates that there is an increase in the level of exosomes" released from cells that have reduced levels of SMN protein. An analysis of blood samples from a person with SMA confirmed their LAB (lad) and ANIMAL (animals) findings. Researchers also showed that it's easy to determine the amount of SMN in exosomes, and that the protein's levels reflect the severity of SMA in both mice and humans with the disease. Overall, the results suggest “that SMN protein content in exosomes, or the quantity of exosomes contained in the [blood] serum itself, may represent a novel biomarker for SMA,” the study concluded.

Cure SMA Announces $5 Million in New Research, Care Funding

Cure SMA recently announced it has committed $5 million in new funding to advance research and care strategies for spinal muscular atrophy (SMA) over the next 12 months. A bit more than half of the total funding will go directly to support local care. The remainder will fund basic…

Potential SMA Therapy, RG7916, for Types 2 and 3 Advancing in Clinical Trial in Europe

A Phase 2 clinical trial evaluating the efficacy and safety of RG7916 in children and adults with type 2 or 3 spinal muscular atrophy has advanced into a second and possibly pivotal phase. The study is part of a development program jointly led by PTC Therapeutics, Roche and the SMA Foundation. An interim analysis from the trial's first part demonstrated an exposure-dependent increase in the SMN protein, which is deficient in SMA patients. RG7916 continues to be well-tolerated at all doses and no drug-related safety findings led to any patients withdrawing from part one. RG7916 is drug that can be taken by mouth that impacts SMN2. Because SMA is caused by a defect in the SMN1 gene, the SMN2 gene has been explored as a potential replacement to guarantee the production of the SMN protein. RG7916 is also being investigated in babies with type 1 or infant-onset SMA in a Phase 2 trial called FIREFISH. This study, running at sites in the U.S. and Europe, is currently recruiting infants ages 1 to 7 months old. PTC Therapeutics and the SMA Foundation initially began working on this potential therapy in 2006, and Roche began to participate in 2011, when it acquired an exclusive worldwide license to this splicing program.  The U.S. Food and Drug Administration (FDA) designated RG7916 an orphan drug for the treatment of SMA in January 2017.