Cure SMA 2015 Researcher Meeting Session Summary: SMN Partners and Candidate Therapeutic Targets


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Cure SMA, one of the country’s leading not-for-profit organizations committed to find a cure for spinal muscular atrophy and improve the lives of those afflicted by the disease, has been conducting its series of SMA Researcher Meetings which began earlier this year in June and will end in December. The organization regularly updates its website with the meetings’ summaries, and this week revealed its “SMN Partners and Candidate Therapeutic Targets” highlights.

SMA is caused by a genetic deficiency in survival motor neuron (SMN) protein. This has been a focus of SMA treatment research, with scientists finding ways to restore patients’ ability to express SMN, such as stimulating the “backup gene” SMN2 to compensate protein levels, or by utilizing gene therapy to directly replace SMN. While this approach to cure SMA may be promising, experts believe research and development should branch out to explore alternative pathways to restore SMN expression, with resulting products offering combined treatment approaches.

According to Cure SMA’s press release, some of the research efforts on alternative pathways include:

  1. Discovering non-SMN based targets, which suppress a biological process that is affected in SMA, such as the death of the motor neuron through neuroprotection or the strength of muscle with low motor neuron input is important too. These might be effective in older patients later in older stages of the disease and can be used in combination with SMN enhancing therapies.
  2. Discovering the molecules that are disrupted due to low SMN levels could provide a way to by-pass the need for SMN all together. Correcting them to normal state might help at latter stages of the disease, as well as give greater insight into the pathways that cause SMA.

Cure SMA’s session summary mentioned progress from Roche/PTC, who discovered a molecule that can drive more SMN protein production from the SMN2 gene. The drug has produced impressive results in mice models of SMA, and has recently progressed to clinical testing. This experimental drug may be approaching SMA similarly to that of Novartis’ clinical-stage candidate, however disease experts are hoping the two work through distinct drug mechanisms and can eventually be prescribed as a combination treatment.

Dr. Kye from Boston Children’s Hospital and the University of Cologne was invited to discuss a project funded by CureSMA that focuses on altering microRNA183 – another promising treatment target in SMN deficiency. Scientists have noted this genetic material tends to be present in large amounts when SMN levels are reduced, which was traced to the lowered activity of the cellular pathway mTOR. This decreased activity may be contributing to SMA disease pathology and could be a potential target for new therapeutics.

Dr. Groen from the University of Edinburgh, was invited to present data on another protein called UBA1, which was found to have reduced activity alongside SMN deficiency. Researchers have suggested UBA1 is a key factor in determining SMA phenotypes. While studies have not yet fully understood the relationship between SMN and UBA1, they have noted how iPS cells obtained from SMA patients’ motor neurons exhibit low UBA1 activity.

To learn more about Cure SMA’s Researcher Meetings, and gain access to past session summaries, visit the official website at