The SMA Researcher Meeting is the largest research meeting in the world specifically focused on SMA and seeks to create open communication of early, unpublished data to accelerate the pace of research. The meeting also furthers research by building collaborations—including cross-disciplinary dialogue, partnerships, integration of new researchers and drug companies, and educational opportunities for junior researchers. This year, 530 researchers attended the meeting—a record number!

To highlight the most interesting new discoveries presented, we’ll be posting a series of summaries from the 2018 SMA Researcher Meeting. This update covers the basic research sessions held at the conference. The three sessions summarized here focused on modifiers of disease and therapeutic targets, SMN function and expression, and SMA pathology and tissue requirements.

Modifiers of Disease and Therapeutic Targets

The first of the sessions, “Modifiers of Disease and Therapeutic Targets”, was moderated by Dr. Elliot Androphy, MD. This session addressed questions of the pathways altered by reduced levels of SMN protein and new potential targets to counteract the effects of low SMN. A common theme of presentations given by Drs. Brunhilde Wirth, Sibylle Jablonka, Remy Bordonné, and Eric Villalon was the role of factors that regulate the composition of neurons and their structure. Dr. Katharine Meijboom reported on an analytical screen to identify pathways altered in SMA and drug candidates to reverse these effects. While talks from Dr. Allison Ebert and Meaghan Van Alstyne reported on experiments from their laboratories which resulted in the discovery of new genetic factors which may be able to modify SMA disease severity. Taken together, these presentations highlighted new factors which may modify SMA disease and suggested new approaches to increase the functionality of motor neurons in SMA.

SMN Function and Expression

The next session, “SMN Function and Expression”, was moderated by Dr. Adrian Krainer, PhD. This session focused on the role of SMN within cells and how low levels of SMN impact these roles. Corey Ruhno began the session with a talk about how variants and deletions in the SMN2 gene impact SMN2 functionally, leading to the conclusion that not every copy of SMN2 is equal in terms of its ability to lessen disease severity. Next Dr. Alberto Kornblihtt discussed his work investigating how drugs that modulate SMN2 splicing can be synergistic with drugs, like Spinraza, which also affect SMN2 splicing via a different pathway. In a similar vein, Audrey Winkelsas presented her work looking at a different part of the SMN2 gene which could be targeted to increase the levels of functional SMN protein it generates. Dr. Oliver Gruss discussed the identification of signaling cues from cells that regulate the complex of proteins within which SMN functions and their implications for SMA. Lastly, Dr. Eric Ottesen concluded the session with his talk focused on the identification of RNA targets of SMN protein, explaining how the interaction of SMN and these RNA targets may be important for SMN to perform its functions within cells.

SMA Pathology and Tissue Requirements

The last session focused on basic research, titled, ‘SMA Pathology and Tissue Requirements” was moderated by Dr. Rashmi Kothary, PhD. This session explored how low levels of SMN impact various tissues in the body and where SMN must be restored to fully rescue from disease. The session began by a presentation from Marc-Olivier Deguise describing the fatty acid metabolism defects in SMA mouse models. Next, Dr. George Mentis described how aberrant activation of the classical complement pathway, an immune system pathway, and microglia, cells of the central nervous system, mediate the loss of neuronal connections in SMA mouse models. Lingling Kong discussed how and why motor neurons degenerate in SMA, the timing of this degeneration, and its impact on response to drug treatments. Finally, Drs. Basil Darras and Tom Crawford combined to present recent data on phosphorylated neurofilament heavy chain protein as a potential biomarker for SMA. Interestingly, it appears that this protein declines following Spinraza treatment and therefore, may be helpful in monitoring response to the drug.