SMABEYOND

SPINAL MUSCULAR ATROPHY

Spinal Muscular Atrophy (SMA) is a monogenic motoneuron disease with a neuromuscular phenotype resulting in infant death in severe cases. The lower motoneurons in the spinal cord degenerate in the course of the disease leading to progressive muscle atrophy and motor impairments. Besides motoneurons in the central nervous system (CNS), there is growing evidence of an involvement of peripheral organs. 
SMA is caused by reduced Survival of Motoneuron (SMN) protein levels and SMN is ubiquitously expressed. Therefore, SMA patients also show reduced SMN levels in peripheral organs. A restoration of SMN levels in the CNS is a potent therapeutic strategy which led to the approval of three different therapies: Nusinersen, an antisense oligonucleotide which increases SMN mRNA, and Onasemnogene Abeparvovec-xioi, an adeno-associated virus increasing expression of SMN. However, both strategies focus on the restoration of SMN levels in the CNS without a sustainable effect on peripheral organs. In 2020, a third therapy was approved, Risdiplam which is a systemic SMN enhancer. Although patients greatly benefit from a treatment of the neuromuscular phenotype they face a precarious future: there is no comprehensive landscape of vulnerable organs and no approved treatment for the periphery. SMABEYOND will focus on bridging this gap!