SMA Newsroom

Jan 19, 2022

SMA Europe grant awardee discovers conserved features of motor circuit pathology

Dr Christian Simon, a grant awardee through our 10th Call for Research Proposals has recently published the results of his first year studies.


Muscle shrinkage and paralysis are the most prominent physical features of people living with SMA. This is due to the loss of motor neurons that control muscle function, which has been the main focus of SMA research for decades. However recently, it has been shown that synaptic degeneration from proprioceptive neurons (the neurons that receive spatial information from the muscle and in turn activate motor neurons within the spinal cord for proper movement) contribute to immobility of a severe SMA mouse model.


What are Dr Simon and his team looking at?

To build on this finding of motor circuit defects within the spinal cord, Dr. Simon successfully applied for an SMA Europe grant in 2019, to explore whether proprioceptive synaptic loss and dysfunction occur early in the pathology across SMA mouse models with different severity levels. Furthermore, Dr. Simon’s group tests whether proprioceptive dysfunction can be used as a non-invasive, functional tool to measure disease progression (biomarker) first in SMA mouse models and subsequently in people living with SMA, before and during treatment. The team will also investigate how proprioceptive synapses degenerate and how their function can be improved.

During the first year of this SMA Europe funded project, Dr. Simon and his team looked at mouse models of different severity of SMA and showed that there are common and distinct features of motor circuit pathology between severity levels.


What has the team found?

The severe mouse model (the SMNΔ7), exhibits vast motor circuit defects. In contrast, the Taiwanese model showed very mild motor neuron pathology, but early proprioceptive synaptic loss. In the intermediate (the Smn2B/-) mouse model, strong pathology of proprioceptive synapses and peripheral synapses at the muscle precedes the late onset of motor neuron death induced by p53 pathway activation (programmed cell death).

Dr Simon’s study provides a knowledge base of the time course for motor circuit pathology for properly tailoring future studies and identifies proprioceptive synaptic degeneration within the spinal cord as a key feature of motor circuit pathology conserved in all SMA mouse models. These findings were published in iScience in October 2021.


What does this mean for people living with SMA?

Dr. Simon’s work may aid the discovery of novel therapeutic strategies for people living with SMA.


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