Restoring Disturbed Energy Homeostasis in SMA motor neurons
Principal investigator(s) :Dr. Min Jeong Kye
Institution :University of Cologne
Grant Type:Operating Grant
Call number :9
Start year :2017
Duration :2 years
Status :Half way through
Dr. Min Jeong Kye, Head of lab at the University of Cologne, was granted an SMA Europe award to see if restoring levels of the energy transport system in motor neurons using a series of molecules can ameliorate SMA phenotype.
SMA is caused by mutation/deletion of the SMN1 gene. This gene produces a protein called SMN, which is crucial for the survival of the nerve cells involved in muscle function. The severity of SMA is determined by the copy number of a second gene, SMN2, which also produces the SMN protein, although only about 10% of the protein produced is viable.Recent studies suggest that there are additional cellular mechanisms which determine the severity of disease, in addition to copy numbers of SMN2. Despite advanced understanding of the genetics involved in SMA, the cellular mechanisms which cause SMA are not yet completely understood. The team previously observed that the molecular pathways and cellular components which regulate energy in motor neurons are affected in SMA. More importantly, they found that the levels of cellular ATP (cells’ energy store & transport system) was lower in SMA motor neurons.
What are the researchers aiming to do and why?
The team will seek to restore the levels of the energy transport system in motor neurons using a series of molecules to see whether this can ameliorate SMA phenotype.
How will this work benefit patients?
The current clinical trials in SMA which target SMN protein levels are showing great promise. Indeed, one such treatment has just been approved to treat all SMA patients in Europe and the US. Whilst this represents an important milestone in SMA research, it is also clear that these strategies fall significantly short of representing a cure for SMA. Therapies that target other/additional cellular and molecular pathways will likely be required to treat the full range of phenotypes and pathology observed in SMA patients across their life-span. The molecules the team will be using are druggable, which makes them relevant candidates for SMA therapy.