Funded Research Projects


Cellular basis of motor circuit dysfunction induced by SMN deficiency

Principal investigator(s):
Dr. George Mentis
Columbia University (USA)
Start Year:
2 years
SMA Europe
Call number:


Dr. George Mentis

Q. Is the death of the motor neurones in SMA due to changes in the cell itself or is it due to a dysfunction in the network in which they belong?

 A. The project is ongoing Motor neurones participate in the wiring system or motor circuit, which sends electrical impulses from the brain to the muscles, controlling how they contract and relax. A hallmark of SMA is the death of these motor neurones due to low levels of a protein called SMN. However, in a mouse model of SMA, dysfunction in motor circuits as a whole is one of the earliest manifestations of the disease, as it precedes neuronal death. George Mentis and his colleague Livio Pellizzoni propose to gain insight into this dysfunction by looking at the communication between the different neurons that make up this circuit and its role in motor neurones death. The investigators will do this by first developing and characterising a stem cell-based motor circuit and secondly, using this new motor circuit, by looking at the changes induced by SMN deficiency in both motor neurones and the neurons they network with. This is important as, to date, death and dysfunction of motor neurones in SMA have long been considered solely as a cell-autonomous problem. This study should bring new insights into disease mechanisms and allow the development of novel therapeutic approaches for SMA.