DrGonzalo Perez-Siles

The lack of effective treatments for IPNs is in part due to the absence of relevant human neuronal models that can be utilised for bridging the currently existing gap between in vitro studies and clinical application. We are currently growing motor neurons and peripheral nerves from induced pluripotent stem cells (iPSC) derived from a variety of IPN patients which disease causing mutations had been previously identified in our gene discovery program.

Among the iPSC lines we have stablished at the Northcott Laboratory I am particularly interested in identifying pathomechanisms leading to degeneration of axons in motor neurons derived from 2 subtypes of IPN patients:

- X-linked Charcot Marie Tooth type 6 (CMTX6), caused by mutations in the pyruvate dehydrogenase kinase 3 gene (PDK3), represents a unique opportunity to perform screening of molecules that can revert a known pathogenic signature in patient derived motor neurons. By using motor neurons derived from CMTX6 patients we are currently in the position to assist in the development of future treatment strategies for these intractable diseases.

- X-linked distal hereditary motor neuropathy (dHMNX), caused by mutations in the ATP7A gene, a P-type ATPase essential for cellular copper (Cu) transport and homeostasis. dHMNX is a non-fatal form of motor neuron disease (MND). Understanding how Cu dysregulation leads to axonal degeneration of motor neurons will facilitate development of Cu based treatment therapies.