Mechanisms of Myelin Repair

The pathophysiology of Multiple Sclerosis (MS) is complex and as a consequence it is often described as a disease of two phases; 

1) the initial ‘autoimmune’ phase in which an unknown trigger causes the immune system to sporadically attack and destroy myelin of the central nervous system (CNS) and, 

2) the secondary progressive ‘neurodegenerative’ stage where demyelinated neurons begin to die in large numbers and are not replaced. 

At present, there are no drugs on the market that are primarily neuroprotective, and this presents a significant problem for neurologists who treat MS patients in later stages of the disease. New medications that prevent neurodegeneration, the root cause of the irreversible and debilitating motor and cognitive disabilities associated with secondary progressive MS, would extend and greatly enhance the quality of life of people living with MS.

Our research group adopts an interdisciplinary approach to investigating the physiological mechanisms which are disrupted in both early and late stages of MS. We are currently characterising a novel therapeutic that could halt or reverse neuronal and oligodendrocyte cell death in neuroinflammatory diseases, like MS. We have promising pre-clinical data showing that the peptide, GsMTx4, protects neurons and promotes axonal myelination in the brain.

GsMTx4 (also known as AT-300) is a non-toxic component of tarantula venom and blocks stretch-activated calcium (Ca2+) channels (SACs), thus preventing Ca2+ overload in cells. Our data suggests that blocking SACs in the CNS prevents demyelination and enhances developmental myelination. We are currently investigating Piezo1 as a novel drug target for neuroprotection in primary and secondary progressive MS and will further characterise the therapeutic effects of the peptide, GsMTx4. 

Results from this project will provide a greater understanding of the therapeutic potential of targeting mechanosensitive calcium channels expressed by CNS neurons and glial cell types. Our long-term goal is to develop novel therapeutics that can prevent neurodegeneration and promote re-myelination of axons in later stages of Multiple Sclerosis, as well as other neuroinflammatory and neurodegenerative diseases.