Commencing January 2023, Dr Steven Petratos and Professor Paul Stupple, Monash University, were awarded a 2-year Trish Translational Research Project Grant titled, “Development of Small Molecules to Promote Remyelination in Multiple Sclerosis”.
Animal models of multiple sclerosis (MS) are important to understand how brain cells die during disease and how we can target specific molecules safely to stop this. The aim of Professor Stupple’s and Dr Petratos’ research is to first understand how specific molecules, when decreased, limit the survival of cells (known as ‘oligodendrocytes’) that wrap a protective coating around nerve fibres (known as ‘myelin’). Such a change can cause damage to the brain but excitingly there is a class of drugs that is now moving into clinical trials that may be able to stop this damage to the oligodendrocytes and myelin to limit the progressive neurological decline that can occur in MS over time. Moreover, these drugs may offer the added benefit of enhancing the generation of new oligodendrocytes from their immature cells (‘stem cells’), thereby facilitating the making of new myelin in areas of the brain where the disease has caused myelin loss (‘demyelination’).
Dr Petratos’ and Professor Stupple’s group has uncovered that in the brains of people living with progressive MS, there exists a dysregulation of specific proteins that are central to the metabolism (energy) of oligodendrocytes making them vulnerable to cell death and thereby causing brain damage. Importantly, they have discovered that a new class of medicines, known as small molecules, can stop the death of these brain cells by protecting their metabolism. This outcome has major implications in the protection of these myelin forming cells in the brain and can limit further damage imposed by the immune attack as seen in the progression of MS. They are now investigating whether newly synthesised small molecules that may have superior efficacy in oligodendrocyte culture models can lead to new preclinical animal trials in the MS-like model of disease. These outcomes will allow the team to fast-track the development of the best performed drug-like molecules toward future clinical trials when they are deemed safe for human use to stop and reverse the damage to the brain that occurs in progressive MS. Specific details are confidential for now.
Dr Petratos first received funding from the Trish MS Research Foundation in our inaugural round of funding in 2002. The Foundation has supported much of his great work over the past 25 years. Dr Petratos was the only Australian researcher to receive funding from the International Progressive MS Alliance in their inaugural round of funding. Our team of volunteers is honoured to contribute to this exciting work.