Targeting Progressive MS

In January 2020 Dr Steven Petratos was awarded a 3-year Trish Translational Research Project Grant titled, “Development of a small molecule to promote neuroprotection and repair in progressive multiple sclerosis”. Dr Petratos and his team are working on developing a new drug for progressive multiple sclerosis and, despite some barriers with lockdowns in Melbourne and National border restrictions limiting Dr Petratos’ collaborative research engagement with Associate Professor Kaylene Young who is a Chief Investigator on the current grant, excellent progress has been achieved.

The first Aim of Dr Petratos and his team was to trial the MCT8-independent thyroid hormone analogue, DITPA, as a potential therapeutic agent in neuroinflammatory-mediated models of demyelination to promote neuroprotection.

Animal models of multiple sclerosis (MS) are vitally important for the understanding of how the
cells in the brain undergo change during disease progression and how we can target specific
molecules safely to stop the progression. The main goal of Dr Petratos’ research proposal is to first
understand how a specific group of 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 may be able to
stop this damage to the oligodendrocytes and myelin with the added benefit of stimulating repair
to the damaged brain, by enhancing the generation of new oligodendrocytes from their immature
cells (‘stem cells’) and making new myelin. If this project is successful, a new series of drugs will be
available for development targeting progressive MS.

The data generated demonstrates the therapeutic potential of DITPA to promote the protection of oligodendrocytes in the context of neuroinflammatory challenge and may indeed potentiate the enhancement of remyelination through the activation of oligodendroglial precursor cells (OPCs).
These experiments may well identify how OPCs can be salvaged and stimulate differentiation during MS, allowing for the repair of demyelinated lesions ultimately, potentiating neurological recovery of patients living with MS.

A new collaborative project with Medicinal Chemists at the Monash Institute Pharmaceutical Science (MIPS) has been engaged with funding through the Therapeutic Innovation Australia pipeline accelerator grant and new commercial contract that has just recently been engaged. The lead MIPS researcher on this new project is Professor Jonathan Baell.

A new commercial agreement that started in April 2021 related at bringing the current small molecule to clinical trial in the near future will allow Dr Petratos to recruit two full time Postdoctoral Fellows to ensure successful translation of the current research. Dr Petratos and his team have a Manuscript in preparation.