Targeting neuroprotection in progressive multiple sclerosis

A key driver of progression is neurodegeneration, the damage and loss of nerve cells. This close link between neurodegeneration and disease progression underscores its importance as a treatment target. Despite available treatments for multiple sclerosis (MS), protecting the nerves, or “neuroprotection”, remains a significant unmet need, particularly for those living with progressive MS.

In this project, Dr James Hilton and his team are studying a group of compounds called bis-thiosemicarbazones (BTSCs) for their ability to protect the nerves. These compounds have already shown promise in several neurological diseases, including motor neurone disease and Parkinson’s disease, especially through a compound called copper-atsm, or Cu(atsm). They have also shown that Cu(atsm) improves outcomes in models of MS by boosting growth of the protective myelin coating around nerves, reducing lesion size, and supporting nerve repair. It also corrected several copper‑related problems seen in progressive MS.

There is additional evidence that Cu(atsm) may protect nerves by stopping a type of cell death called ferroptosis, driven by iron. Since ferroptosis may play a role in MS, this could be another useful pathway for treatment. Although Cu(atsm) seems to act on both copper imbalance and ferroptosis, it is still unknown how much each of these actions contributes to neuroprotection.

To explore this, Dr Hilton will develop and test new BTSC compounds in cell culture. These compounds will be selected based on their ability to target copper imbalance, ferroptosis, or both. The most promising compounds from each group will then be tested in a model of MS to assess their therapeutic benefit and confirm they act on the intended biological pathways while providing neuroprotection. By understanding how these mechanisms contribute to MS, Dr Hilton and his team aim to discover new and more effective BTSC compounds that could eventually move into clinical testing.