Defining the role of novel molecules in the pathogenesis of MS (Ahmed, Logan, Fulton)
The development of a new treatment that promotes repair of axons and their associated myelin sheath would revolutionise the outlook for patients and their carer's. Currently, there is no treatment to reverse the axonal damage that occurs in MS. However, we have identified several molecules that might be useful in promoting myelin repair and regeneration in the damage CNS. This is a huge unmet need, particularly for patients with progressive disease (both primary and secondary progressive MS) in which none of the available agents have been shown to be effective.
We will test the hypothesis that antagonism of several of these molecules that are highly upregulated in oligodendrocytes precursor cells will promote their differentiation into myelinating oligodendrocytes and thus enhance myelin repair. Our preliminary experiments also demonstrate that these molecules are present in reactive astrocytes, macrophages/microglia and in MS lesions. Understanding how these molecules are dysregulated in MS may define new molecules for therapeutic utility in the fight against MS.
Neuroprotection in optic neuritis (Ahmed)
Around 10-30% of individuals affected by MS have a clinical presentation that manifests with inflammation of the optic nerve (optic neuritis) followed by the development of relapsing-remitting MS. Optic neuritis leads to loss of vision due to conduction block, demyelination and subsequent loss of retinal ganglion cells in the retina. The underlying immunological basis for different clinical forms of MS and its association to optic neuritis is not well defined. However, MRI studies have shown that people with this condition often have brain lesions and the involvement of the optic nerve. Optic neuritis can result is visual impairment in a proportion of affected individuals and results in retinal nerve loss.
Working with colleagues at the Blizzard Neuroscience Centre, Queen Mary, University of London, UK, we have shown that caspase-2, an orchestrator of apoptosis, is activated in retinal ganglion cells during the development of optic neuritis and its suppression with a nuclease stable siRNA prevents retinal ganglion cell apoptosis and preserves retinal fibre layer thickness. We are currently analysing the utility of these therapeutic molecules in treating individuals affected with this medical condition.