Multiple Sclerosis and Neuroimmunology Group

Kinase inhibitors

We have identified a key genetic and molecular marker for personal risk stratification in MS. The marker is MERTK, which is expressed on some white blood cells, including those which could cause damage to the CNS.

We are investigating whether inhibition of MERTK activity on these cells in the blood, before they target the CNS, could prevent MS activity, especially in people expressing high levels of MERTK on these cells.

We have also identified that people treated with the medication, natalizumab (which benefits MS by reducing white blood cell entry into the CNS) who carry a high expressing variant of the MERTK gene exhibit more breakthrough activity, risking poor long-term outcome.

We are currently assessing how variations in MERTK expression influence the response of MS to other currently available treatments and exploring if white blood cells that drive MS activity can be inhibited by modulating MERTK expression for therapeutic benefit. The potential outcomes include a) establishment of MERTK genotyping as a bone fide component of MS medication selection and b) validation of white blood cell MERTK as a target for MERTK-selective kinase inhibitors in a focused drug discovery program.

Tolerogenic therapy for multiple sclerosis

We aim to develop a new way to treat MS based on using patients’ own blood immune cells. These cells are treated with anti-inflammatory signals in the laboratory and then re-administered to the patient, where they selectively target and dampen down the disease-causing immune cells that promote inflammation and cause nerve cell damage in MS. This approach has advantages over existing therapies as it targets key initiating events in MS, avoids the risks of suppressing the immune system broadly such as infections, and could treat both relapsing and progressive disease stages.

We have already developed techniques to grow these immune cells from patient blood samples and defined culture conditions that can modify their behaviour to assume protective/anti-inflammatory rather than disease-inducing/pro-inflammatory characteristics. We have identified relevant proteins involved in MS that enable selective targeting of the disease-causing immune cells.

Our current work focuses on identifying patient populations who may be suitable candidates for this therapy based on genetic risk factors for MS, testing this approach in a mouse model of MS and developing cell-based products and protocols that meet GMP criteria.