Professor Dr Alastair Compston

Research Priorities: Multiple sclerosis, pathogenesis and novel therapies, genetics
Alastair Compston is a British neurologist. Now retired, he has been researching the aetiology, disease mechanisms and therapeutics of multiple sclerosis (MS) since the mid-1970s. He is acknowledged as a leader in this research field over several decades. With his many collaborators in Cambridge and internationally, he has been associated with the identification of genetic risk factors for MS, he developed a novel therapy approach with drug development through to licencing of Lemtrada©, and he has advanced concepts on the complex pathogenesis and evolution of disease progression.
Multiple sclerosis is an inflammatory disease of the central nervous system. It is established that the body’s own immunological defence system intermittently attacks the protective membranes (myelin sheath) of nerve fibres, and the underlying axons, in the brain and spinal cord. This results in episodes of neurological dysfunction manifesting, for example, as impaired vision, loss of sensation and weakness.
Starting with his co-demonstration of the link to HLA-DR15 (1976), Alastair Compston and his many colleagues have systematically shown that multiple sclerosis develops against the background of genetic susceptibility in which many risk variants, each individually exerting a small effect, underly the predisposition to disease. In related work, he has studied the cellular neurobiology of glia, especially myelin-forming cells in the central nervous system, as the basis for understanding the possibilities for enhancing endogenous and exogenous repair.
With others, Alastair Compston developed a novel therapy approach in which the attacking immune cells are depleted using biological medicines (monoclonal antibodies) leaving a sufficient number to deflect coincidental infections but too few to maintain disease activity in the nervous system. Later the repertoire is reconstituted providing significant longer term disease protection but not without adverse effects, especially secondary autoimmunity affecting other organs. The antibody Alemtuzumab (Campath-1H) is now marketed as Lemtrada©. Alastair Compston has shown that it is possible to slow down activity of the disease in the early stages of multiple sclerosis in most patients, and thereby to delay or even prevent subsequent progression. Alemtuzumab is now an established means of treatment amongst a growing number of other therapies for multiple sclerosis, each varying in their risk-benefit ratios.