Trevor Kilpatrick, Director, Melbourne Neuroscience Institute, University of Melbourne, Melbourne, VIC
Multiple sclerosis (MS) is traditionally considered a T cell mediated disease in which auto-reactivity is induced by an unknown antigen producing inflammatory demyelination within the central nervous system (CNS). This perspective has resulted in the development of a series of immune therapies that modulate the adaptive immune system to treat early stage, relapsing remitting MS. However, despite the advent and utilization of these therapies, many patients still develop progressive MS, characterized by impaired remyelination and ongoing neurodegeneration. Current evidence points to dysregulation of the innate immune system as a major determinant of the degree of ongoing damage and the capacity for myelin repair. Therapeutic approaches targeting the innate immune system therefore hold great promise for inhibiting the progressive, neurodegenerative phase of MS. The TAMs (Tyro3, Axl and Mertk) represent a family of tyrosine kinase receptors expressed by discrete cell types. Mertk and Axl are involved in the regulation of innate immune responses, including antigen presentation, increased production of anti-inflammatory cytokines, and potentiation of the phagocytosis of apoptotic cells and myelin debris. In addition, Mertk is both a susceptibility and severity gene for MS. In experimental models of MS, loss of Gas6, an agonist for all three TAM receptors, leads to increased disease and delays repair. Unlike Axl and Mertk, Tyro3 is predominantly expressed by oligodendrocytes, the myelinating cell of the CNS. Tyro3 mediates the pro-myelinating effect of Gas6 and Tyro3 deficiency abrogates remyelination. Collectively, these findings have encouraged us to develop strategies aimed at potentiating TAM receptor activity for therapeutic benefit in MS.
TTrevor Kilpatrick is a Professor of Neurology and Director of the Melbourne Neuroscience Institute at The University of Melbourne; he is the leader of the MS Division at the Florey Institute of Neuroscience and Mental Health and is a neurologist and Head of the MS Unit at the Royal Melbourne Hospital. Professor Kilpatrick graduated with a Bachelor of Medicine, Bachelor of Surgery from the University of Melbourne in 1982 and then went on to specialise in neurology. He undertook graduate studies at The University of Melbourne and gained a Doctor of Philosophy in 1993. Appointments at The Salk Institute for Biological Studies (La Jolla, USA), Institute of Neurology (London, UK) and The National Hospital and Moorfields Eye Hospital (London, UK) followed. He returned to Melbourne as the Viertel Senior Medical Research Fellow at the Walter & Eliza Hall Institute for Medical Research and as the Head of the Melbourne Multiple Sclerosis Research Unit at the Royal Melbourne Hospital. Professor Kilpatrick has been the recipient of the Sunderland Award (1994), AMRAD Postdoctoral Award (1995), inaugural Leonard Cox Award (2000), Bethlehem Griffiths Research Foundation Award for Medical Research (2004), the Australian Museum’s Jamie Callachor Eureka Prize for Medical Research (2008), the Stephen C. Reingold Research Award by the US MS National Multiple Sclerosis Society (2010), the Bethlehem Griffiths Research Foundation Medal for outstanding leadership in medical research (2013), and most recently, he was elected as a Fellow of the Australian Academy of Health and Medical Sciences (2016).Professor Kilpatrick has published widely including publications in Nature, Nature genetics and Nature Medicine. His research interests include the neurobiology of multiple sclerosis, neural precursor cell biology and the study of genetic and environmental factors that contribute to MS as well as the translation of basic research discoveries to the clinic.