|Sir Marc Feldmann|
2 December 1944 |
|Institutions||Kennedy Institute of Rheumatology, University of Oxford|
|Alma mater||University of Melbourne
Walter and Eliza Hall Institute of Medical Research
|Known for||discovery of anti-TNF therapy as an effective treatment for rheumatoid arthritis and other autoimmune diseases|
|Notable awards||Crafoord Prize (2000)
Albert Lasker Award for Clinical Medical Research (2003)
EPO European Inventor of the Year Award (2007)
Dr. Paul Janssen Award for Biomedical Research (2008)
Ernst Schering Prize (2010)
Feldmann was born 2 December 1944 in Lvov, Poland near the Russian border to a Jewish family who managed to get to France immediately postwar (i). He emigrated from France to Australia at age eight. After graduating with an MBBS degree from the University of Melbourne in 1967, he earned a Ph.D. in Immunology at the Walter and Eliza Hall Institute of Medical Research in 1972 with Sir Gustav Nossal (i).
He moved to London in the 1970s, working first with Professor Avrion Mitchison at the Imperial Cancer Research Fund's Tumour Immunology Unit, then in 1985 moved to the Charing Cross Sunley Research Centre and the Kennedy Institute of Rheumatology which joined with the Faculty of Medicine at Imperial College in 2000 and in August 2011 the Kennedy Institite of Rheumatology transferred to the University of Oxford.
In the 1980s he published a new hypothesis for the mechanism of induction of autoimmune diseases, highlighting the role of cytokines (ii). Cytokines are potent signalling proteins, local hormones, which drive important processes like inflammation, immunity and cell growth. This model was validated in experiments with thyroid disease tissue. From 1984 he collaborated with Ravinder N. Maini at the Kennedy Institute of Rheumatology to study disease mechanism in rheumatoid arthritis, a much more clinically important autoimmune disease, affecting 1% of the population.
In autoimmune diseases, the immune system attacks and damages the body, leading to disease of various organs, for example joints in rheumatoid arthritis. Feldmann's group demonstrated that diseased joints have far more pro-inflammatory cytokines than normal, and identified one of these, Tumour Necrosis Factor Alpha, abbreviated TNFα as the key (iii).
Blocking TNFα reduced levels of the other pro-inflammatory cytokines in test-tube models of arthritis (iv), and this provided the rationale for testing TNF blockade in rheumatoid arthritis patients which had failed all existing treatment.
The first of a series of successful clinical trials was performed in 1992, at Charing Cross Hospital, using an antibody, infliximab from Centocor, a biotech now part of Johnson and Johnson.
The success led to other companies joining the race to market, and by 1998 (v), etanercept (Enbrel) (vi) was approved for treatment in the US, and by 1999, infliximab (Remicade) was also approved. Now there are 5 approved anti-TNF drugs, and they are extensively used, with more than 2 million successfully treated patients.
Since then, TNFα inhibitors have become the therapy of choice for stopping the inflammatory and tissue-destructive pathways of rheumatoid arthritis and other autoimmune diseases including Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriasis and psoriatic arthritis (vii).
(i) Feldmann, M. (2009) Translating molecular insights in autoimmunity into effective therapy. Ann. Rev. Immunol. 27: 1-27.
(ii) Bottazzo, G.F., Pujol-Borrell, R., Hanafusa, T. and Feldmann, M. (1983) Hypothesis: Role of aberrant HLA-DR expression and antigen presentation in the induction of endocrine autoimmunity. Lancet ii: 1115-1119.
(iii) Feldmann, M., Brennan, F.M. and Maini, R.N. (1996) Role of cytokines in rheumatoid arthritis. Ann Rev. Immunol. 14: 397-440.
(iv) Brennan, F.M., Chantry, D., Jackson, A., Maini, R.N. and Feldmann, M. (1989) Inhibitory effect of TNF-alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet ii: 244-247.
(v) Elliott, M.J., Maini, R.N., Feldmann, M., Long-Fox, A., Charles, P., Katsikis, P., Brennan, F.M., Walker, J., Bijl, H., Ghrayeb, J. and Woody, J. (1993) Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to TNF-alpha. Arth. Rheum 36: 1681-90.
(vi) Elliott, M.J., Maini, R.N., Feldmann, M., Kalden, J.R., Antoni, C., Smolen, J.S., Leeb, B., Breedveld, F.C., Macfarlane, J.D., Bijl, H. and Woody, J.N. (1994) Randomised double blind comparison of a chimaeric monoclonal antibody to tumour necrosis factor-alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 344: 1105-1110.
(vii) Feldmann, M. and Maini, R.N. (2001) Anti-TNF-alpha therapy of rheumatoid arthritis: What have we learned? Annual Review Immunology 19: 163-196.
Prizes and fellowships
Marc Feldmann and Ravinder Maini shared many awards for their discovery. In 2000, Feldmann and Maini were awarded the Crafoord Prize "for identification of TNF blockade as an effective therapeutic principle in rheumatoid arthritis". In 2003, the two were awarded the Albert Lasker Award for Clinical Medical Research for discovery of anti-TNF therapy as an effective treatment for rheumatoid arthritis and other autoimmune diseases. In 2004, the Cameron Prize for Therapeutics of University of Edinburgh. In 2007, Feldmann was awarded The European Patent Offices "European Inventor of the Year" in the Lifetime Achievement Category. In 2008 he was awarded the Dr. Paul Janssen Award for Biomedical Research together with Maini. He was awarded the John Curtin Medal of the Australian National University in 2007. Feldmann and Maini were awarded the Ernst Schering Prize in Germany in 2010.
He is Fellow of the Royal College of Physicians and of the Royal College of Pathologists. He was elected a Fellow of several national Academies, the Academy of Medical Sciences, the Royal Society of London and is a Corresponding Member of Australian Academy of Science,</ref> and a Foreign Member of the National Academy of Sciences, USA. He was knighted in the 2010 Queen's Birthday Honours.
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- "Professors Marc Feldmann and Sir Ravinder Maini Named Winners of the 2008 Dr. Paul Janssen Award for Biomedical Research". Johnson & Johnson Pharmaceutical Services. Retrieved 23 November 2008.
- The London Gazette: . 12 June 2010.
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