In Context

504 www.thelancet.com/neurology Vol 10 June 2011

Jeff rey Cohen likes complicated problems, and that is precisely why he chose to work on multiple sclerosis (MS). The cause is unknown, the disease involves two of the body’s most complex systems, and no treatments are completely eff ective. He is thus very much at home as Director of Experimental Therapeutics at the Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research (Cleveland, OH, USA).

Cohen had been interested in the brain since before medical school. His father was a trained psychiatrist who worked as a research scientist. “That’s possibly where I got my interest in neurology from”, says Cohen. But at medical school (University of Chicago, Chicago, IL, USA) he also developed a deep interest in immunology. Why? “Because, second only to the nervous system, it is probably the most complicated system in the body”, he says, true to form.

Cohen was able to marry these two interests when, in his last year of medical school, he spent 6 months in the research laboratory of Jack Antel: “I think it was a coalescence of my interests in immunology and neurology together with my opportunity to work with a great mentor that solidifi ed my interest [in MS].”

After medical school came an internship, residency, and fellowship at the University of Pennsylvania (Philadelphia, PA, USA), and further opportunities to pursue research, fi rst with Robert Lisak and then with Mark Greene. “I had been undecided about whether to do research or clinical medicine”, says Cohen, “and I ended up doing both.” Indeed, he set up his own basic research laboratory for several years studying, among other things, lymphocyte traffi cking in MS.

“In the early 1990s I then became interested in applying some of those more basic insights to developing new therapies”, says Cohen, “so my activity started to switch from basic research into clinical trials.” Around the same time, the Mellen Center was looking to develop a clinical trials programme. The fi t seemed good and the move was made.

“I recruited Jeff to the Mellen Center”, says Richard Rudick, the Center’s director. “It quickly became apparent that he had the capability to totally immerse himself in the enterprise in which he was working—both scientifi cally (in this case the clinical sciences related to clinical trials) and clinically (diagnosis and management of MS).”

Since joining the Center in 1994, Cohen has designed, organised, and run countless MS trials, and has consequently had a role in testing most of the agents investigated in MS. He was involved with the fi rst phase 3 trial of glatiramer acetate in the USA, which ultimately led to its approval. He also designed and managed a

large multicentre trial—the scale of which normally only pharmaceutical companies would consider—to investigate interferon beta-1a in combination with other drugs (the Avonex Combination Trial). Subsequently, he helped design and run one of the phase 3 trials of the now-approved drug, fi ngolimod. “He has an energy and persistence for taking on large, extended, even audacious trials”, says Robert Fox, Medical Director at the Mellen Center. Maybe that is down to Cohen’s love of a complicated task.

The fi ngolimod trials were of particular interest to Cohen: the drug is the fi rst oral treatment approved for MS, and the method of action, regulation of lymphocyte traffi cking, is novel compared with other immunomodulatory therapies. “My previous lab interest has now come full circle”, he says, “which is very gratifying.” The results of a new fi ngolimod extension study are published in this issue of The Lancet Neurology.

Although fi ngolimod and other approved drugs for MS are eff ective in the treatment of relapsing-remitting MS, none has been shown to work for the more severe form of the disease: progressive MS. “Our available therapies prevent the damage, but don’t repair the damage”, Cohen explains. A new phase 1 trial that Cohen has recently embarked on, however, might be set to change that. The trial is the fi rst grant-funded formal trial of mesenchymal stem cells for MS, Cohen explains proudly. Although its preliminary goal is to establish safety of the treatment, Cohen is reservedly excited: “The main incentive for testing stem cells is for their reparative properties, which we think will be very important for progressive MS.”

In addition to designing and executing many trials, Cohen has established “the best existing clinical research training programme in the MS fi eld”, according to Rudick. Cohen says he developed the programme because “many of the people involved in the early MS clinical trials were people like me…we learned to do clinical trials on the fl y”. He adds: “It became clear that if we wanted to train the next generation of MS clinical trialists, they needed more formal training in trial methods, statistics, epidemiology, and trial conduct.”

It is hard to imagine someone better equipped to train the upcoming MS clinical researchers than Cohen. “His range of knowledge with MS trials spans from basic science…all the way through to phase 1 to 4 trials, and to the clinical relevance of the results…It is really tremendous”, says Fox. “He was my mentor for 2 years, when I was a fellow, and indeed continues to be a mentor of sorts. You know, when it comes to good mentors, you just don’t let them go.”

Ruth Williams

Profi leJeff rey Cohen: covering clinical trials of MS from all angles

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