In Context

30 www.thelancet.com/neurology Vol 13 January 2014

Satoshi Kuwabara is a workaholic. When The Lancet Neurology caught up with him in November, it was Culture Day in his native Japan; but, while most of the rest of the country was enjoying a long weekend, Kuwabara was in his offi ce at the Department of Neurology in Chiba University. He’s seldom anywhere else. “Japanese doctors, particularly professors, have too many things to do: research, education, clinical and hospital management”, he explains “I rarely have a holiday.” But the unsociable hours have brought their rewards. His compulsion for research and impatience for answers “has driven an extraordinary and highly productive research career”, says Matthew Kiernan, Bushell Chair of Neurology at the Brain and Mind Research Institute at the University of Sydney in Australia.

It was in Sydney in 1999, under the guidance of the pioneering neurophysiologist David Burke, that Kuwabara says he got his fi rst grounding in research. “Before I went to Sydney I actually didn’t know what medical research was”, he recalls. He went into medicine with the idea of following his father into general practice, before settling on neurology as a graduate medical student at Chiba, but it wasn’t until that year spent in Australia that he entertained notions of being a clinician-scientist. “My life changed in Sydney”, he says. Burke was, and still is, a trailblazer in the area of ion channel physiology and, after spending a year studying hyperexcitability in Burke’s laboratory, Kuwabara returned to Chiba to set up his own research programme, focusing on developing new ion channel modulators to treat neurological diseases.

Kuwabara’s decision to nail his colours to the mast of neurophysiological research came at a time when most of his colleagues were being seduced by molecular neurology, and although he is keen to emphasise the importance of a multidisciplinary approach to clinical research, he is still evangelical about the benefi ts of a neurophysio-logical perspective. “I favour neurophysiological assess-ment because it gives us real-time information on nerve and brain function”, he explains. “When I examine patients I can see the fi ndings in real time, so that’s a big diff erence from the molecular biological approach.”

His approach paid dividends early on, with the discovery that ion channel irregularities linked to motor axons were implicated in several diseases. “He discovered a novel fi nding that IgG anti-GM1 antibodies are associated with reversible conduction failure as well as axonal degeneration in Guillain-Barré syndrome [GBS]”, explains Nobuhiro Yuki, research professor at the Department of Medicine of the National University of Singapore and coauthor with Kuwabara of a Review on the subject

of axonal GBS. Axonal GBS is an immune-mediated polyneuropathy that causes muscular paralysis; as a result of Kuwabara’s work, “the condition is now being increasingly recognised in non-Asian populations; an eff ort that has not been without strenuous debates with non-believers, particularly his European colleagues”, explains Kiernan.

His work on the eff ects of ion currents has led him on a quest to develop new treatments for a host of other neurological disorders. “Every day I’m thinking about new treatment options”, he says, and with what Kiernan calls “a vision for building clinical networks at a local level in Chiba, through to national and international levels”, he’s been able to put several new treatments to the test. His work on the rare disease POEMS syndrome is a case in point. Also known as Crow–Fukase syndrome or Takatsuki disease, POEMS syndrome is a rare multi-system disorder associated with plasma-cell proliferation, in which plasma cells secrete excess cytokines and cause multi-organ failure. “Before 2000, the mean survival of a patient with POEMS syndrome was only 3 years”, Kuwabara explains. His group was able to put together a clinical network and start a multicentre trial of intensive treatment with high-dose chemotherapy and peripheral stem-cell transplantation from the mid-2000s, with the result that mean survival is now more than 12 years for the disease.

Having developed a similar network for amyotrophic lateral sclerosis in Japan, Kuwabara’s team is running a trial to investigate the eff ects of sodium-channel blockers on the pathology of that disease, and plenty more developments are sure to come from Kuwabara’s carefully crafted multidisciplinary research group in the future. “His group in Chiba is now a world force”, says Kiernan, and his infl uence on young students extends well beyond his country’s borders. “Satoshi has helped to support the development of neurologists and scientists from many labs around the world. He will never turn down a request to help”, Kiernan notes.

How long he can sustain his frenetic pace of life is another matter. Living in Chiba—a more relaxed suburban city than the heaving metropolis of Tokyo 30 miles to the northwest—helps with his blood pressure, he says, but it turns out that Kuwabara really unwinds by indulging a slightly unlikely passion for 70s rock. “Led Zeppelin, Deep Purple, they’re my favourites”, he says, although he admits to throwing some jazz into the mix when he really needs to relax. We can only hope it does the trick.

David Holmes

Profi leSatoshi Kuwabara: work hard, rock hard