Alim Louis Benabid

Président eHM 2018

Alim Louis Benabid was born on May 2, 1942 at the hospital of Grenoble in La Tronche, France where he would spend most of his training as well as professional life. Since the beginning, he was interested in sciences and followed a double university cursus both in life sciences and in physics. He graduated in medicine and in parallel in physics at the University of Grenoble, and obtained his M.D. Thesis in 1970 and his PhD in physics in 1978. He was appointed Professor of Experimental Medicine in 1978 and then Professor in Biophysics in 1984. He became Head of the Neurosurgery Department at the University Hospital of Grenoble in 1989 until 2004. In parallel, he was Director of INSERM Research Unit U318 « Preclinical Neurosciences » from 1988 to 2007.

Throughout his whole career he was convinced that the practice of medicine in the academic environment (university hospitals) required a simultaneous involvement in scientific research. In this spirit, he went on a sabbatical leave to the Salk Institute in San Diego, California (1979-1980) in the laboratory of Preclinical Neuropharmacology of Floyd Bloom, and in close vicinity to Roger Guillemin’ lab (1977 Nobel laureate in Medicine or Physiology). This one-year spent in this prestigious scientific context had a determining influence on the rest of his career. Being close to remarkable scientists in an impressive technical environment, he became convinced that his neurosurgical discipline and practice could mature to achievements only if intimately inserted into scientific research. Back in Grenoble in 1980, he benefited from the rich local intellectual scientific environment. His contacts facilitated by his physics background at the Grenoble Nuclear Research Center, where he obtained his PhD in physics, gave him the unique opportunity to develop quickly applications of NMR to neurobiology, in MR imaging but mostly in MR spectroscopy. He introduced and developed in his lab other approaches such as molecular biology of brain tumors and electrophysiology for pain. This served as a base for his application to INSERM to create in 1988 the Unit on Preclinical Neurobiology Research. He directed it for 19 years, while simultaneously returning to his neurosurgical activities at the University Hospital and keeping on developing bidirectional bridges between research and clinical practice, from bench to bedside and vice versa. This concept of bidirectional translation in innovation proved very successful leading for instance to Prof Benabid’s invention of Deep Brain Stimulation (DBS) at high frequency.The paradoxical effect of high frequency electrical stimulation provides a wonderful tool to mimic the consequences of lesioning in ablative surgery, but reversibly and in an adaptable manner, making it safe.

The application of this « neurosurgical scalpel », starting in 1987, created a huge momentum in the development of new methods in functional neurosurgery. Since that time, movement disorders such as Parkinson’s disease, essential tremor, dystonia, have been successfully treated by DBS, with extension to several deep brain targets, such as thalamus, pallidum and subthalamic nucleus. The strikingly successful results that he published have permitted the dissemination of the method worldwide and its application to a large number of patients (several hundreds of thousands patients according to recent estimation). The very low morbidity of this approach has allowed to apply it to some indications in mental disorders, as well as feeding disorders , multiple forms of epilepsy, when they are pharmacoresistant and non-resectable, benefit also, to a lesser extent, from the application of DBS.

 

Nevertheless the mechanism of action of DBS at high frequency is still poorly understood and has triggered very active experimental, theoretical, or technological research in dozens of labs throughout the world.

However, the beneficial effects of the DBS method produced, similarly to what is obtained using the best medical treatment currently available, are still strictly symptomatic, contemporaneous to the application of electrical stimulation, but stops as soon as stimulation is discontinued. Moreover, the neurodegeneration has progressed and the basic pathogeny of these diseases is not altered by the electrical stimulation even for periods as long as 29 years now in some patients.

Therefore there is an urgent need to develop neuroprotective approaches. To achieve this, for the past five years, in cooperation with the group of John Mitrofanis in Sydney, Prof Benabid has taken advantage of the cell healing properties of the near infrared lights (670 and 810 nm) illumination of suffering cells. The alleged mechanism of action is the absorption by photoacceptors such as cytochrome C oxidase of the photon energy which is transferred to the electron transport chain leading to an improved respiratory process into the cell and the mitochondria, leading to an increased production of ATP. They have developed a totally new method, evaluated in mice, rats, and primates using an implanted laser sources connected to fibers introduced endoventricularly in the close vicinity of the two substantia nigra compacta. Prof. Benabid and colleagues hope to be able to start in the very beginning of 2018.

Another major aspect of Prof. Benabid’s current activity is the so-called Brain Computer Interface in Tetraplegics. In the same spirit of having multi-disciplinary and multi-institutional approaches of medical therapeutic problems, he has started the project to provide to full four-limb tetraplegic patients the possibility of a better mobility through robotized motorized four-limb embedding exoskeleton. This exoskeleton is meant to be piloted by the patient’s brain activity, continuously recorded through fully implantable wireless electro corticographic recorders implanted bilaterally against the dura in the sensory motor area previously recognized and localized using functional imaging such as functional MRI as well as magneto-encephalography. This ECOG activity has to be transmitted to a station held in the back of the exoskeleton, where it is analyzed using an original software developed in Prof. Benabid’s lab by a team of mathematicians while the robot has been developed by a team of engineers belonging to a specialized department of the CEA  (Atomic Energy Commission). That team has developed from scratch the complete exoskeleton which will be used in a clinical trial. The clinical trial has been very recently accepted by the regulatory bodies and the first patient has been recruited and implanted.

This is a rather brief description of Prof. Benabid’s various activities during his career. They are globally dominated by his double background in medicine and physics and his restless efforts to apply as often as possible the productive capacity of succesful transfers from bench to bedside.

Prof. Benabid’s recent achievements have been made possible to a large extent by the creation, at the time of his retirement 10 years ago, of a Biomedical Research Center called Clinatec (6400 m²) funded by the French government and a strong mecenial support, and in particular the Edmond J Safra Philanthropic Foundation. Prof. Benabid is currently the Chairman of Clinatec in Grenoble.

Prof. Benabid has received all along his career many international prizes and awards. More recently, he has been the recipient of the 2013 Robert A. Pritzker Prize for leadership in Parkinson’s disease research, the 2014 Lasker~DeBakey Clinical Medical Research Award (« the Lasker Prize ») for « paving the way for the clinical use of deep brain stimulation to treat Parkinson’s disease » and the 2015 Breakthrough Prize in Life Sciences. During the award ceremony of the Breakthrough Prize in San Francisco,  Mark Zuckerberg said. “This year’s Breakthrough Prize winners have made discoveries that will help cure disease and move the world forward. They deserve to be recognized as heroes. »

An exceirpt of Prof. Benabid’s Lasker award’s acceptation speach describes well the past 40 years of his career: « I would say that my life has been a science fiction novel, my story being based on the patient’s problems and expectations, the use of increasingly sophisticated tools in the battles, the thrill of facing challenges, and the delight of solving them, with sometimes happy ends for the patients, and sometimes not. »

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