Tuesday, 27 August 2013

Interview with Professor Michel Revel - Inventor of Rebif (interferon-beta), Chief Scientist at Kadimastem

Professor Revel began his career in a laboratory associated with the Pasteur Institute in Paris, where he discovered the initiation factors of protein synthesis. This discovery opened up a field of research on the mechanisms controlling the translation of genetic information.

Prof Revel’s scientific path continued at the Weizmann Institute, where he conducted extensive research on the mechanisms of action and the isolation of the human Interferon-beta gene. These studies have led to the biotechnological development of recombinant Interferon-beta (Rebif) at Interpharm.  Rebif is today the lead product of Merck Serono, a $2.4 billion-a-year commercial drug, widely used to treat multiple sclerosis (MS), a disease that destroys the myelin coating of nerves in the brain.

Revel also discovered the human gene for the cytokine Interleukin-6, and elucidated its activity in protecting nerve functions and the nerve myelin coating in neuropathies. In recent years, Revel's laboratory focused on human embryonic stem cells (hESC) and succeeded to produce from them mature nerve myelinating cells that reconstitute the myelin coating after transplantation into myelin-deficient animals. Large scale culture technology for hESC can also be used to produce differentiated human cells such as insulin-producing pancreatic beta cells. This in recent years has lead Prof Revel to become involved in a novel commercial project—Kadimastem, a biotechnology company focused on the industrial development and commercialization of hESC-based products. One of their products, already in use by Merck-Serono, applies the hESC-derived myelinating cells in a drug-screening platform for new MS drugs.


Bioassociate: What do you feel has been the most rewarding accomplishment in your scientific career?

Prof Revel: The opportunity to pursue my basic science interests and to translate results into medical applications. I studied Interferons (IFN) as a translation control system which selectively inhibits viral protein synthesis. These studies required us to produce a lot of IFN and we therefore cloned the human gene for IFN-beta and developed the first efficient expression of this glycoprotein in mammalian cells. This attracted the attention of Serono, making it possible to develop IFN-beta production in their Israeli plant Interpharm, where I worked as Chief Scientist. Our studies on IFN-induced genes, in particular the HLA genes, shed new light on immuno-regulatory effects of IFN-beta which could be applied in autoimmune diseases. Serono’s clinical trials led to the registration of Rebif as an MS drug in 1998. To see one's research become a medication that helps hundreds of thousands of patients is indeed most rewarding.

Bioassociate: Tell us a little about your current project – KadimaStem

Prof Revel: This is really a continuation of our efforts to find new treatments for MS and other neurological diseases, by using pluripotent stem cells to produce cells that are damaged in such diseases.  We developed at the Weizmann Institute a procedure to derive human oligodendrocytes, and these myelinating cells can be applied to screen chemical libraries for molecules that stimulate nerve myelination. Present drugs for MS slow down the destruction of myelin by the immune system, but agents which stimulate the repair of myelin could be of great interest. The first product of Kadimastem, a three-year old biotechnology start-up at the Weizmann Science Park of which I am today the Chief Scientist, is such a drug screening platform already in use under contract with Merck Serono in their search for new oral drugs for treatment of MS.  A main project of Kadimastem is the production of pancreatic islet cells which could be applied in the future for cell replacement therapy in Diabetes. A third project is production of human astrocytes which hold promises for treatment of ALS, since ALS patients have abnormal astrocytes that do not anymore exert their neurotrophic functions. Kadimastem has a scientific staff of 25 (with 6 PhD researchers), and works with human embryonic stem cells and iPS cells licensed from Hadassah (from Prof. B. Reubinoff) and from Shaarei Zedek Medical centers.

Bioassociate: What do you think about the President’s recent initiative to make Israel a leading neurotech hub in 
the world?

Prof Revel: All initiatives to support and promote scientific research in Israel are welcome. A country is not measured by its size and Israel can be a big country by its contributions to Science and Technology. President Shimon Peres always understood this and his Israel Brain Hub initiative should therefore be taken seriously. Hopefully, the government, granting agencies and investment funds will listen to his appeal and make it happen. Financing academic and biotech research is one of the best investments for the State of Israel.

Bioassociate: Many people have said that Israel has been exceptionally successful at attaining scientific progress and commercializing scientific developments. Why do you think this is?

Prof Revel: The vision and support from generous donators in the Jewish Diaspora have given Israel the means to make important discoveries. Commercializing research is relatively easy in Israel, and technology transfer offices do help many scientists become involved in industry. Israel is excellent in the medical device sector, and it is no accident that analysts say that it is uniquely positioned to develop leadership in Brain-Machine interface and therapeutic neuro-stimulation devices. The pharmaceutical market is slower to grow mainly because it takes so much time to reach the market. But successes in developing new drugs can bring much larger returns, in the many billions of dollars, which should appeal to long-term investors. The two medications for multiple sclerosis coming out of Israel, Teva's Copaxone and Merck Serono/Interpharm’s Rebif, are examples that make the point. The Biotech drug, gene and cell therapy sector ought to be supported much more actively, with larger R&D budgets, and treated as national priority projects. Personally, I am proud that contributions to development of Israeli Biotechnology were mentioned in my Israel Prize and Emet prize awards.

Bioassociate: What do you think is today’s most important/pressing therapeutic area which neuroscience could address?

Prof Revel: Understanding the human brain is the new frontier following the genome project. For therapeutics, the main challenges are neuro-degenerative diseases like strokes, Alzheimer's disease, Parkinson's disease, ALS, neuropathies, spinal cord injuries and progressive forms of MS. There are many advances in these and other neurological diseases, with new drugs (e.g. Azilect of Teva, developed by Prof. Moussa Youdim), gene products (e.g. antisense RNA for myasthenia gravis of Prof. Hermona Soreq) and stem cell derived products (e.g. Hadassah stem cell pioneering trials in ALS patients of Prof. Karousis, BenHur and Slavin, and stem cell-derived astrocyte-like cells for ALS treatment being developed by Dr Daniel Offen at Brainstorm).

Bioassociate: Which obstacles do you perceive in Israel’s path to becoming a world leader in neurotechnology?

Prof Revel: The main obstacle is that the scientific potential of Israel is still not estimated at its real potential by government and Industry. Compared to other sectors in which receive millions of dollars in funding, many bio- laboratories and startups could thrive with five to ten millions, but lack the funds. Opportunities are lost due to lack of understanding of the needs of scientist. To become a world leader in neurotech, dedicated funds must be earmarked and long-term investments be encouraged by the Israeli government. The Industry and Trade Ministry's Chief Scientist Office is doing a marvelous job but it is not enough. The private business sector and large companies (e.g. Teva) ought to join hands with the government to create the real opportunities that will better exploit the human resources with which Israel is blessed.