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Israel: Stimulus Package

Turning stem cells into molecular mediators to initiate repair

After a 40-year career at the Weizmann Institute of Science in Rehovat, Israel, it was time for Michel Revel to retire. Instead, Revel, an internationally renowned biochemist and molecular geneticist who was 72 years old at the time, got down to business. Enlisting the help of five former Weizmann colleagues, he co-founded Kadimastem, a drug screening and regenerative medicine company, in late 2009, with investor Yossi Ben-Yossef.

Using proprietary technology, Kadimastem is working on potential treatments for multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and types 1 and 2 diabetes. Revel and his colleagues have developed a technique for transforming human pluripotent stem cells—cells with the ability to become any other kind of cell—into insulin-secreting cells, as well as a range of neural cells. For Revel, the chief scientist of the team that created Rebif, Merck Serono’s blockbuster MS drug, these latest efforts are a logical continuation of his work in the field. Indeed, they may even hold the potential for another blockbuster, considering that MS drugs generate US$10 billion a year, and just 1 percent of the diabetes market would exceed US$1 billion.

“All treatments for MS today, including Rebif, work by reducing autoimmune attacks, thereby slowing down the destruction of myelin, a coating that protects nerve cells,” Revel says. “We want to take this further by finding treatments that stimulate the body to repair the myelin coating. Pluripotent stem cells are very useful for this.”

While at Weizmann, Revel and his colleagues had already devised a procedure to differentiate human embryonic stem cells into myelin-forming oligodendrocytes very similar to those in the human brain. “We mimic these cells better than most, I think,” he says. Now his team has worked out a robust protocol to produce these human myelinating cells and use them as a drug-screening platform, based on functional human tissue rather than on rodent cells.

Kadimastem, in contract with Merck Serono, is using these human myelin-forming cells to look for chemical compounds that fuel the differentiation of such cells. “We have semi–high throughput systems with robots that can handle compounds, and a computerized microscope to analyze images and quantify results,” Revel says. “We have already found four classes of compounds that stimulate myelin formation.”

On the regenerative medicine front, Kadimastem aims to improve diabetes treatment using insulin-producing cells derived from pluripotent stem cells. Designed for patients with types 1 and 2 diabetes who require daily insulin injections, this technique would involve implanting patients with the insulin-secreting cells to eliminate the need for injections. The challenge for Revel and his team is in getting the stem cells to mature into functional cells that sense the amount of glucose in the blood and secrete insulin accordingly. If they succeed, they plan to encapsulate these differentiated cells in a device that could be implanted, for example, beneath the skin. Their hope is that this will save patients from years of insulin injections.

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