Reinventing drug discovery

Public release date: 18-Apr-2013 [ | E-mail | Share ]

Contact: B. D. Colen bd_colen@harvard.edu 617-413-1224 Harvard University

Cambridge, MA, April 18, 2013 - Using a new stem-cell based drug screening technology with the potential to reinvent and greatly reduce the cost of the way new pharmaceuticals are developed, Harvard Stem Cell Institute (HSCI) researchers have found a compound more effective in protecting the neurons killed in amyotrophic lateral sclerosis (ALS) Lou Gehrig's disease than two drugs that failed in human clinical trials after hundreds of millions of dollars had been invested in them.

The new stem cell screening technique developed by Lee Rubin, a member of HSCI's Executive Committee and a professor in Harvard's Department of Stem Cell and Regenerative Biology, successfully predicted that the two drugs that eventually failed in the third and final stage of human testing would, in fact, fail.

"It's a deep, dark secret of drug discovery that very few drugs have been tested on human-diseased cells before being tested in a live person," said Rubin, who heads HSCI's program in translational medicine.

"We were interested in the notion that we can use stem cells to correct that situation."

Rubin's model is built on an earlier proof-of-concept developed by HSCI Principal Faculty member Kevin Eggan, who demonstrated that it was possible to move a neuron-based disease into a laboratory dish using stem cells carrying the genes of patients with the disease.

In a paper published today in the journal Cell Stem Cell, Rubin lays out how he and his colleagues applied their new method of stem cell-based drug discovery to ALS. The disease is associated with the progressive death of motor neurons, which pass information between the brain and the muscles. As cells die, people with ALS experience weakness in their limbs followed by rapid paralysis and respiratory failure. The disease typically strikes later in life. Ten percent of cases are genetically predisposed, but for most patients there is no known trigger.

Rubin's lab began by first studying the disease in mice, growing billions of motor neurons from mouse embryonic stem cells, half normal and half with a genetic mutation known to cause ALS.

Investigators starved the cells of nutrients and then screened five thousand drug-like molecules to find any that would keep the motor neurons alive.

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Reinventing drug discovery