From: alscenter@jhmi.edu

To: The ALS Community

Date: November 7, 2007

Subject: Robert Packard Center ALS News Network


CINQUE FOUNDATION GIVES $1.5 MILLION GRANT TO ROBERT PACKARD CENTER FOR ALS RESEARCH AT JOHNS HOPKINS
Grant seeds innovative drug discovery for ALS and other motor neuron diseases

Baltimore, MD - Nov. 7, 2007 - A $1.5 Million grant from the Cinque Foundation will enable scientists working at the Robert Packard Center for ALS Research at Johns Hopkins to develop an innovative approach to drug discovery using human embryonic stem cells in their search for treatments for amyotrophic lateral sclerosis (ALS). The funding gives new drug discovery for ALS and other motor neuron diseases its start, as part of the Packard Center's "ExCellerate" program, a special initiative dedicated to expediting the discovery of treatments for ALS and other motor neuron diseases.

ALS is a fatal disease, which strikes 5,000 Americans each year and is one of the world's most common neuromuscular diseases. Presently, treatment is limited to palliative care - there is no cure.

A team of scientists led by Packard Center Director Jeffrey Rothstein, M.D., has been preparing human stem cells as a basic tool to help reveal new therapies. They have devised a novel way to use the cells to screen thousands of drugs approved previously by the FDA for treatment of other diseases. Because FDA-approved drugs have already undergone extensive safety testing for clinical use, a candidate drug from among them, identified as "new use" by the FDA, can be expedited to clinical trial.

Rothstein's team will look at drugs that improve several activities disrupted in ALS, both in motor neurons and in nerve cells called astrocytes. Recent Packard Center research has shown that damage to astrocytes represents the bulk of motor neuron injury in ALS. The scientists will also look for drugs that inhibit ALS-related inflammation, another very important and toxic process in the disease.

The Cinque grant supports Hopkins scientists as they assemble the highest-tech system possible for screening drugs. Previously, Rothstein's team - in a wide but preliminary screening venture coordinated by the National Institutes of Health - identified ceftriaxone. The drug was then ushered, in record time, into clinical trials for ALS treatment.

That first effort tested the effects of single drugs on cell cultures or slices of spinal cord from a rat model of ALS. It might easily have missed a helpful synergy between two or more of the drugs.

The Cinque-funded ExCellerate project will advance screening technology significantly, making it possible to check multiple drugs for multiple behaviors. Rothstein and his ExCellerate team are designing a special matrix that maps ways to test millions of two-drug interactions. And since the concentration of an agent can make a huge difference in biological systems, the matrix will also include many different dilutions of the drugs in the pairings. ALS and spinal muscular atrophy are the chosen targets to test this innovative matrix for screening drugs.

"No one has done this before," says Rothstein, "and while we have chosen ALS as our first target for farming FDA-approved drugs, the matrix we create could become a very useful method to screen drugs for many other diseases. Our matrix should shave years off of the research time required to deliver drugs for clinical testing, delivering the benefits of medical research to patients sooner than has been the possible with conventional drug discovery."

To build this matrix and search for ALS drugs, Rothstein will collaborate with Johns Hopkins' new, state-of-the-art High-Throughput Biology Center. The HIT Center offers staff expert in developing drug assays and access to automated processes that increase screening capacity and efficiency. Some of the effort will also be subcontracted to experienced biotech companies, to hasten sharing of findings to major collaborators in the field.

Payment of the $1.5 million, three-year grant might be expedited as research milestones agreed upon by the Cinque Foundation and Rothstein are reached. The ExCellerate program operates on entrepreneurial standards with the belief that this approach will increase focus and hasten discovery.

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About the Cinque Foundation. Established in 2007, the Cinque Foundation is dedicated to eliminating suffering and death caused by ALS, also known as Lou Gehrig's disease. The Foundation funds medical research that contributes to the understanding of this complex disease, with a particular emphasis on expediting the translation of promising results to benefit ALS patients.

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About the Robert Packard Center for ALS Research. Headquartered in Baltimore, the Robert Packard Center for ALS Research at Johns Hopkins is a collaboration of scientists worldwide, who are working aggressively to develop new treatments and a cure for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. The Center is the only institution of its kind dedicated solely to the disease. Its research is meant to translate from the laboratory bench to the clinic in record time.

For more information about The Robert Packard Center for ALS Research at Johns Hopkins, including information on its latest research and treatment, visit www.alscenter.org