January 18, 2007

Our Five-Year Plan? Let Human Cells EXcellerate Therapy

This winter the Packard Center takes a determined stride toward therapy with EXcellerate, an endeavor sparked by recent finds from its laboratories and notable advances in its scientific techniques.

As the Center’s newest arm, EXcellerate features an updated, more aggressive approach to ALS therapeutics. “We’re driven to it,” says Director Jeffrey Rothstein, “because science’s use of the classic SOD1 mouse model hasn’t proven effective.”

EXcellerate’s initial phase—drug discovery—relies on Center scientists’ ability to prod human stem cells into becoming motor neurons or other cell types involved in ALS. By mimicking ALS’s effects on each cell variety, they’ll make the first true human-based models of the disease. Then they’ll test them with available drugs—ones FDA-approved for other illnesses—under an unusual two-drug matrix design that raises chances of discovering helpful drug combinations.

“This is also the first use of human stem cells to help screen ALS drugs,” says Rothstein. And it’s a first for the “combinatorial” matrix to spot therapy for motor neuron disease. “People have looked at single drugs before,” he adds, “but by investigating two drugs at a time, we can flush out synergies.”


When Packard scientist John Gearhart brought the Center his human embryonic stem cell cultures, he couldn’t know how fast they’d trip human-based models of ALS.

Partnerships should hasten the search. One, with Hopkins’ Project Restore, brings their expertise in culturing and analyzing human and rodent embryonic stem cells. Project Restore is a respected research group bent on therapies for the nervous system diseases transverse myelitis and multiple sclerosis.

Biotechnology companies will also sign on as EXcellerate partners. With their years of experience in drug discovery, plus Packard’s lineup of disease-testing models, there’s a promise of results. And because screening masses of drugs with a combination matrix demands the technology to test hundreds of cell samples simultaneously as well as software to explain thousands of data points, the Center welcomes the services of Hopkins’ High Throughput Biology Center.

Later, EXcellerate will turn to improving drug delivery and uncovering much-needed biological signposts, or markers. Markers would sharpen diagnosis and provide ways to monitor therapy. “We’ve known we need something better,” says Rothstein, “and we’ve worked up to this next step. It’s high time.”



http://www.packardcenter.org/