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NeuroNow - The Little Drug That Might

Spring 2010

The Little Drug That Might

Date: January 3, 2010

Jeff Rothstein
“In a field where there’s almost no therapy,” says Jeff Rothstein, “having a drug get this far really sharpens your interest.”

A drug called talampanel — it’s from a family of antianxiety drugs — may slow the muscle weakening that comes with ALS, according to a phase II study led by Hopkins neuro-researchers.

Results of a phase II trial usually aren’t the stuff of headlines. The early, small-scale studies aim to show if a drug appears safe and has some good effect. Phase IIs are strong on “maybe” as far as therapy goes, but weak on “definitely,” because the sample of patients tested is small.

But talampanel is an exception. Its crossing the hurdle is news because it’s for ALS — Lou Gehrig’s disease — the fatal illness without a good therapy. Only a handful of potential ALS drugs have passed phase II. “We’re watching talampanel,” says Hopkins neurologist/ neuroscientist Jeffrey Rothstein, “because the drug does appear to slow the progression of disabling symptoms.”

In the 39 patients who received it, the loss of major daily life activities such as speaking, walking and dressing slowed by some 30 percent when compared with patient controls given a placebo. They also lost muscle strength less rapidly.

“The effect isn’t overwhelming at the dosage used in this early trial,” Rothstein admits, “but having promising human data is reason enough to keep it in the drug pipeline so we can really find out how it performs for patients.” Based on that, talampanel has already moved to the larger, more powerful phase III studies.

There’s more. It happens that Rothstein directs the Robert Packard Center for ALS Research, an international body based at Hopkins and considered by most to be a model of its kind. Among other things, the organization makes unusual, savvy alliances with other groups that can speed its search for therapy.

Talampanel may benefit from one such link-up with the Northeast ALS Consortium, a national group of academic researchers that Rothstein helped start that has hugely improved the quality of ALS trials. For rare diseases like ALS, where research funding is often meager, designing trials tightly is crucial. “You often only get one shot to try a drug, and early trials are small,” Rothstein says.

It’s not typical, but the phase II work on talampanel was carried out several years ago — an unusual gap between the end of a study and reporting results in a journal. That’s because, in spite of the shining nugget of slowed loss of ability, patients didn’t live longer. That discouraged the sponsoring drug company.

But changing times may raise up “the little drug that might.” Both improved design and greater understanding of what results mean have tightened the multicenter phase III trials.

Moreover, a sea change is about to hit in the way scientists view ALS. “We’ve long known that not all ALS patients show the same symptoms, in the same order,” Rothstein says. “But until now, we haven’t had the tools to investigate if subtypes of the disease exist.” Now, new stem cell techniques are making possible the first cultures of nervous system cells from ALS patients. Not only will Rothstein and colleagues be able to see if the disease really does vary at the most basic level, but they hope to use such cultures to pick out which patients might benefit most from specific drugs like talampanel.

“We’re optimistic about ALS research,” he says, “in a way we haven’t been before.”

For information: 410-614-5972.

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