ALS Alert Newsletter | June

An Eye on Clinical Trials

Highlights of the clinical part of this year’s Packard symposium

As possible new targets and approaches for ALS treatment have begun to surface from basic science labs, more of them, fortunately, are finding their way into the human trials pipeline. The change isn’t massive but it’s real.

That’s why, this spring, a full third of the Packard annual symposium centered on human trials for ALS therapies—the results, of course, as well as the fine points of trial design and the underlying biology.

“It’s important that our basic scientists see how clinical trials are designed—Click here to see why— how they’re arranged, what the caveats are,” says Packard Director Jeff Rothstein at the symposium’s opening. “A synergy between basic and clinical science benefits research.” Next year, several days will be dedicated to clinical trials.

All of the speakers were from NEALS. The nonprofit Northeast ALS Consortium is a gathering of ALS investigators from 92 different academic institutions in the U.S., Canada and Ireland. NEALS dedicates itself to the highest quality clinical trials possible.

The Packard Center, by the way, played a key part in founding NEALS more than a decade ago. There’s a Packard presence on its board.

Scroll down for highlights of the clinical symposium:

Testing Lithium in ALS Patients Also on Riluzole

By now, the news of the North American lithium trials is old: Lithium apparently doesn’t slow ALS better than a placebo. Still, the trials were successful in a different way. Here's how.

CK 357: Accenting the Positive?

CK-2017357—or CK357 for short—is a small molecule with an apparent ability to activate muscle. Specifically, as shown in animal studies, the agent makes fast skeletal muscle fibers—those most affected by ALS—respond more strongly to stimuli.

That means the body has to expend less energy to make muscle contract.

“That’s why we’re investigating it as possibly useful for ALS, as well as some other conditions such as frailty,” says Will Chou, who with colleague Ullrich Schwertschlag, described the drug’s performance to date. Both are with the San Francisco biotech firm, Cytokinetics.

Schwertschlag described lab animal studies in which CK357 increased a muscle’s response to motor neuron activity. It magnified muscle power and lessened muscle fatigue. Chou reported on phase I human trials—various dosages of the drug with healthy people—with similar results and apparent low side-effects. The drug has been granted orphan drug status by the FDA.

CK357 may not affect the disease process, the two scientists say. But they’re testing the drug as something that could maximize muscle output with minimal effort—possibly improving patients’ quality of life. Now studies have moved on, under NEALS supervision, to a phase II trial in ALS patients.

Learn more

Update: First Human Stem Cell Spinal Injections

It’s a pared-down study, going very carefully, says lead researcher Jonathan Glass, but that’s a necessity when you’re testing the first surgery-based injections of neural stem cells into the spinal cords of ALS patients.
Glass, a Packard investigator and head of Emory University’s ALS Center, reported on the recently-begun phase I trial using the human-derived cells. “Our main goal in this early phase is to determine the safety of injecting neural stem cells into the spinal cord, and how safe it is to have the stem cells there,” Glass says. The study will proceed in five phases—with checks in-between—moving from the most seriously ill patients to those in earlier stages.

Patients receive immunosuppressing drugs to avoid rejection of the cells, but says Glass, “we need further study to see if it’s necessary and for how long.” The injected cells, he says, have a “low immunogenic potential” that might allow fewer or lower dose drugs.

As of June 1st, three patients have received injections to one side of the lumbar spinal cord and one bilaterally to that region. “All have recovered from the surgery and are doing well,” Glass reports.

Eva Feldman, with the University of Michigan, heads the trial nationally.

Learn more about the trial.

May the Better Drug Win

A new phase II trial starts this summer, an unusual study in that it involves giving ALS patients who participate one of two drugs—creatine or tamoxifen—with those on the latter divided into a high dose and lower dose group.

Both drugs extended life considerably in SOD1 or other mouse models of ALS. And both, in human trials, appeared safe. But efficacy of either drug in the human studies was murky. Tamoxifen appeared to offer a slight survival benefit at high doses in a small (results unpublished) trial. And an earlier small study of creatine seemed to increase survival in some people, but for the overall trial, the numbers weren’t significant.

The new trial isn’t designed to show if either drug cures or retards ALS so much as it aims to see which one might lean more in that direction. Using what’s called a “play the winner” design, the trial acts as a reliable, less-expensive way to advance the better drug for a larger phase III human study.

"ALS patients are happier,” says investigator Swati Aggarwal, “ because there’s no placebo arm.” And researchers like it because its tight design makes it easier to run—the relatively small number of patients will still show accurate results.