ALS Research Roundup January-March 2012

by ALSN Staff on Sun, 2012-01-01 12:00
Article Highlights:

Dexpramipexole shows efficacy in ALS

Newly published data confirm that in a two-part phase 2 clinical trial, the experimental therapy dexpramipexole showed dose-related slowing of symptom progression and increased survival time in people with ALS.

The new findings were published online Nov. 20, 2011, in Nature Medicine by principal investigator Merit Cudkowicz (director of the MDA/ALS Center at Massachusetts General Hospital in Boston and a member of MDA’s Medical Advisory Committee) and colleagues.

Based on trial results, dexpramipexole appears to be unique in that it both improves survival and slows symptom progression, the investigators wrote in their report. They noted that no other drug has shown a clinically significant effect in the decline of function in a properly controlled clinical trial, and no other study has shown effects on both function and mortality.

Riluzole (Rilutek) — the only drug presently approved for treatment of ALS by the U.S. Food and Drug Administration (FDA) — modestly extends life span but doesn’t cause significant improvement in function.

In the phase 2 trial, higher doses of dexpramipexole correlated with a slower rate of decline in function, based on the ALSFRS-R (ALS Functional Rating Scale — Revised), a widely used and validated measure of functional ability in ALS.

In part 1 of the study, the rate of functional decline in a group of participants receiving 300 milligrams of dexpramipexole was 31 percent lower than the rate of decline in those who were in the placebo group. In part 2, participants receiving 300 milligrams a day showed a 20.5 percent slower rate of functional decline compared to those taking 50 milligrams.

Mortality for participants in the 300-milligram group was 68 percent lower than in the 50-milligram group during the 24-week active phase in part 2 of the study.

Functional decline and mortality also were analyzed together using a Combined Assessment of Function and Survival (CAFS) test. Results indicated that the 300-milligram/day dose of dexpramipexole was significantly more effective than the 50-milligram/day dose.

In both parts of the study, dexpramipexole was found to be safe and well-tolerated when taken (orally) twice daily by trial participants. A temporary reduction in the number of white blood cells (neutropenia) was observed in a few participants and will be monitored in future trials, the investigators said.

“Results from this phase 2 study demonstrate why we’re so enthusiastic about the rapid advance of dexpramipexole to a phase 3 trial,” Cudkowicz said in a press release.

“EMPOWER,” a large-scale, global phase 3 clinical trial of dexpramipexole in ALS is under way at study sites in 28 U.S. states and 10 other countries. (Enrollment for the trial has closed.)

Substantial evidence of efficacy in the EMPOWER study will move dexpramipexole closer to FDA approval for treatment of ALS.

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CK-2017357 tested in combination with riluzole

South San Francisco biotechnology company Cytokinetics announced Nov. 1, 2011, that it has begun testing its experimental ALS therapy CK-2017357 in people with ALS who are taking riluzole (Rilutek). Riluzole is the only drug approved by the U.S. Food and Drug Administration (FDA) for treatment of ALS.

This marks Part B of a phase 2 trial of CK-2017357 in ALS that is testing safety and tolerability of the drug and assessing any effects on motor function, respiratory function, muscle strength or fatigue. CK-2017357 is designed to enhance muscle contraction. It was granted orphan drug status March 10, 2010, by the FDA. (Orphan drug status provides financial incentives for the development of drugs for rare diseases.)

In Part A of the trial, people with ALS who were not taking riluzole were randomly assigned to one of four groups in which they received daily oral doses of placebo (inert substance), or CK-2017357 at a dose of 125, 250 or 375 milligrams, for two weeks.

Part B will follow the same treatment schedule; in addition, each participant also will take 50 milligrams of riluzole.

In the first group, clinical assessments took place at scheduled intervals during the two-week treatment phase, and again one week after the final dose. The same assessment schedule is planned for the B group.

For details on participating in the trial, contact Jean Masonek at, or enter NCT01378676 into the search box at

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Stem cell injections move to cervical region of spinal cord

Neck x-ray

Injection of neural stem cells into the cervical (neck) region of the spinal cord is being tested in people with ALS.

Maryland biotherapeutics company Neuralstem announced Oct. 24, 2011, that it has received approval from the U.S. Food and Drug Administration (FDA) to begin transplanting stem cells into the cervical (neck) region of people with ALS.

This first U.S.-based trial of neural stem cells in ALS opened at Emory University in Atlanta, Ga., in January 2010. It’s designed to assess the safety of Neuralstem’s spinal cord neural stem cells and intraspinal transplantation method in people with ALS.

Testing has progressed through increasing levels of risk. After reporting “smooth progress” in June 2011 for the first 12 trial participants, who received transplantations into the lumbar (lower back) region of the spinal cord, Neuralstem sought FDA approval to begin transplantation in the cervical spinal cord region.

Now, three people with ALS will receive injections on one side of the cervical region of the spinal cord. If results are favorable, the final three trial participants will receive injections on both sides of the cervical region.

Although the study is a safety trial, it is hoped that cervical injections may help with breathing and swallowing in ALS. Study investigators plan to evaluate any effects on motor and respiratory function.

Enrollment for this trial is still open; however, in addition to other criteria, only those who live in close proximity to Emory University will be considered for the trial. For details, contact Meraida Polak at, or call (404) 778-3754; or, enter NCT01348451 into the search box at

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'Aberrant astrocytes' kill motor neurons

aberrant astrocytes, AbA cells
Aberrant astrocytes, or AbA cells, appear to help drive the progression of ALS.

A multinational team of scientists has identified a specific type of astrocyte that behaves abnormally, causing degeneration and death in motor neurons in rats with a disease resembling familial SOD1-related ALS. (Astrocytes normally function as nervous system support cells.)

The astrocyctes have been named “aberrant astrocytes,” or AbA cells, by the research team, comprised of scientists from institutions in Montevideo, Uruguay, and Oregon State University in Corvallis.

The researchers found that the cells are present in large numbers during disease progression, and that they typically reside close to motor neurons (nerve cells that control muscles). In addition, the researchers noted an “unprecedented toxicity” to motor neurons via the release of toxic factors that prohibit growth or survival of the muscle-controlling cells.

The findings were reported online Oct. 18, 2011, in Proceedings of the National Academy of Sciences.

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Evidence builds for astrocyte involvement in ALS

An MDA-supported team of scientists has demonstrated in rats that nervous system support cells called astrocytes carrying an SOD1 mutation cause neighboring motor neurons to deteriorate and die.

The finding adds to a growing body of evidence that the star-shaped cells play a key role in the motor neuron degeneration that is the hallmark of ALS. Astrocytes normally support and protect motor neurons.

The team, which included MDA grantee Nicholas Maragakis, reported its findings online Oct. 3, 2011, in Proceedings of the National Academy of Sciences.

In a series of studies, the researchers took astrocyte “precursor” cells from the developing spinal cords of research mice carrying a human, ALS-associated SOD1 mutation and injected them into the spinal cords of healthy rats. The cells settled into their new surroundings and developed into astrocytes, around which the investigators observed motor neuron degeneration and death.

The rats also developed signs of motor neuron disease, including weakness in the front legs and respiratory problems.

For more on astrocyte involvement in ALS, see ALS: Not Just About Motor Neurons Anymore, MDA/ALS Newsmagazine, May-June 2010.

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Online familial ALS registry opens

The Web-based fALS Connect registry for people with the familial, or inherited, form of ALS has launched. Membership is voluntary, and is limited to those who have familial ALS and their blood relatives.

MDA grantee Michael Benatar helped develop the registry and says one of the major goals of the project is to enhance research. Benatar worked to get the project up and running both as part of a University of Miami Miller School of Medicine (Florida) research team, and also in his capacity as chair of the Northeast ALS (NEALS) Consortium fALS working group. He’s received MDA support to study the early stages (prior to symptom onset) of familial ALS since 2007.

“FALS Connect is something we developed to help bring the familial ALS community — affected individuals and family members potentially at risk — together and to facilitate communication between the patients and the researchers,” Benatar said.

Registration takes only a few minutes. Participation involves creating an online account; completing a profile containing information about genetic testing and the effects of ALS on the family; and keeping the profile updated.

Members may be contacted about opportunities to be involved in research.

Private information will be stored in a secure database and will not be shared, but information from which all identifying data have been stripped may be shared with other registry members and with ALS research scientists.

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ALSN Staff
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