- A genetic test for ALS caused by a mutation in the C9ORF72 gene is available April 30.
- A new component of the National ALS Registry will enable scientists to use registry data in ALS research.
- Cytokinetics' experimental ALS therapy CK-2017357 proves safe and well-tolerated when administered with riluzole, and in twice-daily dosing.
Among the reports given at the 2012 annual meeting of the American Academy of Neurology, being held April 21-28 in New Orleans, was information about research into amyotrophic lateral sclerosis (ALS).
C9ORF72 genetic test for ALS
The Athena Diagnostics division of Quest Diagnostics soon will offer the first clinically available testing service designed to detect the C9ORF72 repeat expansion mutation that can cause both ALS and frontotemporal dementia (FTD).
The C9ORF72 mutation was identified in September 2011 and appears to be the most common known cause of familial ALS, FTD, and ALS with FTD. The mutation underlies approximately 40 percent of familial ALS cases, and also has been found to be responsible for about 8 percent of sporadic ALS. (Familial ALS refers to situations in which there is more than one known occurence of ALS in the family; sporadic ALS refers to situations in which there is no known occurence of the disease in other family members.)
The new genetic test is offered to help speed the diagnosis of ALS. It will be available to clinicians as a standalone test, or as part of multigene testing, on April 30.
For testing locations, visit the National Center for Biotechnology Information's Genetic Testing Registry.
Those considering genetic testing should speak with their physician. Consultation with a genetic counselor, who can help obtain and interpret the results of genetic testing, is recommended.
New clinical research component part of National ALS Registry
A clinical research notification component is being integrated into the National ALS Registry, a national database of information from individuals affected by ALS. The new feature, which will allow ALS investigators to search and use registry data for research, is scheduled to become active in May 2012.
Researchers interested in registry data will need to apply to the CDC for permission. If approved, they will be able to search the registry database using criteria such as age range or geographical location. To maintain the privacy of registry members, all data shared with researchers will be stripped of identifying information.
Researchers also will be able to let registry members know about clinical trials or other studies that might be particularly suited to them. Registry officials will send information to those who qualify, and anyone who is interested may choose to respond.
The registry, which is sponsored by the U.S. Centers for Disease Control and Prevention, opened in October 2010. Registry data is expected to help researchers in their search for the causes of, and therapies for, ALS.
Encouraging results from two phase 2 trials of CK-2017357
In the second stage of a phase 2 clinical trial in people with ALS, CK-2017357 proved safe and well-tolerated when administered with riluzole. (Riluzole is the only drug approved by the U.S. Food and Drug Administration for treatment of ALS.)
Trial investigators also found that levels of CK-2017357 in the blood were unaffected when given in combination with riluzole; levels of riluzole, however, increased.
The two stages of the trial were designed to evaluate the safety and tolerability of CK-2017357, an experimental therapy for ALS from South San Francisco-based Cytokinetics, at different doses and dosing schedules, with and without riluzole.
In each stage, 24 people with ALS received daily oral doses of a placebo (fake drug) or CK-2017357 at 125 milligrams per day, 250 milligrams per day or 350 milligrams per day, for two weeks. Those in the first stage did not take riluzole, while those in the second stage took 50 milligrams of the drug per day.
Although dizziness was reported in both stages of the trial by some participants who received CK-2017357 (and by none who received placebo), it generally was mild and went away with continued treatment.
The trial was not designed to measure efficacy of CK-2017357, but dose-dependent, clinically meaningful positive trends were observed in motor and pulmonary function in both stages. (Motor function was assessed using the ALS Functional Rating Scale-Revised, a clinically validated instrument designed to measure disease progression and changes in functional status in people with ALS. Pulmonary function was assessed by measuring the maximum volume of air a person can inhale and exhale.)
CK-2017357 is designed to work by increasing muscle sensitivity to calcium, which in turn is expected to increase skeletal muscle force and improve muscle function.
In the first stage of the phase 2 clinical trial, the drug was found to be safe and well-tolerated in people with ALS who did not take riluzole. Trial participants who received the highest dose showed improved scores on tests that measure motor and breathing function, muscle strength and fatigue.
Jeremy Shefner, director of the MDA/ALS Center at SUNY Upstate Medical University in Syracuse, N.Y., reported the findings.
In a different phase 2 trial, CK-2017357 was generally safe and well-tolerated when given twice daily to 21 people with ALS who were taking riluzole. (Six trial participants received placebo.)
Most trial participants receiving the experimental therapy were able to take the drug in doses that were increased from 125 milligrams twice daily to 250 milligrams twice a day, over a period of three weeks. As in the two-part, single-dose study that tested safety and tolerability of CK-2017357 with and without riluzole, trends indicating functional improvement were observed.
Dizziness was the most reported side effect. It was observed in 12 of the 21 participants who took CK-2017357, and in none of those who received placebo. In 10 of the 12 it was mild; the other two participants reported moderate dizziness.
For more on both trials, read Cytokinetics Announces Encouraging Results From Two Phase 2 Clinical Trials Evaluating CK-2017357 in Patients with Amyotrophic Lateral Sclerosis.
Cytokinetics announced April 19 that CK-2017357 received a fast-track designation for ALS from the U.S. Food and Drug Administration.