The latest research news as of April 2011:
Reactivated virus may contribute to ALS
Autopsy samples have shown a viral protein called HERV-K reverse transcriptase is much more prevalent in ALS brain samples than in brain samples obtained from people who died of other causes.
Although viruses like HERV-K normally lie dormant in the human genome and don’t replicate, it appears that HERV-K may reactivate in people with ALS. Much of the human genome is made up of pieces of viral genomes, and it’s likely the HERV-K genome inserted itself into the human genome many generations ago.
Renee Douville at Johns Hopkins University in Baltimore, and colleagues, published the findings in the January 2011 issue of Annals of Neurology. Avindra Nath at Hopkins coordinated the study team, which included Jeffrey Rothstein, director of the MDA/ALS Center at Hopkins. The study was funded by the National Institutes of Health (NIH).
Investigators examined brain tissue from 28 people who died of ALS and compared it to brain tissue from 12 people who died from other chronic systemic illnesses; 12 who died with Parkinson's disease; and 10 who died from accidents or other causes without any pre-existing systemic illness.
They found that the brains of those who died of ALS had significantly higher levels of the viral protein HERV-K reverse transcriptase than did samples from any of the other groups, and that the protein was located in specific areas of the brain known to be affected in ALS. Also, the viral protein was found in the same areas as another protein, TDP43, overproduction of which has been implicated in ALS pathology.
The unusual activation of HERV-K suggests that this virus could be part of the problem in sporadic ALS, the most common form of the disease and one for which the cause is unknown. Sporadic ALS accounts for 90 to 95 percent of cases, with familial (inherited) ALS accounting for the other 5 to 10 percent.
Previous studies have found reverse transcriptase in ALS patients’ serum, but they have not been tied to production by a specific onset of viral genetic instructions, as has this protein.
The findings open new possibilities for therapeutic targets in ALS, such as silencing the viral genetic instructions or the proteins made from these instructions. Further studies are needed to clarify the role of HERV-K reverse transcriptase (and perhaps other viral proteins) in the nervous system, and whether blocking them would be helpful.
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ALS Biopharma to test heat shock protein
In March, MDA awarded a grant totaling $250,000 over two years to the biotech firm ALS Biopharma, in Doylestown, Pa., for testing of a heat shock protein-based biological therapy for ALS.
Heat shock proteins (HSPs) are a class of naturally occurring proteins that help cells withstand various kinds of stress.
The award will enable ALS Biopharma to test two different drug candidates based on heat shock protein 70 (HSP70) in the SOD1 ALS mouse model. Preliminary studies have demonstrated that mice treated with HSP70 experienced delayed symptom onset and improved survival time as compared to mice treated with riluzole (Rilutek), the only drug currently approved for the treatment of ALS.
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Glialogix to test new glutamate inhibitor
MDA’s translational research program has awarded a grant totaling $268,000 to biotech firm Glialogix, of Larkspur, Calif., to test GLX1112, a new experimental treatment for ALS. The funds will support an approximately yearlong study to determine the safety and efficacy of the compound in mice with an ALS-like disease.
GLX1112 is a glutamate inhibitor. Excessive signaling by glutamate, a central nervous system neurotransmitter, is believed to play a role in ALS and other neurodegenerative diseases.
Glialogix is collaborating on the study with the nonprofit biotech ALS Therapy Development Institute (ALS TDI), of Cambridge, Mass., which also receives funding from MDA.
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$2 million to ALS TDI
MDA awarded $2 million in March 2011 to the ALS Therapy Development Institute (ALS TDI), Cambridge, Mass., to support the Institute’s ongoing drug development research. The new funding comes via MDA’s Augie’s Quest, an ALS research fundraising initiative, and brings the total amount MDA has awarded to the nonprofit biotech since 2007 to more than $23.4 million.
The new grant will support preclinical testing of four new compounds in the SOD1 mouse model of ALS. If successful, the new experimental therapies are likely to advance to human clinical trials. ALS TDI also will use the funds to help expand its research program to include the TDP43 mouse model of the disease.
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TDP43 mouse model to be focus of new study
MDA announced March 22, 2011, that it has partnered with the ALS Therapy Development Institute; the Alzheimer’s Drug Discovery Foundation (ADDF) in New York; and the Association for Frontotemporal Degeneration (AFTD), headquartered in Radnor, Pa., to fund ALS TDI’s characterization of the TDP43 research mouse model, which recapitulates a number of biological states and symptoms found in ALS and other neurodegenerative disorders.
The TDP43 mouse model, which carries a mutation in the gene for the TDP43 protein, was developed by MDA-supported scientists at Washington University School of Medicine in St. Louis.
Fleshing out the characteristics of the TDP43 mouse will enable TDI scientists (and others) to improve the quality of preclinical testing of new drugs that target TDP43 in animals. Better, more standardized testing in animal models then is expected to translate into a higher success rate for new drugs designed to target TDP43 in humans.
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Dexpramipexole trial under way
“EMPOWER,” a phase 3 clinical trial in ALS of a molecule called dexpramipexole, soon will open at study sites in 28 U.S. states and 10 European countries, under the auspices of the biotech firm Biogen Idec, headquartered in Weston, Mass.
Dexpramipexole was developed under the name KNS-760704 by Knopp Neurosciences (now part of Knopp Biosciences), in Pittsburgh. Knopp and Biogen Idec entered into an agreement Aug. 18, 2010, to continue development of the experimental treatment for ALS.
The molecule has demonstrated favorable effects in phase 1 and 2 human clinical trials. It appears to work by improving the function and efficiency of cellular “energy factories” called mitochondria.
The phase 3 trial will include approximately 800 people with ALS. Each participant will be randomly assigned to receive 150 mg twice daily of dexpramipexole or a placebo.
Researchers will assess the drug’s effects on survival and functional decline, and will characterize its pharmacokinetics (how the body handles the drug).
For details, contact the medical director for the EMPOWER study at Biogen Idec at ALSclinicaltrials@biogenidec.com.
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NP001 now in phase 2 trial
The biopharmaceutical company Neuraltus Pharmaceuticals of Palo Alto, Calif., has launched a phase 2 trial of NP001, a small molecule designed to modulate the immune system in ALS.
Researchers will examine the effects of low- and high-dose NP001 versus those of a placebo in approximately 105 people, ages 21 years to 80 years, with ALS.
For more information, including the specific inclusion and exclusion criteria used to determine eligibility for trial participation, and contact information for the nearest study site, visit ClinicalTrials.gov and search for “NCT01281631,” email Neuraltus President & CEO Andrew Gengos at email@example.com, or call (650) 424-1600.
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Stem cell safety trial moves forward
Biotechnology company Neuralstem, which is conducting a phase 1 clinical trial of its patented neural stem cells in people with ALS at Emory University in Atlanta, announced in February that analysis of safety data from the first nine trial participants is complete. The company will now move to the last group of ALS patients in this part of the trial.
Also in February, the company received FDA orphan-drug designation for its human spinal-cord-derived neural stem cells. For details about the trial, visit the Emory ALS Center website, or call (404) 778-7777 or (800) 753-6679.
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Participants still needed for ceftriaxone trial
A phase 3 trial of the drug ceftriaxone remains open to people with ALS who have had symptoms for less than three years. Ceftriaxone, an antibiotic in the cephalosporin family, may protect motor neurons from injury.
U.S. study sites are located in Arizona, California, Colorado, Connecticut, Florida, Georgia, Illinois, Indiana, Kansas, Kentucky, Massachusetts, Michigan, Minnesota, Missouri, Nebraska, New Jersey, New York, North Carolina, Ohio, Oregon, Pennsylvania, Tennessee, Texas, Utah, Vermont, Virginia and Washington, D.C. Canadian study sites are in Ontario, Quebec and Nova Scotia.
For more information, visit the Northeast ALS Consortium (NEALS) at and click on ceftriaxone. Or, contact Sarah Titus at firstname.lastname@example.org or (617) 726-1398.
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MDA National Scientific Conference focuses on five strategies
|MDA’s National Scientific Conference provided a venue for researchers, clinicians and industry leaders to share the latest science in neuromuscular disease research. All gathered on March 15 to flex their muscles in a show of strength for MDA’s “Make a Muscle, Make a Difference” campaign.
Some 300 researchers, clinicians, representatives from biotech and pharmaceutical industries, and trainees specializing in neuromuscular disease gathered in Las Vegas March 13-17, 2011, for a conference on five leading therapeutic strategies applicable to ALS and a number of other diseases in MDA’s program.
The strategies include using antisense oligonucleotides to block genetic instructions, stem cells to study or treat disease, and small molecules, proteins and genes as therapeutic agents.
The meeting, part of MDA’s new national conference series, brought together a host of leaders in ALS research and drug development, with the goal of facilitating advancement of experimental strategies from “microscope to marketplace.”
The majority of the presenters and many of the audience members were current or former MDA research grantees, or physicians at MDA-supported clinics.
For more information, view the conference agenda and summaries of the presentations. To learn how these therapeutic strategies are being applied in ALS, see Covering a Broad Canvas: The Search for ALS Treatments.
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