News on the latest research, as of June 2010
Neuraltus targeting immune system cells
Neuraltus Pharmaceuticals, of Palo Alto, Calif., is developing a small molecule whose target is regulation of immune system cells believed to contribute to neuroinflammation and disease progression in ALS.
According to Andrew Gengos, president and CEO of Neuraltus, the company’s experimental drug NP001 is designed to be administered intravenously and to flip a molecular switch in cells known as macrophages in the blood and microglia in the central nervous system. “There’s a switch that it hits,” Gengos said, “that regulates these cells from an activated, inflammatory mode back to a more normal, wound-healing mode.” (For more about this phenomenon, see “ALS: Not Just About Motor Neurons Anymore,” in the May-June 2010 ALS Newsmagazine.)
Neuraltus is completing mouse studies and hopes to conduct a phase 1 safety trial of NP001 in people with ALS by the fall of this year.
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Stem cell trial at Emory on track
So far, four people with ALS have received injections of neural stem cells into their spinal cords at Emory University in Atlanta, and all are “doing quite well as of now,” reported study investigator Jonathan Glass in late May 2010. Glass directs the MDA/ALS Center at Emory.
This phase 1 trial, which got under way late last year, is not designed to evaluate benefit. It will test the safety of fetal-derived stem cells that have partially matured into nerve cells, as well as the safety and feasibility of the spinal cord injection procedure. (See “First U.S. trial of neural stem cells in ALS gets FDA green light,” ALS Newsmagazine, November-December 2009.)
The trial is being funded and managed by Neuralstem, a Rockville, Md., biotherapeutics company, which has a patent-protected technology to produce neural stem cells.
In a May 28 webinar on ALS research, Glass explained how the Neuralstem trial is carefully designed to progress through increasing levels of risk, depending on safety results at each stage.
The concerns are not just limited to the effects of the cells themselves, Glass noted. In addition, there’s the safety and tolerability of the surgical procedure; the possible toxicities of the immunosuppressant drugs the participants are receiving to help them tolerate cells that are not their own; and the potential for the development of pain, new weakness or incontinence as a result of the injections.
“The FDA [Food and Drug Administration] tells us when and if it’s safe to move on,” he said.
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Participants needed for biomarker study
Investigators at approximately 30 institutions are seeking participants with and without ALS to identify biological indicators (“biomarkers”) unique to the disease in the blood and spinal fluid. Biomarkers are considered vital to improve ALS diagnosis and to monitor response to treatments. A total of 650 blood and 300 spinal fluid samples will be collected from healthy people, people with ALS, and people with diseases mimicking ALS, at an initial visit and, for those with ALS, after six, 12 and 18 months.
The study’s principal investigator is Merit Cudkowicz, who directs the MDA/ALS Center at Massachusetts General Hospital in Boston. Contact Daniela Grasso at (617) 726-0842 or email@example.com. For details and a complete list of study sites, see the Northeast ALS Consortium site.
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Work of breathing is being studied
Researchers at the MDA/ALS Center of Hope at Drexel University in Philadelphia, coordinated by Center director Terry Heiman-Patterson, are seeking adults with ALS for a study of how many calories they use while at rest with no breathing assistance; while at rest and using noninvasive ventilation; and at rest and breathing against resistance.
One goal of the research is to see whether caloric intake should be reduced after starting assisted ventilation. The investigators are seeking people with ALS ages 20-85 whose disease has progressed over the preceding six months, but who have had symptoms for less than five years. Contact Christine Barr at (215) 762-5186 or firstname.lastname@example.org.
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Talampanel fails to slow functional loss
The oral drug talampanel has failed to slow disease progression in a large, phase 2 trial in ALS, according to an announcement by Teva Pharmaceuticals on May 17. Teva, based in Jerusalem, has been testing this glutamate-inhibiting molecule in ALS.
Talampanel is designed to block AMPA receptors, a type of molecular docking site for glutamate (a transmitter of signals in the nervous system). An excess of glutamate has been implicated as a possible contributor to ALS.
Teva conducted a multinational, multicenter study of talampanel, in which 559 people with ALS were randomly assigned to receive either a placebo, 50 milligrams of talampanel or 25 milligrams of talampanel three times per day. The investigators were looking for a change from baseline in the revised ALS Functional Rating Scale (ALSFRS-R), a standard scale for monitoring functional abilities in ALS.
They found that, while talampanel was apparently safe, it did not reduce disease-related functional deterioration.
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Ceftriaxone trial is still open
A 600-person trial of intravenous ceftriaxone, an antibiotic, remains open at several North American sites. Laboratory studies suggest the drug protects motor neurons from injury. Participants’ ALS symptoms must have existed for no more than three years. Inclusion criteria include a vital capacity (breathing measurement) of at least 60 percent of normal and a caregiver to help administer study medication. Contact Sarah Titus, assistant project manager, at (617) 726-1398, or email@example.com. For all site contacts, see www.alsconsortium.org.
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