This roundup of recent amyotrophic lateral sclerosis (ALS) research and clinical trials news includes:
First patient treated in Neuralstem phase 2 trial
Update (Aug. 4, 2014): The phase 2 trial of NSI-566 spinal cord-derived stem cells for the treatment of ALS is closed, with the last patient having received stem cell injections, according to an Aug. 4, 2014, press release from Neuralstem. Results, including six months of follow-up data, are expected in early 2015.
Neuralstem Inc., announced in a Sept. 10, 2013, press release that the first patient has been treated in its phase 2 trial of NSI-566 spinal cord-derived neural stem cells in the treatment of ALS at Emory University Hospital in Atlanta, Ga. Neural stem cells generate muscle-controlling nerve cells (motor neurons) and glia (a type of motor neuron support cell) in the brain. The trial, which is designed to assess safety and determine the maximum tolerated dose, is taking place at the MDA/ALS Center at Emory, with principal investigator Jonathan Glass; and at the ALS Clinic at the University of Michigan Health System in Ann Arbor, with principal investigator Eva Feldman. It's hoped the experimental therapy will improve respiratory function and prolong life in ALS.
For more information on this trial, see Dose Escalation and Safety Study of Human Spinal Cord Derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis, or enter NCT01730716 into the search box at ClinicalTrials.gov.
Tirasemtiv phase 2 trial results published
South San Francisco biotechnology company Cytokinetics announced in an Aug. 22, 2013, press release the publication of two papers detailing previously reported data from phase 2 clinical trials of Tirasemtiv (formerly CK-2017357) in people with ALS.
A Study to Evaluate Safety and Tolerability of Repeated Doses of Tirasemtiv in Patients with Amyotrophic Lateral Sclerosis, published online Aug. 19, 2013, in Amyotrophic Lateral Sclerosis, reports data from two clinical trials (see trial IDs NCT01378676 and NCT01486849 at ClinicalTrials.gov.) in which the drug appeared to be safe and well-tolerated at doses up to 500 milligrams per day, including in participants who also were being treated with 50 milligrams per day of riluzole (the only drug approved by the U.S. Food and Drug Administration to treat ALS).
The Relationship Between Tirasemtiv Serum Concentration and Functional Outcomes in Patients with ALS, published online Aug. 19, 2013, in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia, reports apparent concentration-dependent effects on both function and measures of strength and endurance when tirasemtiv was administered to trial participants for up to 21 days.
The authors from both studies say their findings support further development and testing of tirasemtiv for the potential treatment of ALS. (Tirasemtiv currently is being tested in a phase 2b, 400-person, multinational clinical trial in people with ALS; for trial information, enrollment criteria and contact information, see Study of Safety, Tolerability and Efficacy of CK-2017357 in Amyotrophic Lateral Sclerosis.)
High-calorie foods and ALS
In a 26-person study conducted in people with ALS who had lost weight, a team of researchers at University of Ulm (Germany) reports that body weight was stabilized after 12 weeks of treatment with either of two high-calorie supplements — one with high fat content, and the other with high carbohydrate content. Albert C. Ludolph and colleagues noted that the high-fat supplement had a greater (but not statistically significant) effect than did the supplement containing high levels of carbohydrates, but concluded that both types of supplement are suitable for stabilizing body weight in ALS.
Based on evidence that associates weight loss with shorter survival time in ALS, the researchers suggest it may be possible that a high-calorie food supplement could improve survival in those with the disease — a hypothesis, they say, that can only be tested by conducting further studies. The team published its findings online Aug. 14, 2013, in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.
Autoimmune disease and ALS
Some autoimmune disorders are associated with a small increase in the risk of later developing ALS, reports a team of researchers at Oxford University in the United Kingdom. In a study using hospital records spanning from 1999 through 2011, Michael Goldacre and colleagues found that there were significantly more cases than expected of ALS associated with a prior diagnosis of the autoimmune disorders asthma, celiac disease, younger-onset diabetes (younger than 30 years), multiple sclerosis, myasthenia gravis (MG), myxedema, polymyositis (PM), Sjögren syndrome, lupus and ulcerative colitis.
The results, published online Aug. 14, 2013, in Neurology, may provide support to the hypothesis that dysregulation of the immune system plays a role in ALS, but a direct causal link between autoimmune mechanisms and development of ALS remains unclear. The team notes that the link between some autoimmune conditions and ALS suggests the possibility of shared genetic or environmental risk factors.
Power of induced pluripotent stem cells
Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed back to a stem-cell-like state, where they can then be coaxed along a desired path of development to become a specific cell type — one of the most promising of which is motor neurons.
Clive Svendsen, director of the Regenerative Medicine Institute at Cedars-Sinai Medical Center in Los Angeles, reviews the potential for iPSCs to advance knowledge of human disease and potential treatments, including in such areas as disease modeling and target identification for therapy development. See Back to the Future: How Human Induced Pluripotent Stem Cells Will Transform Regenerative Medicine, published Aug. 20, 2013, in Human Molecular Genetics. For more about the use of stem cells in ALS research, read blog posts by Svendsen in Stem Cells and Hope in ALS, Part 1 and Part 2.
ALS TDI partners with Anida Pharma
The nonprofit biotech ALS Therapy Development Institute (ALS TDI) announced in a Sept. 10, 2013, press release that it has entered into a research partnership with Anida Pharma Inc. to investigate a potential treatment for ALS. Under the terms of the agreement with Anida, ALS TDI will test whether treatment with the compound Neuroprotectin D1 (NPD1) has any functional benefit in the SOD1 research mouse model of ALS. NPD1, also referred to as Protectin D1 (PD1), helps control neuroinflammation and prevent cell death, but also has trophic (nourishing) effects. MDA and ALS TDI have maintained a strategic research partnership since January 2007, creating the largest ALS drug discovery project in history.