ALS Briefs: NurOwn, Disease Modifiers, Biomarker Test

by Amy Madsen on Wed, 2013-10-09 05:00

Three short items about the state of ALS science: BrainStorm’s upcoming US stem-cell trial; modifying ALS progression; a blood-based biomarker test

This roundup of recent amyotrophic lateral sclerosis (ALS) research and clinical trials news includes:

BrainStorm Cell Therapeutics prepares for US stem cell trial

Update (Dec. 11, 2013): In a Dec. 10, 2013, press release, BrainStorm reported on preliminary results of its phase 2 trial of NurOwn stem cells, which is being conducted in Jerusalem. Principal investigator Dimitrios Karussis, who presented the data at an ALS meeting in Milan and is quoted in the press release, said the safety data are "impressively positive," with only minimal and transient adverse events; and that a numer of patients showed some initial indications of clinical improvement. In a Dec. 11, 2013, press release, the company said it has received an $800,000 grant from the Office of the Chief Scientist in Israel's Ministry of Industry, Trade and Labor to support development of NurOwn stem cell therapy.

BrainStorm Cell Therapeutics has identified treatment production facilities in preparation for its U.S.-based, phase 2a trial to test the company’s NurOwn stem cell technology in people with ALS. The Dana Farber Cancer Institute (DFCI) will produce the cells that will be used at two trial sites: Massachusetts General Hospital in Boston, and the University of Massachusetts Medical School in Worcester, Mass. The third site in the trial, the Mayo Clinic in Rochester, Minn., will produce NurOwn at its own facility.

BrainStorm’s NurOwn technology uses mesenchymal stem cells, taken from a person’s bone marrow and coaxed to develop into healthy cells capable of delivering neurotrophic factors (molecules that support motor neurons, the nerve cells that die in ALS). The healthy cells are then readministered to the people from whom they were taken.

A phase 2 trial of BrainStorm’s NurOwn stem cells in ALS is ongoing at the Hadassah Medical Center in Jerusalem. For information, see Autologous Cultured Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in Patients With Amyotrophic Lateral Sclerosis (ALS), or enter NCT01777646 into the search box at ClinicalTrials.gov.

Motor neuron changes at ALS onset determine disease course

Specific changes in motor neurons at the onset of ALS appear to play a key role in determining the course of the disease, reports a team of researchers based in the United Kingdom and Italy.

Caterina Bendotti at the Mario Negri Institute for Pharmacological Research in Milan, Italy, and colleagues, showed that the ability of motor neurons to activate immunological defense mechanisms and other protective mechanisms in response to cell stress was associated with slower disease progression in a mouse model of ALS. In contrast, when these mechanisms were less robustly activated, the mice had a more aggressive disease course. The findings support the hypothesis that immune system activity plays a significant role in modulating ALS progression, and they suggest that therapeutic strategies designed to modulate the immune system response in ALS may involve dampening the activity of some pathways while boosting it in other pathways.

The identification of key genes and pathways likely to account for the severity of the ALS disease course in the mice may in turn help identify similar modulators of disease progression in human ALS, revealing biological targets at which to aim therapies that could slow the disease.

The team published its findings Sept. 24, 2013, in Brain. See Transcriptomic Indices of Fast and Slow Disease Progression in Two Mouse Models of Amyotrophic Lateral Sclerosis.

Blood test for a biomarker

A multinational research team has developed a test that is able to reliably and accurately measure levels of a protein called Neurofilament Light (NFL) — a biological indicator, or biomarker, of neurodegeneration — in human blood samples.

A commercially available test to measure NFL protein levels in cerebrospinal fluid samples exists, but getting these samples is difficult. The new method allows for scientists instead to measure NFL levels in blood, which is far easier to obtain.

In studies, the team’s electrochemiluminescence (ECL)-based test detected higher blood levels of NFL protein in 46 people with ALS than in a control group of 67 healthy people and in 68 neurological patients who showed no evidence of structural central nervous system damage. The team says its data support further studies of blood NFL protein levels as a biomarker to predict and monitor progression of neurodegenerative disease and for assessing the effects of experimental treatments in clinical trials.

Johanna Gaiottino at Queen Mary University of London (United Kingdom), and colleagues, published their findings online Sept. 20, 2013, in PLoS One. See Increased Neurofilament Light Chain Blood Levels in Neurodegenerative Neurological Diseases.

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