ALS Research Roundup July-August 2011

by ALSN Staff on Fri, 2011-07-01 13:37
Complex interaction: The amount of energy people with ALS expend on a daily basis varies at different stages of the disease and is affected by numerous physical factors. Two of these — nutrition and respiration — appear to work synergistically with resulting positive or negative effects.
Article Highlights:

Eating and breathing: A possible 'synergistic' effect in ALS

Initial results of a multicenter pilot study to evaluate nutritional requirements and early intervention for breathing problems in ALS are helping scientists determine how physical factors such as body mass, diet and activity affect the total daily energy expenditure of people with ALS at different stages of the disease.

Neurologist Edward Kasarskis, professor of neurology, toxicology and nutrition at the University of Kentucky in Lexington, and colleagues, reported preliminary results in the January issue of Amyotrophic Lateral Sclerosis.

The study is designed to determine factors contributing to energy; evaluate nutrition in ALS; and investigate the effects of noninvasive positive pressure ventilation (NIPPV) used for respiratory support in ALS.

Although optimal nutrition and ventilatory function in ALS may appear to be unrelated issues, the investigators noted that each may affect the other and provide “synergistic” benefits overall.

For example, NIPPV used through the night might reduce the number of calories burned during the day. Also, lack of energy translates to muscle weakness and fatigue, and a poor diet can adversely affect the structure and function of the diaphragm (a major respiratory muscle located under the ribcage).

Further analysis of the initial findings will enable the research team to:

  • develop two approaches for pinpointing the best time for people with ALS to begin using a feeding tube, based on specific knowledge of each individual’s actual energy needs, rather than on general estimates of indicators such as bulbar function and weight change; and
  • design a clinical trial to test NIPPV prior to the onset of respiratory symptoms.

Vitamin E may protect against ALS

Data taken from more than a million people have revealed that those who take vitamin E supplements over a long period of time have a reduced risk of developing ALS.

Among the 1,055,546 trial subjects, whose data was culled from five non-ALS clinical trials conducted between 1976 and 2005, 805 developed ALS. Of those, information on vitamin E use was available for 231.

A research team at the Harvard School of Public Health in Boston published its findings online Feb. 18, 2011, in the American Journal of Epidemiology.

Although a straightforward examination of supplementation with vitamin E itself did not reveal any association with a higher or lower risk of ALS, a relationship between the duration of time for which people take the vitamin and ALS risk was observed.

People who take vitamin E for longer periods of time appear to have a lower relative risk of developing ALS than those who take the vitamin for shorter periods of time.

Compared with study subjects who didn’t take vitamin E:

  • there was no significant difference in the relative risk of developing ALS for those who took the supplement for one year or less;
  • participants who took vitamin E for a period of two to four years had about 25 percent less chance of getting the disease; and
  • those who supplemented their diets with vitamin E for five or more years had nearly 50 percent less chance of receiving a diagnosis of ALS.

An antioxidant, vitamin E helps protect against a cell-damaging process known as oxidative stress.

The results from a study led by neurologist Claude Desnuelle at CHU de Nice Hospital in France showed that vitamin E had no effect on survival or on the loss of muscle function in people with ALS who participated in a 2001 trial. Those who were taking it, however, were less likely to progress to severe ALS within the one-year study period.

Analysis of data gleaned from a 1982-1998 questionnaire-based study reported by Albert Ascherio, then an associate professor at the Harvard School of Public Health, and colleagues, also showed a relationship between vitamin E and ALS. Participants who reported taking vitamin E for 10 or more years had only 38 percent the risk of developing ALS than did non-vitamin E users. In those taking vitamin E for fewer than 10 years, the relative risk was 59 percent.

Note: Always consult with a physician before beginning a diet or supplement regimen.

Naltrexone: Benefits questionable, harm possible

An investigation has found no data to suggest that low-dose naltrexone might have a therapeutic effect in people with ALS. Furthermore, some data indicate the drug potentially may cause harmful effects, including liver toxicity.

Naltrexone was studied at the request of people with ALS who suggested it via the online forum ALSUntangled. The drug is approved by the U.S. Food and Drug Administration (FDA) for the treatment of addictions to alcohol or opiate drugs such as codeine and morphine.

The researchers, all members of the ALSUntangled forum, noted that some of naltrexone’s characteristics suggest that it may prove useful in immune system modification and neuroprotective strategies in ALS. However, “a small pilot study of a drug with similar mechanisms found no objective benefits.”

Additionally, the study team noted, a group of 31 people with ALS who participate in the online forum PatientsLikeMe obtained prescriptions for naltrexone from their physicians. Of the 31 patients who took the drug, 15 completed an evaluation of the treatment, with some reporting benefits that included decreased yawning, better balance, increased energy, improved speech and more effective breathing.

Seven participants (47 percent) said the drug had no effect or that they were unsure about whether it had.

Three participants (20 percent) reported “slight” efficacy, and four (27 percent) reported “moderate” benefits.

The full report detailing the new findings, “ALSUntangled No. 8: Low dose naltrexone for ALS,” was published in the January 2011 issue of Amyotrophic Lateral Sclerosis. The paper is available free online; put in search terms “ALSUntangled and naltrexone.”

Dozens of researchers worldwide participate in ALSUntangled discussions and investigations of new alternative and off-label therapies. (“Off-label” describes drugs prescribed to treat conditions other than the one[s] for which they were approved.)

The project was organized by the World Federation of Neurology in 2009 and is hosted on the organization’s ALS website.

(See Using Social Media to Advance ALS Research for a related article on social media and research in ALS).

Infection of G-CSF directly into the spinal cords of ALS mice helped the molecule confer far-reaching effects, including improved motor function and increased survival time.

Growth factor protects motor neurons in mice

Targeting and confining the experimental treatment G-CSF to the spinal cord improved motor function, delayed disease progression and increased survival time in mice with an ALS-like disease, a research team from Heidelberg, Germany, has reported.

The researchers, who published their findings in the February 2011 issue of Molecular Therapy, orchestrated the intraspinal delivery of G-CSF by encasing it in the emptied-out shell of an adeno-associated virus (AAV) and then injecting the construct directly into the spinal canal.

G-CSF (for Granulocyte-colony stimulating factor) belongs to a family of proteins called neurotrophic growth factors, which support the growth, health and survival of motor neurons.

Although previous studies have shown that the protein confers similar benefits when injected subcutaneously (under the skin) in ALS mice, complications have limited the systemic (whole-body) delivery necessary for the molecule to have more far-reaching effects.

The new findings show that in an ALS research model, G-CSF rescues motor neurons, improves conditions at the neuromuscular junction (the place where nerve cells meet muscle), and enhances regeneration of axons, the long fibers through which nerve cells conduct signals.

'NurOwn’ stem cell trial under way

Biotechnology company Brainstorm Cell Therapeutics is conducting a phase 1-2 clinical trial of stem cell therapy in adults with ALS.

The trial is designed to test Brainstorm’s experimental therapy NurOwn, and involves transplantation of multipotent mesenchymal stem cells secreting neurotrophic factors (MSC-NTF), into people with ALS. The cells are taken from each participant’s bone marrow and treated with NurOwn stem cell technology to create healthy NTF cells which, when transplanted back into the individual, are expected to produce and secrete neurotrophic factors essential for the survival and outgrowth of neurons.

The trial is being conducted at the Department of Neurology & Laboratory of Neuroimmunology, at the Hadassah Hebrew University Medical Center, Jerusalem, Israel, and is set to include 12 people with early-stage ALS and 12 people in more advanced stages of the disease.

In early-stage ALS trial subjects, MSC-NTF cells will be transplanted into patients’ clinically unaffected (or only mildly affected) upper arm biceps and triceps muscles. Each participant will receive 24 injections (under mild anesthesia) containing a total of 24 million cells.

In those subjects with more advanced ALS, transplantation of MSC-NTF cells will be made intrathecally (into the spinal canal) under mild anesthesia, via lumbar puncture. Each participant in this category will receive a total of 60 million cells.

The study is designed to establish safety of NurOwn first; later, investigators will look for signs of efficacy.

Brainstorm, with operations in New York and Petach Tikvah, Israel, was granted orphan drug designation for NurOwn by the U.S. Food and Drug Administration in February 2011. (Orphan drug status provides financial incentives for the development of drugs for rare diseases.)

For more information, visit and search for “NCT01051882.” Or, contact Dimitrios Karussis at +972-2-6776939, or; or Adi Vaknin-Dembinsky at +972-2-6776939, or; and refer to the study by its identifier.

Cyclosporin-based compound advances toward human trials

Maas Biolab of Albuquerque now has patent protection and orphan drug designation for its cyclosporine-based compound Mitogard.

Cyclosporin (sometimes spelled “cyclosporine”), an immunosuppressant, is believed to have neuroprotective properties.

Mitogard is designed to treat ALS and other neurodegenerative diseases by being infused directly into the cerebrospinal fluid, bypassing natural barriers that typically prevent penetration of the central nervous system.

Maas Biolab currently is conducting animal studies to assess the safety of the compound.

ALSN Staff
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