ALS Research Briefs

NurOwn stem cell therapy trial set to begin

Biotechnology company Brainstorm Cell Therapeutics announced May 17, 2011, that it has received approval from Israel's Ministry of Health to conduct a phase 1-2 clinical trial of stem cell therapy in adults with ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease).

Brainstorm, with operations in New York and Petach Tikvah, Israel, will test its experimental therapy NurOwn in 12 people with advanced ALS, and in 12 who still are in the early stages of the disease. The study is designed to establish safety of NurOwn; future studies will look for signs of efficacy.

In a press release containing details about the experimental treatment and the trial, Adrian Harel, acting CEO of Brainstorm, said the company expects "to begin treating patients in the coming weeks."

Energy expenditure, eating and breathing 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 (TDEE) of people with ALS at different stages of the disease.

Further analysis of the initial findings (to be published in future reports) will enable the research team to:

  • develop two approaches for pinpointing the best time for a person with ALS to begin using a feeding tube (often called a PEG), 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 noninvasive positive pressure ventilation (NIPPV) prior to the onset of respiratory symptoms.

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, assisted ventilation 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).

Vitamin E may offer protective effect against ALS

Data taken from people more than a million people has 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 participants 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 their findings online Feb. 18, 2011, in the American Journal of Epidemiology.

Although supplementation with vitamin E in itself was not associated with ALS, the data did reveal an inverse relationship between the vitamin and the disease: 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 participants 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 years to four years were 77 percent as likely to get the disease; and
  • those who supplemented their diets with vitamin E for five or more years were 64 percent as likely to receive a diagnosis of ALS.

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

Results from a French study reported in 2001 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 questionnaire-based study that began in 1982 and ended in 1998 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 relative risk of developing ALS as compared to non-vitamin E users. Those taking vitamin E for fewer than 10 years had a 59 percent relative risk of developing ALS when compared to non-vitamin E users.

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

Growth factor protects motor neurons in ALS 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 team, which published its 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 nerve cells called 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 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) in an ALS model.

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 in humans 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 people, or 47 percent, said the drug had no effect or that they were unsure about any effect.
  • Three patients (20 percent) reported "slight" efficacy; and
  • Four people (27 percent) reported "moderate" benefits.

Dozens of researchers worldwide participate in ALSUntangled discussions and investigations of new alternative and off-label therapies. (Off-label describes drugs prescribed by physicians to treat conditions other than the one[s] for which the drugs received FDA approval.)

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

The full report detailing the new findings was published in the January 2011 issue of Amyotrophic Lateral Sclerosis, and is available for free to the public.

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