February 2, 2006

International ALS Meeting Covers
Research, Care and Goals

Dr. Valerie Cwik, MDA’s medical director and a neurologist who formerly directed the MDA/ALS Center in Tucson, Ariz., attended the 16th International Symposium on ALS/MND in Dublin, Ireland, in December.

The meeting was sponsored by the British Motor Neurone Disease Association, in cooperation with the International Alliance of ALS/MND Associations. This year’s conference was attended by some 900 neurologists, basic scientists and allied health professionals.

Here’s Dr. Cwik’s report.

Clinical Trials Results

Results of several clinical trials were presented. A summary follows.

  • AEOL 10150, a potent antioxidant made by Aeolus Pharmaceuticals that targets dangerous byproducts of cellular metabolism, was reported to be safe and well tolerated by ALS patients at a variety of dosage levels. Robert Miller, director of the MDA/ALS Center in San Francisco, reported the results and said a larger trial is planned.

  • Glatiramer acetate (Copaxone), a drug used in the treatment of multiple sclerosis that may boost production of cells that suppress the immune system, was reported to be safe and well tolerated in ALS patients in a clinical trial involving some 30 participants. Paul Gordon, co-director of the MDA/ALS Center at Columbia University in New York, announced the results. Further studies are planned.

  • TCH346, a small molecule developed by Novartis, designed to block the cell death pathway, failed to demonstrate a beneficial effect on disease progression. The trial included some 500 ALS patients, divided into groups taking four different dosage levels of TCH346 and a placebo (inert substance) group.

  • A nine-month study of creatine in some 100 ALS patients also failed to show benefit, confirming the negative findings of two previous creatine studies in ALS. The trial was coordinated by Jeffrey Rosenfeld, director of the MDA/ALS Center in Charlotte, N.C.


Clinical Trial Design

Several presentations focused on the design and conduct of clinical trials in ALS. Clinical trials in this disease typically require large number of patients, a relatively long duration, and are expensive. New designs to address these issues were discussed. Briefly, these included

  • so-called inferiority/superiority study designs to rapidly screen therapies in relatively small numbers of patients and either exclude a treatment from further testing or recommend it for a larger study

  • studies using patients with rapidly progressing ALS

  • studies that compare the rate of progression of a patient’s disease before and after an experimental treatment instead of comparing a treated group of patients to an untreated (control) group


Studies in ALS Genetics and Epidemiology (Disease Patterns)

A number of speakers addressed genetic and epidemiologic issues in ALS.

  • Christen Shoesmith, an MDA grantee at the University of Western Ontario, presented the results of a study showing that about 2 percent of ALS patients have respiratory impairment as their first disease symptom, that this pattern is more common in males, and that it does not necessarily mean the disease will progress faster.

  • There appears to be a reduced incidence of ALS among African-Americans and among immigrants to the United Kingdom from the Indian subcontinent, the Caribbean and Africa compared to other ethnic groups.

  • Smoking did not appear to be a risk factor for ALS in a study from Australia.

  • Genetic susceptibility to certain viruses or toxins may underlie some cases of ALS.

  • Hiroshi Mitsumoto, who co-directs the MDA/ALS Center at Columbia University in New York, presented results of his MDA-funded work to develop a structured interview on which to base a study of potential genetic and environmental risk factors for ALS. Some items in the interview questionnaire have been revised from their original form. Telephone interviews appear to be as reliable as face-to-face interviews, simplifying the research process.


Current Treatments

Some sessions focused on currently available treatments. Among these were presentations on

  • advances in gastrostomy (feeding) tube placement and care, including 1) a new mask that allows for simultaneous noninvasive ventilation and g-tube placement, reducing the risk of respiratory complications during tube insertion and 2) a method of placing gastrostomy tubes without sedation and with only local anesthesia, reducing risks for the ALS patient

  • approaches to respiratory care, including 1) increasing lung capacity through breath stacking 2) the use of manually or mechanically assisted coughing to handle mucus buildup and 3) the use of a vibrating vest to assist in getting rid of mucus buildup, a technique that was met with skepticism by the conferees


Caring for Caregivers

Several presentations highlighted the need to attend to the needs of caregivers of ALS patients, as well as the patients themselves. When the patient is cognitively impaired, the negative impact on the caregiver is greater, the presenters said.


Basic Science Research

Several studies in cells and animal models of ALS were presented. A summary of findings follows.

  • A newly identified compound called angiogenin, which is produced in the nervous system, was found to protect nerve cells (neurons) in laboratory dishes from certain types of injury.

  • In mice with an ALS-causing mutation in a gene known as SOD1, a combination of exercise and insulin-like growth factor 1 (IGF1) nearly doubled survival time.

  • Compounds called antisense oligonucleotides can reduce levels of abnormal SOD1 protein in rats with an ALS-causing mutation in the SOD1 gene. Treatment with these compounds did not delay the onset of ALS, but it did modestly extend survival. Further studies are under way to develop antisense therapy as a possible treatment for familial ALS related to the SOD1 gene.


Recognition of MDA Grantee

Stanley Appel, a long-time MDA research grantee and director of the MDA/ALS Center at Methodist Hospital in Houston, was given the Forbes Norris Award for exceptional care and compassion in the study and management of ALS. Appel’s current work focuses on the role of the immune system and inflammatory processes in ALS.


Toward the Future

At a meeting of the ALS Research Group, formed at an MDA-sponsored conference on ALS held in 2003 in Tarrytown, N.Y., an ALS DNA banking project, to be funded mostly by the National Institutes of Health, was discussed. The researchers hope to store DNA from some 2,000 blood samples taken from people with and without ALS.

At the inaugural meeting of MDA’s new ALS Translational Research Advisory Committee (TRAC), Stan Appel, meeting chairman, encouraged discussion of the committee’s goals. Like MDA’s general TRAC, the ALS TRAC will help promising research move from the laboratory to clinical trials in as short a time as possible. Sharon Hesterlee, MDA’s research development director, will work with him to plan the next steps.