Amyotrophic Lateral Sclerosis

(ALS; also known as Lou Gehrig's Disease and Charcot’s Disease)

By Dr. Susanne Birnstiel

ALS is a condition in which motoneurons (nerve cells controlling motor functions) degenerate, leading to progressive paralysis. Since the disease only affects voluntary motor function, the patients stay perceptive and mentally sharp. Approximately 5,000 Americans are diagnosed with ALS each year. About 50% of ALS patients pass away within five years of diagnosis, frequently from complications concerning breathing. Other patients have been reported to survive for more than 10 years. The most prominent case is physicist Stephen Hawking.

Causes

For unknown reasons, motoneurons die off in ALS patients.

1) In about 5-10% of cases, there is a family history of ALS. Two of the genes associated with familial ALS have been identified, but these two genes are not sufficient to explain all the cases of familial ALS. Also, familial ALS frequently appears to be triggered by unknown environmental factors.

2) The vast majority of ALS cases is sporadic, meaning there is neither a family history of ALS nor any other apparent cause of the disease.

Symptoms and Diagnosis

ALS causes both muscle stiffness and weakness. Since similar symptoms are also observed in a multitude of other conditions and diseases, ALS is diagnosed by excluding all other possible conditions.

1) Early symptoms of ALS may consist of tripping, dropping items, slurred speech or muscle twinges. The clinical picture becomes clearer as muscle weakness and muscle stiffness progress.

2) The diagnostics frequently include an MRI of the brain, tests of neuromuscular conduction speeds, and samples of blood and spinal fluid, mainly to exclude other possible explanations for the symptoms.

3) The experience of a specialist who is seeing many ALS patients may help to make sure that the symptoms are caused by ALS and not by a similar condition requiring different treatment. Therefore, patients diagnosed with ALS are encouraged to get a second opinion.

Treatment

1) The only approved medication for ALS is riluzole (Rilutek®), which extends life expectancy by four to six months. Riluzole works by decreasing levels of glutamate, a brain chemical necessary for excitatory neural signaling that can lead to cell death when the concentration is too high.

2) Several neuro-protective drugs are currently in clinical trials.

3) Other treatments aim to ease the symptoms of patient, for example by physiotherapy, speech therapy, or breathing aids.

The search for a cure

Research on possible therapies is hampered by the problem that ALS cannot be attributed to a single cause. Replacing damaged neurons with stem cells still seems ideal but not feasible in the near future. However, there are some other current developments in ALS research:

1) Spinal motoneurons of patients with sporadic ALS produce a glutamate receptor that renders the neurons more vulnerable to toxic glutamate effects. Also, about 40% of patients with sporadic ALS have increased glutamate levels in their spinal fluid, and one of the transporters that keeps ambient glutamate levels low is frequently decreased in ALS patients. Data like these may lead to the development of more targeted medications.

2) It appears realistic at present to use stem cells to deliver protective substances to affected nerves.

3) Protective mechanisms and/or blockers of damaging mechanisms could also be loaded into a harmless virus and injected into a muscle. Ailing nerves have been shown to take up the virus and “infect” themselves with their medication.

These and other exciting breakthroughs will, hopefully, soon migrate from the laboratory to the hospital, to the benefit of the patient. For current clinical trials, visit www.clinicaltrials.gov and talk to your physician.