Beneficial Therapy for ALS

Amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease) affects some 30,000 individuals in the United States with 5000 new cases diagnosed every year. It is a neurological condition characterized by progressive weakness of the muscles and is almost universally fatal. Although there are some treatments available like riluzole and adaravone that have achieved FDA approval, their effectiveness is restricted. As such, there is certainly a need to explore any and all possibilities that could cure or at least modify the time course of this devastating condition.

There is an animal model of ALS, a laboratory mouse, that is used in ALS research. And in this model significant benefit in terms of modifying the disease process has been demonstrated when these mice were given extremely high dosages of vitamin B 12. And because of vitamin B 12’s nurturing effects upon neurons, it certainly has been looked upon as a candidate for an ALS treatment.

As such, Japanese researchers set about to determine whether extremely high dosages or vitamin B 12 could help ALS patients. Their study, recently published in the Journal of the American Medical Association, utilized intramuscular administration of methyl cobalamin, a form of vitamin B 12, 50 mg, or placebo injected twice weekly for a 16-week period of time. The study enrolled 130 patients and they were randomized to either receive the vitamin B12 or placebo. Ultimately 126 of these patients completed the entire study.

At the completion of the 16-week period, the participants were evaluated on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS – R.) This is a standardized scale that evaluates change in functionality. Generally, ALS patients decline on this scale over time. So, the investigators used this scale to determine whether there was a change in the rate of decline in individuals receiving the high dosage B12 versus those who received placebo.

What the researchers found was quite remarkable.  Those receiving the high dosage B12 had a decline on the ALSFRS–R  score that was 45% less than patients who were on standard treatment like riluzole and received the placebo as seen below:

The authors speculated as to exactly how B 12 proved beneficial with respect to these patients. One thing we know and that they described is the fact that vitamin B 12 helps to reduce homocysteine. Homocysteine, as we have discussed previously, is neurotoxic. It induces damage to neurons as well as their mitochondria, and when elevated, helps increase inflammation that can lead to death of motor neurons. In fact, homocysteine levels are reported to be elevated patients with ALS.

In the 16-week study, the B 12 group seem to decline much less aggressively in comparison to those who did not receive it. All in all, the B 12 prove to be quite safe but again, this was only a four-month study. Here is the conclusion the authors reported:

“This phase 3 randomized clinical trial enrolling patients with early-stage ALS and moderate progression rate showed that ultrahigh-dose methylcobalamin significantly slowed clinical progression of the disease as assessed with the ALSFRS-R total score in the 16-week treatment period. The safety of ultrahigh-dose methylcobalamin for patients with ALS was also reproduced. “

As a neurologist, I can tell you that ALS is without question the most heart wrenching condition to deal with, especially in light of the fact that there is no significantly meaningful pharmaceutical treatment available as yet. For many years, we treated ALS with high dosage B 12, empirically. Empirically means basically as a guess. It seemed reasonable to use high dosage B 12 for reasons that are described above. Now, there’s been validation of this idea and it is certainly my hope that this information gets out aggressively to the ALS community.