Scientists Develop Vaccines Against ALS Mutations

Investigators in the laboratory of Jean-Pierre Julien at Laval University in Quebec have developed a new way to block abnormal SOD1 protein molecules, which cause SOD1-related amyotrophic lateral sclerosis (ALS) .

Although ALS resulting from a mutation in the SOD1 gene accounts for only about 1 percent to 3 percent of all ALS cases, it’s by far the best understood form of the disease, and the one on which most ALS mouse models are based.

In a paper published online Feb. 2 in Proceedings of the National Academy of Sciences, the scientists describe how they developed and tested vaccines against two types of SOD1 abnormalities.

First, they immunized a group of mice carrying a mutation known as G37R in their SOD1 genes by injecting them with abnormal SOD1 protein molecules along with a substance that stimulates the immune system.

Treated mice received three of these injections a few weeks apart, while a comparison (control) group received a salt solution with the immune system stimulant. The mice that received the SOD1 protein molecules lived an average of a month longer than those that got the salt injections.

However, when the scientists tried the same approach, but with a different type of abnormal SOD1 (the G93A mutation), in mice with extremely high levels of mutated SOD1 protein, the benefit was negligible.

They decided that, with this type of ALS-affected mouse, instead of trying “active” immunization, in which animals mount their own immune response, they would try a “passive” immunization approach, giving the mice ready-made immune system weapons known as antibodies, designed specifically to attack abnormal SOD1. They gave the antibodies directly into the nervous system, rather than injecting them under the skin.

The second approach prolonged the lives of the treated G93A mice by a week compared to a control group, and it significantly delayed the usual loss of body weight and impairment of leg function.

The researchers say the vaccination approach, especially a passive immunization based on specific antibody administration, “merits consideration” in patients with SOD1-related ALS. They note that such patients have much lower levels of mutated SOD1 protein than do the G93A mice used in these experiments.