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Immunomodulation of the Injury/Repair response of the CNS resident innate immune system as therapeutic approach for Amyotrophic Lateral Sclerosis


Despite the metabolic dysfunctions found in Amyotrophic Lateral Sclerosis (ALS) motoneurons, the uncontrolled Injury/Repair Microglia function seems to be the main responsible for the fast and fatal disease progression.

This immune dysfunction is reflected in the presence of reaction against the proteins of the spinal cord [1]. This immune reaction bears some similarity with the immune response observed during the relapse phase in patients with Chronic Progressive Multiple Sclerosis (CPMS).

Therefore, under compasive bases, we treated nine advanced ALS patients trying to improve their otherwise progressive invalidating and fatal condition with autologous T cell vaccination (TCV) similar to that used with CPMS patients.

Treated patients met the international accepted diagnosis criteria of ALS. They had between three and five years of evolution, but none of them needed mechanical respiratory assistance or had serious deglutory problems. Everyone presented the described immune alterations.

Doses of 5×108 inactivated specific T cells were administered every 28 days. 6/9 patients were immunized by IM injection, receiving a total of six doses each. 3/9 patients were immunized by IV infusion, receiving a total of three doses each.

The patients’ immune evaluation showed that the effector reaction diminished rhythmically and progressively during the first 6 to 24 months after vaccinations in 5/9 patients that experienced disease stability.

The progression of the disease stopped on 2/9 patients, which allowed them to reach a survival time of 14 and 16 years as of the time of diagnosis. In 3/9 the progression of the disease slowed down, resulting in death in 6 to 8 years as of the time of diagnosis. 4/9 patients died between 4 to 5 years as of the time of diagnosis. The median survival time from the disease onset, according to a Kaplan Meyer analysis, was 6 years.

The TCV treatment used seems to be an effective therapeutic approach to reestablish the lost control of this Injury/Repair Microglia function. Unfortunately this treatment failed to induce recovery of the lost neural function.


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