Amyotrophic lateral sclerosis (ALS) is a highly progressive, fatal neurodegenerative disorder that was first identified in 1869. A cure for ALS has so far eluded researchers and current therapy only offers symptomatic management. Findings from a recent phase I trial, published Neurology: Neuroimmunology & Neuroinflammation, have opened up a new avenue for the treatment of ALS.

Led by Stanley H. Appel, MD, Peggy & Gary Edwards Distinguished Endowed Chair in the Stanley H. Appel Department of Neurology and co-director of the Houston Methodist Neurological Institute, the trial results showed that the new immunotherapy treatment was safe and well tolerated by ALS patients.

Prior preclinical studies conducted by Appel and researchers Jenny Henkel, PhD, and David Beers, PhD, revealed that regulatory T lymphocytes (Tregs) suppressed disease progression in ALS murine models, leading them to investigate Treg levels in patients. "We found that many of our ALS patients not only had low levels of Tregs, but also demonstrated impaired Treg function. This opened up the tantalizing possibility of providing therapeutic benefit by increasing the number and function of Tregs," Appel said.

In the phase I trial, Tregs from three patients at different stages of ALS were isolated and expanded ex vivo. Interestingly, the team found that Tregs with impaired suppressive function in ALS patients functioned normally once expanded outside the body. Each patient received eight Treg infusions with concomitant interleukin-2 injections.

According to lead author Jason Thonhoff, MD, PhD, each dose of Tregs resulted in a 30 to 40 percent increase over normal levels. Slowing of disease progression was observed during every round of infusion. "We are currently bound by therapy that only offers symptomatic management for patients, so I am very excited by the promise that these findings show," said Thonhoff.

The goal of the phase I trial was to determine if it was safe to increase the levels of functioning Tregs in ALS patients. "As we expected, our results showed it was safe to increase Treg levels and all patients tolerated the infusion very well," Appel noted. "What surprised us was that the disease progression dramatically slowed during infusions, but then rapidly increased following cessation." Phase II, randomized, placebo-controlled trials are needed to test clinical efficacy, safety and tolerability of different doses of Tregs in a larger number of patients.

Read the full paper here.