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Infusions of Regulatory T Cells Slowed ALS Progression in First-in-Humans Trial

Key findings

  • Increased Treg suppressive function correlated with slowing of disease progression
  • In the first-in-human study, autologous infusions of regulatory T cells (Tregs) were safe and well tolerated by three ALS patients regardless of burden of disease
  • The infusions slowed ALS progression during both early and later stages of disease
  • Treg infusions did not adversely affect respiratory function and in fact appeared to stabilize a decline in maximal inspiratory pressures in two patients

It has been shown in mice that regulatory T cells (Tregs) infusions, which are immunosuppressive, slow the progression of amyotrophic lateral sclerosis (ALS) and prolong survival. Now, the first-in-human phase 1 trial has demonstrated that infusions of Tregs also slow ALS progression in human patients. The study was published in Neurology: Neuroimmunology & Neuroinflammation.

James D. Berry, MD, a neurologist, and Merit E. Cudkowicz, MD, chief of the Neurology Service and director of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, and colleagues set out simply to evaluate the safety and tolerability of the infusions. They enrolled three patients at the Houston Methodist Neurological Institute who had different sites of symptom onset and different rates of disease progression between January 2016 and February 2018.

As part of the study, patients underwent leukapheresis one month before the first Treg infusion. Each patient's Tregs were separated from white blood cells and increased in number and then administered back into the patient intravenously. To stabilize the infused Tregs and possibly enhance their suppressive function, the researchers concomitantly injected the patients with low-dose interleukin-2 (IL-2).

Each patient received eight Treg infusions. In the first round, four infusions were given two weeks apart; in the second round, four infusions were given one month apart. Patient one had the first infusion 14 months after symptom onset, and patient two at 24 months and patient three at 38 months.

In all patients, the number of Tregs and their suppressive function increased during the first round of infusions, declined between the two rounds then increased again during the second round.

Safety Results

  • During each round of infusions, all patients noted "dramatic" increases in the frequency, intensity and distribution of fasciculations, starting a few minutes to a few days after each infusion and lasting from days to more than one month after the completion of each round
  • Patient one reported increased muscle cramps in his legs (weeks two to six), two falls (weeks 17 and 23) and an episode of pharyngitis (week 10)
  • Patient two experienced progressive dysphagia and an episode of aspiration pneumonia, which were attributed to bulbar ALS. He withdrew from the study during week 50 due to progressive disease and died during week 51
  • Patient three developed two suspected gastrointestinal infections and an upper respiratory infection between weeks 24 and 29. She reported mild dyspnea on exertion that began during week 48
  • There were no infusion-related adverse events or clinically significant changes in laboratory test results or electrocardiography

The potential for an increased risk of infections with Tregs and IL-2 treatment is a concern and needs to be investigated in larger studies, the researchers say.

In all patients, the rate of disease progression, measured with the ALS Functional Rating Scale–Revised (ALSFRS–R) and the Appel ALS Rating Scale (AALS), slowed for two months during the first round of infusions, accelerated between each round of infusions and slowed again over four months during the second round.

Moreover, they found the larger the increase in Treg suppressive function, the smaller the amount of disease progression at the next visit.

In patients one and three, maximal inspiratory pressures (MIPs) were stable during the first round of infusions, deteriorated between rounds and stabilized during the second round. In patient two who was receiving noninvasive ventilation, MIPs were low but remained relatively stable. In all patients, forced vital capacity remained relatively unchanged.

The research team is planning a randomized, placebo-controlled phase 2 study of Treg infusions in a larger number of patients, over a longer period and at regular intervals.

Learn more about Neurology at Mass General

Learn more about Mass General Neuroscience


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