Expanded autologous regulatory T-lymphocyte infusions in ALS A phase I, first-in-human study

Jason R. Thonhoff, David R. Beers, Weihua Zhao, Milvia Pleitez, Ericka P. Simpson, James D. Berry, Merit E. Cudkowicz, Stanley H. Appel

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


Objective To determine whether autologous infusions of expanded regulatory T lymphoctyes (Tregs) into patients with amyotrophic lateral sclerosis (ALS) are safe and tolerable during early and later stages of disease. Methods Three patients with ALS, with no family history of ALS, were selected based on their differing sites of disease onset and rates of progression. Patients underwent leukapheresis, and Tregs were subsequently isolated and expanded ex vivo. Tregs (1 106 cells/kg) were administered IV at early stages (4 doses over 2 months) and later stages (4 doses over 4 months) of disease. Concomitant interleukin-2 (2 105 IU/m2/injection) was administered subcutaneously 3 times weekly over the entire study period. Patients were closely monitored for adverse effects and changes in disease progression rates. Treg numbers and suppressive function were assayed during and following each round of Treg infusions. Results Infusions of Tregs were safe and well tolerated in all patients. Treg numbers and suppressive function increased after each infusion. The infusions slowed progression rates during early and later stages of disease. Spearman correlation analyses showed that increased Treg suppressive function correlated with slowing of disease progression per the Appel ALS scale for each patient: patient 1: ? (rho) = -0.60, p = 0.003; patient 2: ? = -0.71, p = 0.0026; and patient 3: ? = -0.54, p = 0.016. Measures of maximal inspiratory pressure also stabilized, particularly in 2 patients, during Treg infusions. Conclusions These results demonstrate the safety and potential benefit of expanded autologous Treg infusions, warranting further clinical trials in patients with ALS. The correlation between Treg suppressive function and disease progression underscores the significance of using Treg suppressive function as an indicator of clinical status.

Original languageEnglish (US)
Article numbere465
Pages (from-to)e465
JournalNeurology: Neuroimmunology and NeuroInflammation
Issue number4
StatePublished - Jul 1 2018

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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