In a phase 1 study, infusions of expanded autologous regulatory T-lymphocytes (Tregs) in combination with subcutaneous IL-2 injections were safe and well-tolerated in three persons with ALS. Treg suppressive function was enhanced and disease progression stabilized during the periods of successive Treg infusions. In this study, the safety, tolerability and biological activity of Treg/IL-2 therapy was further assessed.
Seven participants were randomly assigned in a 1:1 ratio to receive either Treg infusions (1 x 10^6 cells/kg) intravenously every 4 weeks and IL-2 (2 x 10^5 IU/m^2) injections subcutaneously 3 times/week, or matching placebo infusions and injections in a 24-week randomized controlled trial (RCT). Six participants who successfully completed the RCT then proceeded into a 24-week dose-escalation open-label extension (OLE). Two additional participants entered directly into the OLE.
Treg/IL-2 treatments were safe and well-tolerated in the RCT and OLE. Treg suppressive function was higher in the active group of the RCT and during the OLE compared to baseline. Of the six participants who completed the RCT and OLE, three experienced minimal progression (2 active/1 placebo in the RCT), one showed intermediate progression (placebo) and two showed rapid progression (1 active/1 placebo) over 1 year. The two participants who entered directly into the OLE showed minimal to no progression over 6 months. The two participants with rapid progression had increased levels of two markers of peripheral inflammation (IL-17C and IL-17F) and two markers of oxidative stress (OLR1 and oxidized-LDL) compared to the other 6 participants.
This study demonstrates the promising approach of using Treg/IL-2 treatments to improve Treg suppressive function and slow the incessant disease progression in patients with ALS. (ClinicalTrials.gov number, NCT04055623).