Treg Study: Therapeutic Goal – To Increase Neuroprotective FoxP3 Tregs in ALS Patients

Research Summary

Principle Investigator: Stanley Appel MD

This study may lead to Treg cell therapy for symptom management or potential slowing of disease progression in ALS and related disorders. This study is to isolate T regulatory (Treg) cells from the blood using leukapheresis, and expand T regulatory (Treg) cells in the laboratory in up to twelve patients with ALS. Leukapheresis is a laboratory procedure in which white blood cells are separated from a sample of blood. Once separated, the remainder of the blood is returned to the circulation. The subject’s Treg cells will be grown (manufactured) in a specialized GMP laboratory facility, tested and purified. The subject’s own expanded Treg cells will then be injected into the skin with or without the addition of IL-2 (Interleukin-2). As of 4/22/15, the following has been achieved:

  1. Peripheral blood monocytes (PBMC) have been removed from 4 ALS patients and 3 healthy controls.
  2. Treg lymphocytes have been isolated from the PBMC by affinity columns
  3. Treg lymphocytes have been expanded with anti-CD3 and anti-28 beads, in the presence of IL-2 and rapamycin.
  4. Function of the isolated Tregs: The ability of the isolated Tregs to suppress the proliferation of Teffector lymphocytes has been assessed before expansion and following several cycles of expansion.
  5. Tregs freshly isolated from ALS patients have no functional activity, i.e., they cannot suppress proliferation of Teffector cells. However, after 1–2 cycles of expansion the ALS Tregs revert to their normal function and are equivalent to Tregs isolated from healthy controls. The expanded Tregs from ALS patients also suppress the secretion of pro-inflammatory cytokines.
  6. The last step prior to submission of our IND is under way – namely to freeze aliquots of PBMC, and then thaw at different times to simulate the process to be employed – namely, infusion of the expanded Treg q 3 weeks.


Massachusetts General Hospital
Merit Cudkowicz MD
James Berry MD

Houston Methodist Neurological Institute
Stanley Appel MD