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Thonhoff JR, Beers DR, Zhao W, et al. Expanded autologous regulatory T-lymphocyte infusions in ALS: A phase I, first-in-human study. Neurol Neuroimmunol Neuroinflamm. 2018;5(4):e465doi: 10.1212/NXI.0000000000000465.
Thonhoff, J. R., Beers, D. R., Zhao, W., Pleitez, M., Simpson, E. P., Berry, J. D., Cudkowicz, M. E., & Appel, S. H. (2018). Expanded autologous regulatory T-lymphocyte infusions in ALS: A phase I, first-in-human study. Neurology(R) neuroimmunology & neuroinflammation, 5(4), e465. https://doi.org/10.1212/NXI.0000000000000465
Thonhoff, Jason R, et al. "Expanded autologous regulatory T-lymphocyte infusions in ALS: A phase I, first-in-human study." Neurology(R) neuroimmunology & neuroinflammation vol. 5,4 (2018): e465. doi: https://doi.org/10.1212/NXI.0000000000000465
Thonhoff JR, Beers DR, Zhao W, Pleitez M, Simpson EP, Berry JD, Cudkowicz ME, Appel SH. Expanded autologous regulatory T-lymphocyte infusions in ALS: A phase I, first-in-human study. Neurol Neuroimmunol Neuroinflamm. 2018 May 18;5(4):e465. doi: 10.1212/NXI.0000000000000465. eCollection 2018 Jul. PMID: 29845093; PMCID: PMC5961523.
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Neurol Neuroimmunol Neuroinflamm. 2018 May 18;5(4):e465. doi: 10.1212/NXI.0000000000000465. eCollection 2018 Jul.

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

Neurology(R) neuroimmunology & neuroinflammation

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

Affiliations

  1. Houston Methodist Neurological Institute (J.R.T., D.R.B., W.Z., M.P., E.P.S., S.H.A.), Houston Methodist Hospital Research Institute, Stanley H. Appel Department of Neurology, Houston, TX; and Neurological Clinical Research Institute (J.D.B., M.E.C.), Massachusetts General Hospital, Boston, MA.

PMID: 29845093 PMCID: PMC5961523 DOI: 10.1212/NXI.0000000000000465

Abstract

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 × 10

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: ρ (rho) = -0.60,

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.

CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence. This is a phase I trial with no controls.

References

  1. JCI Insight. 2017 Mar 9;2(5):e89530 - PubMed
  2. Brain. 1995 Jun;118 ( Pt 3):707-19 - PubMed
  3. Cytotherapy. 2016 Oct;18(10 ):1312-24 - PubMed
  4. Neurobiol Dis. 2012 Dec;48(3):418-28 - PubMed
  5. Nat Immunol. 2005 Apr;6(4):345-52 - PubMed
  6. Sci Transl Med. 2015 Nov 25;7(315 ):315ra189 - PubMed
  7. EMBO Mol Med. 2013 Jan;5(1):64-79 - PubMed
  8. Neurology. 2008 Oct 21;71(17):1326-34 - PubMed
  9. Immunology. 2006 Mar;117(3):289-300 - PubMed
  10. Brain. 2011 May;134(Pt 5):1293-314 - PubMed
  11. J Exp Med. 2004 Apr 5;199(7):971-9 - PubMed

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