RT Journal Article
SR Electronic
T1 TORC1 inhibition as an immunotherapy to reduce infections in the elderly
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 230813
DO 10.1101/230813
A1 Joan B. Mannick
A1 Melody Morris
A1 Hans-Ulrich P. Hockey
A1 Guglielmo Roma
A1 Martin Beibel
A1 Kenneth Kulmatycki
A1 Mollie Watkins
A1 Tea Shavlakadze
A1 Weihua Zhou
A1 Dean Quinn
A1 David J. Glass
A1 Lloyd B. Klickstein
YR 2017
UL http://biorxiv.org/content/early/2017/12/11/230813.abstract
AB mTOR inhibition extends lifespan and ameliorates aging-related pathologies including declining immune function in model organisms. The objective of this Phase 2a clinical trial was to determine if low dose mTOR inhibitor therapy enhanced immune function and thereby decreased infection rates in elderly subjects. The results indicate that 6 weeks of treatment with a low dose combination of a catalytic (BEZ235) plus an allosteric (RAD001) mTOR inhibitor (that selectively inhibits TORC1 downstream of mTOR) was safe, significantly decreased the rate of infections reported by elderly subjects for a year following study drug initiation, upregulated antiviral gene expression, and significantly improved influenza vaccination response. Thus selective TORC1 inhibition with a combination of BEZ235 and RAD001 may be efficacious as immunotherapy to reduce infections, a leading cause of death in the elderly.One Sentence Summary Treatment of elderly subjects with a low dose mTOR inhibitor regimen that selectively inhibits TORC1 significantly decreased infection rates