PT  - JOURNAL ARTICLE
AU  - Mannick, Joan B.
AU  - Morris, Melody
AU  - Hockey, Hans-Ulrich P.
AU  - Roma, Guglielmo
AU  - Beibel, Martin
AU  - Kulmatycki, Kenneth
AU  - Watkins, Mollie
AU  - Shavlakadze, Tea
AU  - Zhou, Weihua
AU  - Quinn, Dean
AU  - Glass, David J.
AU  - Klickstein, Lloyd B.
TI  - TORC1 inhibition as an immunotherapy to reduce infections in the elderly
AID  - 10.1101/230813
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 230813
4099  - http://biorxiv.org/content/early/2017/12/11/230813.short
4100  - http://biorxiv.org/content/early/2017/12/11/230813.full
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