Lloyd B. Klickstein
A physician-scientist who led the clinical studies at Novartis showing that low-dose mTOR inhibitors can boost immune function and cut infections in older adults.
Head of Translational Medicine, New Indications Discovery Unit, Novartis Institutes for BioMedical Research · MD, PhD
New Indications Discovery Unit, Novartis Institutes for BioMedical Research (Cambridge, Massachusetts, USA) ↗ ORCID0000-0002-4108-9123 ↗
Portrait: Springer Lab, Harvard Medical School
Lloyd Klickstein is a physician-scientist with MD and PhD degrees. According to a profile page, he is Head of Translational Medicine in the New Indications Discovery Unit at the Novartis Institutes for BioMedical Research. In 2018 he was the senior author of a clinical trial that asked whether blocking mTOR in a gentle way could help the aging immune system.
In that phase 2a trial, 264 older adults took a low dose of two mTOR inhibitors, BEZ235 and everolimus (RAD001), for 6 weeks. During the following year they reported fewer infections, their cells switched on more antiviral genes, and they responded better to a flu vaccine. The result made low-dose mTOR inhibition a serious idea for treating aging-related decline in immunity.
A later phase 3 trial of RTB101 (BEZ235) alone did not confirm a clinical benefit, so the 2018 result is best read as an encouraging first step that was not borne out in larger testing.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2014 | H | mTOR inhibition improves immune function in the elderly MAN2014 Older volunteers took the rapalog everolimus (RAD001) before a flu shot, and their antibody response to the vaccine rose by about 20% at doses that were fairly well tolerated. The share of T cells carrying the exhaustion marker PD-1 also fell. The PEARL authors summarise the doses as 0.5 mg daily or 5 mg weekly for 6 weeks. This is the human result behind the weekly low-dose idea. Boundary: a stronger vaccine response is a lab marker, not fewer infections, and the later RTB101 trial (MAN2021) shows how that gap can matter. |
| 2018 | H | TORC1 inhibition enhances immune function and reduces infections in the elderly MAN2018 Senior author of a phase 2a randomized trial (264 older adults) in which 6 weeks of low-dose BEZ235 plus everolimus was linked to fewer infections over the next year and a better flu-vaccine response. |
Co-authors in the Atlas 3
People with a profile here who share at least one study with Lloyd B. Klickstein.
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- David J. Glass 2 shared studies Muscle biologist and Regeneron vice president for ageing research, member of the US National Academy of Sciences, who helped discover the muscle-wasting enzymes MuRF1 and MAFbx and co-authored the first trials of low-dose mTOR inhibition in older people
- Joan B. Mannick 2 shared studies Ran early clinical trials of low-dose mTOR inhibitors in older adults, which improved their response to flu vaccination and, in a phase 2a trial, their rate of self-reported infections; a larger phase 3 trial of RTB101 (2021) did not confirm a reduction in respiratory illness. She led this work first at Novartis and then at resTORbio
- Dean Quinn Clinical trial investigator at P3 Research in Wellington, New Zealand, who was a co-author of the resTORbio trials that tested low-dose mTOR inhibitors to strengthen immunity in older adults
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