JOT108 Alzheimer's Disease

• ​Positive resveratrol outcomes in Alzheimer’s Disease (AD) has fueled interest due to failures in multiple anti-amyloid trials.​
• The multifunctional Mechanism Of Action of high plasma levels of resveratrol is shown to benefit reduction of inflammation, Mitochondria (fuel to the cells), oxidative stress and prevent neurodegeneration.
• In a 119 patient Phase 2 AD study (performed by Georgetown University), resveratrol demonstrated stabilization of key biomarkers.
  • Compared to the placebo-treated group, at 52 weeks, resveratrol markedly reduced CSF MMP9 and increased macrophage-derived chemokine (MDC), interleukin (IL)-4, and fibroblast growth factor (FGF)-2.
  • Compared to baseline, resveratrol increased plasma MMP10 and decreased IL-12P40, IL12P70, and RANTES. In this subset analysis, resveratrol treatment attenuated declines in mini-mental status examination (MMSE) scores, change in ADL (ADCS-ADL) scores, and CSF Aβ42 levels during the 52-week trial, but did not alter tau levels.
  • Conclusions: Collectively, these data suggest, while using an insufficient threshold dose of unformulated resveratrol, that resveratrol decreases CSF MMP9, modulates neuro-inflammation, and induces adaptive immunity. Trial registration: ClinicalTrials.govNCT01504854
• Based on other positive resveratrol neurological studies with a pharmacokinetic component (4), the highest dose administered in treating AD patients did not generate the plasma levels of resveratrol that the investigators and JOT believes is needed for full therapeutic effect of resveratrol, which can be achieved through JOTROL administration.

1. Turner RS et al, A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer’s disease, Neurology 2015 Oct 20;85(16):1383-91. doi: 10.1212/WNL.0000000000002035. PMID 26362286.
2. Moussa C et al, Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease. J Neuroinflammation. 2017 Jan 3;14(1):1. doi: 10.1186/s12974-016-0779-0. PMID: 28086917. (Selected as Editor’s Choice: Martin I: Resveratrol for Alzheimer’s disease. Science Translational Medicine. 2017 Feb;9:375).
3. SawdaC et al, Ann NY AcadSci. 2017 Sep;1403(1):142-149. doi: 10.1111/nyas.13431. Epub2017 Aug 16. PMID 28815614.
4. YiuEM et al, J Neurol. 2015 May;262(5):1344-53. doi: 10.1007/s00415-015-7719-2. Epub2015 Apr 7.