Abstract

Objective: Assess the safety of Polyphenon E in subjects with multiple sclerosis (MS) and determine whether Polyphenon E would be futile as a neuroprotective agent.

Background Polyphenon E (Mitsui Norin; Shizuoka, Japan) is an extract from the leaves of green tea. Its main active component is epigallocatechin gallate (EGCG), an antioxidant that accumulates within the mitochondria of neurons and increases their resistance to apoptosis under conditions of oxidative stress. Mitochondrial dysfunction leads to axonal injury in mice with experimental autoimmune encephalomyelitis (EAE). EGCG effectively treats EAE in female SJL/J mice.

Design/Methods: Ten subjects with relapsing remitting or secondary progressive MS were recruited for this open-label, six-month pilot study of 400 mg of Polyphenon E twice daily. Adverse events (AE) were assessed monthly. N-acetyl aspartate (NAA) levels were measured using 3T magnetic resonance spectroscopy and differences were assessed between baseline and six-months. Plasma levels of epigallocatechin gallate (EGCG) were measured at one month, 3 and 8 hours after the morning dose.

Results: No serious AE occurred. All subjects completed the study assessments. One discontinued therapy after mild elevation of liver enzymes. Treatment with EGCG resulted in an increase of 13% [95%,CI(1%-23%) p<0.001] in average NAA levels. Free plasma levels of EGCG at 8 hours predicted changes in NAA; an increase in 10ng/ml in free EGCG levels resulted in a 6% [95%,CI(2%-10%)] increase in NAA.

Conclusions: There were no safety concerns for treating MS patients with Polyphenon E. Our futility endpoint was rejected, as NAA levels increased. This and the correlated changes in NAA and EGCG levels support a potential neuroprotective effect that should be investigated in a larger randomized, placebo-controlled trial measuring NAA levels over a longer follow-up.

Supported by: NCCAM K23AT004433; LSUHSC-New Orleans CTRC.

Disclosure: Dr. Ramos has nothing to disclose. Dr. Garrison has nothing to disclose. Dr. Koop has nothing to disclose. Dr. Rooney has nothing to disclose. Dr. Bourdette has received personal compensation for activities with Biogen Idec, Serono, and Teva Neurosciences as a speaker. Dr. Lovera has received personal compensation for activities with EMD Serono, Teva Neuroscience, and Biogen Idec as a consultant.