Lipoic acid as an immune modulator in multiple sclerosis

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DESCRIPTION (provided by applicant): Vijayshree Yadav, MD seeks funding for a Mentored Patient Oriented Research Career Development Award to obtain the skills necessary to design and conduct scientifically rigorous clinical trials. Dr Yadav is a board certified neurologist who has completed her fellowship in Neuroimmunology. Her career goal is to become an independent clinical investigator. The plans for achieving these objectives include obtaining a master's degree in clinical research (MCR) and successfully conducting a phase I clinical trial in multiple sclerosis (MS). The MCR course is offered as part of Human Investigations Program (HIP) at OHSU that is sponsored by NIH. Dr Yadav will conduct a 24-week double blind placebo controlled study using oral lipoic Acid (LA) in MS. LA has been shown to be effective in treating and suppressing experimental autoimmune encephalomyelitis (EAE) in mice, a disease model for MS. There is preliminary data from the EAE studies as well as from a pilot study in MS patients done by Dr Yadav and her mentor Dr Dennis Bourdette suggesting significant immunological effects upon use of LA. The proposed study is designed primarily to assess the immunological effects of 24-week of administration of LA in MS patients. The primary goal of the study will be to assess effects of LA on putative biomarkers in MS such as adhesion molecules and matrix metalloproteinase-9 along with other inflammatory markers. The secondary outcomes will include assessment of safety of high dose LA administration and potential clinical benefits from 24 weeks of LA use. The study will also include pharmacokinetic study of LA. Sixty MS subjects with relapsing remitting form of MS will be randomized to placebo or 1200 mg twice a day of LA. The study will be conducted at the General Clinical Research Center at the OHSU. This study will help in exploring oral LA as potential treatment for MS. The study is relevant as the present treatment options for MS have significant limitations such as being only partially effective, available only in injectable forms, with significant side effects and very costly. This application proposes a structured didactic training program for Dr Yadav to ensure her independence as a clinical investigator at the end of the 5 year award period.