The Practice of Experimental Neurotherapeutics in Neuromuscular Disease

PURPOSE OF REVIEW The discipline of experimental neurotherapeutics targets the process and operation of translating scientific discoveries into new treatments for neurologic diseases and has been instrumental in the progression of many areas of neurology.

RECENT FINDINGS From the US Food and Drug Administration (FDA) market approval of the first systemic in vivo gene therapy in neurology to multiple current gene-targeting therapeutics, monoclonal antibodies, and new drugs under development or approved in the last several years, the field of experimental neurotherapeutics has a presence in every neuromuscular clinic in the United States.

SUMMARY This article provides an overview of experimental neurotherapeutics with guidance on the clinical trials landscape, using examples in the field of neuromuscular disease. It covers the regulatory framework, clinical trial methodology, and offers advice on common pitfalls encountered when embarking on a clinical trials program in the clinic.

Address correspondence to Dr Lauren B Reoma, NIH/NINDS, 10 Center Dr, Bldg 10-2A23J, Bethesda, MD 20814, [email protected].

RELATIONSHIP DISCLOSURE: Dr Reoma has a noncompensated relationship as a Vice Chair of the American Academy of Neurology’s Experimental Neurotherapeutics Section and is the intramural National Institute of Neurological Disorders and Stroke (NINDS) program director for the NINDS-US Food and Drug Administration (FDA) fellowship in clinical trial methodology and regulatory science. Dr Griggs has received personal compensation in the range of $0 to $499 for serving on a scientific advisory or data safety monitoring board for Santhera Pharmaceuticals; in the range of $500 to $4999 for serving on a scientific advisory or data safety monitoring board for Idera, as an editor, associate editor, or editorial advisory board member for Lippincott, and as a study section member with the National Institutes of Health; in the range of $5000 to $9999 for serving as a consultant for Strongbridge Biopharma (now Xeris Pharmaceuticals, Inc) and on a data safety monitoring board for Solid Biosciences Inc; in the range of $10,000 to $49,999 for serving as an editor, associate editor, or editorial advisory board member for Elsevier. Dr Griggs has a noncompensated relationship as a member of the board of directors with the American Brain Foundation. The institution of Dr Griggs has received research support from the Muscular Dystrophy Association, the National Institutes of Health, the Parent Project Muscular Dystrophy, PTC Therapeutics, and Sarepta Therapeutics, Inc. Dr Nath has received personal compensation in the range of $10,000 to $49,999 for serving as an editor, associate editor, or editorial advisory board member for Elsevier. Dr Nath is the clinical director at the National institute for Neurological Disorders and Stroke (NINDS) and his research is supported by the ALS Association, NINDS, and the Office of AIDS Research at the National Institutes of Health.

UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE: Drs Reoma, Nath and Griggs discuss the unlabeled/investigational use of mexiletine for myotonic dystrophy, ketogenic diet for glycogen storage disease, and IL-6 cytokine inhibitor tocilizumab and JAK-STAT inhibitor ruxolitinib for the treatment of inflammatory myopathies.