From hormone to pharmaceutical: lipodystrophy

2000

Challenge

Lipodystrophy is a rare disease in which patients lack body fat and fat-derived hormones, such as leptin. Generalized lipodystrophy results in extreme forms of diabetes, insulin resistance, triglyceride elevation, and fatty liver disease, all of which complicate treatment and can lead to significant morbidity and mortality.

Advance

The first fat-derived hormone, leptin, was discovered in 1994. Since 2000, IRP researchers from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), including Phillip Gorden, M.D., and Rebecca J. Brown, M.D., M.H.Sc., have treated more than 100 lipodystrophy patients with leptin replacement therapy, resulting in dramatic improvements in diabetes, lipid levels, and quality of life.

Impact

Based on these clinical studies, metreleptin (Myalept), the first recombinant leptin analog, was approved by the FDA in 2014 to treat patients with generalized lipodystrophy. Targeted treatment of leptin deficiency in lipodystrophy represents a major medical advance in the treatment of an unusual and otherwise difficult-to-treat disease.

Publications

Oral EA, Simha V, Ruiz E, Andewelt A, Premkumar A, Snell P, Wagner AJ, DePaoli AM, Reitman ML, Taylor SI, Gorden P, Garg A. (2002). Leptin-replacement therapy for lipodystrophy. N Engl J Med. 346(8), 570-8.

Chong AY, Lupsa BC, Cochran EK, Gorden P. (2010). Efficacy of leptin therapy in the different forms of human lipodystrophy. Diabetologia. 53(1), 27-35.

Chan JL, Lutz K, Cochran E, Huang W, Peters Y, Weyer C, Gorden P. (2011). Clinical effects of long-term metreleptin treatment in patients with lipodystrophy. Endocr Pract. 17(6), 922-32.

Gorden P, Zadeh ES, Cochran E, Brown RJ. (2012). Syndromic insulin resistance: models for the therapeutic basis of the metabolic syndrome and other targets of insulin resistance. Endocr Pract. 18(5), 763-71.