Lipodystrophy Patients Helped with Innovative Leptin Therapy

Dr. Elif Oral

(May 22, 2009) Dr. Elif Oral, M.D., Assistant Professor in the Metabolism, Endocrinology & Diabetes Division, has recently begun treating lipodystrophy patients with recombinant human leptin therapy, making the University of Michigan the third medical center in the U.S. (and only the fourth in the world) to do so. Lipodystrophy is a rare metabolic disorder resulting in total or partial loss of body fat, abnormalities in carbohydrate and lipid metabolism, immune system dysfunction, and severe resistance to insulin.

Under a Clinical Trial Agreement with Amylin Phramaceuticals (San Diego, CA), Dr. Oral began treating two Michigan patients with the novel therapy in April. A nine-year-old girl with rare, autoimmune-caused lipodystrophy and a young woman with genetic partial lipodystrophy are already seeing significant improvements. The metreleptin is injected twice daily at the beginning and may be switched to once a day if the patient is stable after about six months.

In 1997, Dr. Oral was one of several researchers who became interested in the idea of supplying the missing fat cell hormone (leptin) in lipodystrophy patients, similar to how insulin is replaced in type 1 diabetes patients. This novel therapy was proven extremely successful in animals by researchers at the University of Texas Southwestern Medical Center in 1999. In 2001–2002, while working at the National Institutes of Health, Dr. Oral was able to treat nine human patients, who experienced dramatic recoveries (New England Journal of Medicine 2002 Feb 21; 346(8):570-8).

Since transferring to the University of Michigan in 2002, Dr. Oral has worked on setting up a new leptin trial to continue her research. She is now actively recruiting patients to participate in the study. Patients with the clinical diagnosis of lipodystrophy and one metabolic abnormality (diabetes mellitus and/or hypertriglyceridemia) are being sought. Patients who have high triglycerides and require hundreds of units of insulin may also qualify for the study, if they clinically display partial lipodystrophy.

Patients on thousands of units of insulin have been able to come off insulin completely while being maintained on leptin. In other cases, patients on leptin therapy can go to much lower insulin doses. "Those with generalized or complete lipodystrophy may only live into their 20s or early 30s, so this therapy offers great hope to improve their lifespan,” explains Dr. Oral. "It is so wonderful to see magic results for these patients. As a doctor and a researcher, you live for that!”

Lipidystrophy is a rare disease and this novel therapy is only being offered at the U-M, the NIH, UT Southwestern (Dallas, Texas), and Osaka, Japan. Dr. Oral welcomes her colleagues' help in finding more patients by notifying physicians in the fields of endocrinology, genetics, and pediatrics about the clinical trial.

The clinical trial is listed on the Engage website as HUM00021139, "Lipodystropy Research with Metreleptin, an Investigational Study Medication." Dr. Elif Oral may also be contacted at (734) 615-7271 or eliforal@umich.edu or through her study coordinator, Adam Neidert, at (734) 615-0539 or aneidert@umich.edu.