Better treatments for lipoatrophic diabetes: GLP-1 based drugs and leptin gene therapy

A particularly severe form of diabetes called lipoatrophic diabetes occurs in patients with lipodystrophy, where adipose tissue is limited or dysfunctional. The only specific treatment for lipodystrophy and lipoatrophic diabetes is replacement of the adipose hormone leptin. This requires painful daily injections and is extremely costly. Patients living with lipoatrophic diabetes consulted in the development of this application stated that a key need is “new treatments”. Glucagon like peptide-1 (GLP-1) drugs are highly effective treatments for type 2 diabetes. We discovered that short-term treatment with a GLP-1-based drug alleviated lipoatrophic diabetes in a preclinical model of lipodystrophy. Initial analyses of patients living with lipoatrophic diabetes show similar benefits, illustrating the translational potential of our findings. We also have exciting new data that single-injection gene therapy-based delivery of leptin drives long-lasting, dramatic reversal of liver disease in our preclinical lipodystrophy model. Uniquely, this project will define multisystem effects of longer-term treatment of lipoatrophic diabetes with the latest GLP-1 drugs and leptin gene therapy, alone and in combination. This could be translated rapidly to treatment of patients with the most appropriate GLP-1 drugs and underpin the development exciting new gene therapies such as leptin delivery to transform treatment of lipoatrophic diabetes.