Application

Treatment of diabetic neuropathy using epigenetic modulators, histone deacetylase inhibitors (HDACis), to ameliorate or prevent vascular conditions and neuropathic pains by nerve damages.

Key Benefits

• Reverses or protects against diabetes-induced nerve damages by direct injection of HDACi.
• Relatively low regulatory risk because many HDACi candidates are at least partly tested in clinical trials for cancer applications.

Market Summary

Diabetic complications remain a serious public health issue. Diabetic neuropathy is the most common complication associated with diabetes mellitus, affecting about 50% of type 1 and 2 diabetes patients. HDAC inhibitors, a small molecular epigenetic regulator, have recently been explored to treat diabetic peripheral neuropathy. HDACis display pleiotropic activities, including the ability to restore defective gene expressions involved in cell cycle control, apoptosis, growth signaling, invasion/metastasis, angiogenesis and immune recognition. HDAC has been considered a promising target for cancer treatment as well as neuropathy.

Technical Summary

Emory researchers have identified new HDACi candidates for treatment of diabetic neuropathy. Schwann cells, DRG neurons, and endothelial cells, which are affected in diabetic neuropathy, were chosen to screen different types of HDACi under in vitro diabetic condition. FDA approved HDACi such as vorinostat and belinostat, as well as quisinostat were effective in clinical studies in increasing the repressed gene expression caused by diabetic conditioning. Among these HDACis, direct injection of belinostat improved nerve conduction velocity in diabetic animals. Also, belinostat ameliorated pains by touch (tactile allodynia) and prevented the decreased sensitivity to pain with heat (thermal hypoalgesia) which are the typical nerve damages associated with diabetes. Administration of belinostat increased blood vessel formation in diabetic nerves and showed protective effect on diabetes-induced nerve fiber loss in skins as well as ultrastructural morphology of myelinated fibers altered in diabetic nerves. Patients with diabetic neuropathy could be treated by direct HDACi injection restoring vascular and nerve functions.

Developmental Stage

In vitro and in vivo experiments have been performed.