Experimental Drug Prevents Nerve Damage in Diabetic Mouse Model

An experimental low molecular drug has been shown to protect mice from developing diabetic peripheral neuropathy (DPN), a condition of nerve degeneration that can lead to amputation of limbs in diabetes patients.

Investigators at the University of Kansas (Lawrence, USA) studied the effect of the novobiocin-based experimental drug KU-32, which is a C-terminal inhibitor of the master heat-shock protein Hsp90. Inhibition of Hsp90 causes an increase in the production of a different heat shock protein, Hsp70, which is known to protect against DPN.

Two groups of mice, normal controls (WT) and Hsp70 "knock-out” mice (genetically engineered to lack the gene for Hsp70), were rendered diabetic with streptozotocin for 12 weeks. After 12 weeks of diabetes, both WT and Hsp70 knockout mice developed deficits in nerve conduction velocity (NCV) and a sensory hypoalgesia. The two groups of animals were then treated with KU-32.

Results published in the July 14, 2010, online edition of the journal ASN Neuro revealed that although KU-32 did not improve glucose levels, HbA1c (glycated hemoglobin) or insulin levels, it reversed the NCV and sensory deficits in WT but not Hsp70 knock-out mice. During the study, KU-32 appeared to be completely nontoxic and was readily absorbed from the blood stream.

"People with DPN can be very sensitive to light touch, which can cause significant pain,” said senior author Dr. Rick Dobrowsky, professor of pharmacology and toxicology at the University of Kansas. "The other side is eventually diabetes causes death of the nerves. DPN often leads to loss of feeling in the hands and feet, which can make diabetics susceptible to wounds and infections and often leads to amputations of toes and feet.”

"The idea is to try to determine at what point in nerve degeneration will be most effective and at what point the drug will not be efficacious,” said Dr. Dobrowsky. "We would like to know at what stage in the progression of DPN a window of opportunity exists for the beneficial use of KU-32.”

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