Anti-diabetic Drug Slows Parkinson’s Disease Progression

Glibenclamide, the anti-diabetic medication was found to slow the progression of Parkinson’s disease, revealed University of Warwick researchers. The findings of the study are published in journal Neuro. In the affected dopaminergic neurons, there is accumulation of a specific protein called as alpha synuclein which forms structures called as Lewy bodies. The number of Lewy bodies correlates with the severity of the disease. In the early stage of protein aggregation, these small species have a range of toxic effects is seen, many of which are not fully defined.

Emily Hill from School of Life Sciences at the University of Warwick said,“By only injecting low concentrations of structurally-defined alpha synuclein aggregates into single dopaminergic neurons we can characterise early changes in neuronal function, which may occur before the clinical onset of the disease. We observed that the excitability of the neurons was markedly decreased through the opening of a membrane channel. We then thought if we could block this channel maybe we could prevent these early toxic effects.”

In Parkinson’s disease, for neuroprotective action the ATP-sensitive potassium (KATP) channels are suggested as a potential target for drugs. Glibenclamide is a second generation sulfonylurea which is used in the treatment of diabetes.

In Parkinson’s disease, glibenclamide has an inhibitory action on the ATP-sensitive potassium channels.

Following this inhibitory action, the medication was also able to block neutrophil migration and chemotaxis (movement in response to chemical stimuli).

Pretreatment with B vitamins and Glibenclamide at doses of 1 and 5mg/kg can significantly improve the behavioral symptoms of Parkinson’s disease.

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Dr Mark Wall, from the School of Life Sciences at the University of Warwick added, “ There was some evidence that the membrane channel opened was a type of channel called a KATP channel, which could be blocked by some existing anti-diabetic drugs. We were happily surprised to find that effects of the alpha synuclein aggregates could be greatly reduced by the anti-diabetic drug glibenclamide.”

Emily Hill said,“It is possible that existing drugs could be repurposed for treating different diseases. It is known that patients treated for type two diabetes have less prevalence of Parkinson’s disease. Understanding the mechanisms underlying alpha synuclein pathology in single brain neurons could lead to new therapeutic targets for Parkinson's disease.”

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Source-Medindia