GARY E. LANDRETH, Ph.D.
Case Western Reserve University

“Efficacy of PPARg Agonists in Treatment of Glioma”

Dr. Landreth‘s project is focused on the development of new therapy to slow or stop tumor growth and its invasion of the surrounding brain tissue.  Dr. Landreth will use a drug (approved for the treatment of type II diabetes) to target the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ), which works by physically associating with DNA and changing gene expression.  There is preliminary data demonstrating the efficacy of PPARγ agonists in suppressing the growth and migration of human glioma cells in vitro as well as in animal glioma models.

The primary goal of the study is to establish how best to administer the drug – either orally or through a device implanted directly into the tumor – and identify the appropriate dosage of drug necessary to block tumor growth.  A second aim is to establish if there are pharmacogenetic considerations in use of this therapy related to the tumor suppressor PTEN, which is a target of PPARγ.   

PPARγ agonists act principally in fatty tissue to stimulate fatty acid metabolism, sensitize tissues to insulin action and modulate blood glucose levels.  As a consequence, agonists of PPARγ have been developed for treatment of type II diabetes.  Two members of the thiazolidinedione (TZD) class of PPARγ agonists are FDA approved (pioglitazone, ActosTM; rosiglitazone; AvandiaTM) and are widely prescribed for this indication. 

Data on drug dosage and delivery are essential prerequisites for an Investigational New Drug (IND) filing.  As Dr. Landreth and his team are using an FDA approved drug, pioglitazone, it is hoped that a successful investigation could facilitate the rapid translation of these clinical studies into treatment for patients.

 

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