Novel ''prodrug'' may help fight Huntington''s, Alzheimer''s

Novel ''prodrug'' may help fight Huntington''s, Alzheimer''sWashington, June 3: Researchers have developed a new `prodrug' slow-release compound that can protect mice from the neurodegenerative effects of both Huntington''s and Alzheimer''s disease.

The ''prodrug'' known as JM6 works through a pathway involved in the breakdown of the amino acid tryptophan.

"Most would have assumed that the drug would have to enter the brain to have an effect," said Paul Muchowski of the University of California, San Francisco.

The study promises to pave the way to new strategies for the treatment of brain diseases more broadly.

The researchers first treated mice having Huntington''s disease with JM6. Chronic delivery of JM6 inhibited enzyme called kynurenine 3-monooxygenase or KMO in the animals'' blood.

This increased kynurenic acid levels and reduced extra cellular levels of the chemical messenger glutamate in the brain.

According to Muchowski, those mice, which normally would have died by the time they were 15 weeks old, lived about 40 pc longer. Their motor coordination improved and they were protected against the loss of the synapses that serve as critical junctions in the neural circuitry.

It was observed that in a transgenic mouse model of Alzheimer''s disease, JM6 prevented spatial memory deficits, anxiety-related behaviour and the loss of synapses. "JM6 helped the animals remember," Muchowski added.

Alzheimer''s mice also become uninhibited and will run right out of the safety of the dark and into open spaces, a risky habit in the real world where predators lurk. "JM6 completely rescued that deficit."

The study findings appear in the online publication of Cell. (ANI)