Innovative strategy can reverse symptoms in neurodegenerative diseases

Alzheimer's and Parkinson's disease are the two most common neurodegenerative disorders worldwide and cause untold suffering to millions of patients and their families. Treatments for these diseases are limited, and no cures exist. Now, a new study describes an innovative strategy that reverses symptoms in these neurodegenerative diseases - at least in fruit flies which had been genetically altered to model the diseases.

"The novel approach we used has significant translational implications," said one of the lead authors, Robert Schwarcz, a researcher in the Department of Psychiatry at the University of Maryland School of Medicine. "If we can duplicate these effects in patients, we could benefit a lot of people."

Schwarcz collaborated with geneticist Flaviano Giorgini at the University of Leicester in England. The study was published today in the journal Proceedings of the National Academy of Sciences.

The researchers focused on metabolites related to the amino acid tryptophan. When tryptophan degrades in the body, it breaks down into several compounds that have biological activities in the nervous system. One of these, 3-hydroxykynurenine (3-HK), has neurotoxic properties whereas another, named kynurenic acid (KYNA), has the ability to prevent nerve cell degeneration. The relative abundance of these two compounds in the brain may be critical in Alzheimer's and Parkinson's disease, and also Huntington's disease.

Schwarcz, Giorgini and their colleagues gave the insects a chemical that selectively inhibits tryptophan-2,3-dioxygenase (TDO), an enzyme that controls the relationship between 3-HK and KYNA. This treatment shifted metabolism towards more KYNA, improved movement, and lengthened lifespan in the fly models of the diseases.

"A key finding of our study is that we can improve "symptoms" in fruit fly models of Alzheimer's and Parkinson's disease by feeding them a drug-like chemical," said another co-author, Carlo Breda of the University of Leicester. "Our experiments have identified TDO as a very promising new drug target."

The next steps will involve testing of the new concept in humans and to examine whether the treatment works for neurodegenerative diseases.