UM SOM Identifies Compound That Reverses Symptoms of Alzheimer's and Parkinson's Diseases

Research in Flies Could Have Major Implications for Human Disease

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 genetically altered to model the diseases.

“The novel approach we used has significant translational implications,” said one of the lead authors, Robert Schwarcz, PhD, a Professor in the Department of Psychiatry at the University of Maryland School of Medicine (UM SOM). “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 last month 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.

“Dr. Schwarcz’s work illustrates how our school is collaborating with others around the globe to discover ways of treating the most debilitating diseases,” said UM SOM Dean E. Albert Reece, MD, PhD, MBA, who is also the vice president for Medical Affairs, University of Maryland, and the John Z. and Akiko K. Bowers Distinguished Professor. “These results hold out the promise of important future clinical breakthroughs, which could potentially change the lives of millions of patients.”

About the University of Maryland School of Medicine

The University of Maryland School of Medicine was chartered in 1807 and is the first public medical school in the United States and continues today as an innovative leader in accelerating innovation and discovery in medicine. The School of Medicine is the founding school of the University of Maryland and is an integral part of the 11-campus University System of Maryland. Located on the University of Maryland’s Baltimore campus, the School of Medicine works closely with the University of Maryland Medical Center and Medical System to provide a research-intensive, academic and clinically based education. With 43 academic departments, centers and institutes and a faculty of more than 3,000 physicians and research scientists plus more than $400 million in extramural funding, the School is regarded as one of the leading biomedical research institutions in the U.S. with top-tier faculty and programs in cancer, brain science, surgery and transplantation, trauma and emergency medicine, vaccine development and human genomics, among other centers of excellence. The School is not only concerned with the health of the citizens of Maryland and the nation, but also has a global presence, with research and treatment facilities in more than 35 countries around the world. http://medschool.umaryland.edu/