“The PDF Côté Award [in Clinical Genetics] helped me to start my research.”
Sheng-Han Kuo, M.D.
Discovering what causes Parkinson’s disease (PD), and finding its cure, will require marshaling to these tasks the best scientific minds. That’s why preparing the scientific leaders of the future is central to the mission of the Parkinson’s Disease Foundation (PDF). To date, PDF has funded fellowships for more than 100 young neurologists as they undertake the additional years of training that they need to become specialists who can both care for people with PD and conduct scientific research. Sheng-Han Kuo, M.D., at the PDF Research Center at Columbia University Medical Center, is one of these talented individuals.
Dr. Kuo arrived at Columbia University in 2009, after completing his residency in neurology at Baylor College of Medicine in Houston. Then, with two years of financial support from PDF, he took his clinical training to the next level, becoming qualified as a movement disorder specialist — the type of doctor who has the greatest level of expertise in treating PD.
Today Dr. Kuo not only cares for people with PD; he also spends much of this time in the lab studying the genetics of the disease. Again, it was PDF that provided support to advance Dr. Kuo’s career. In 2012, he was one of the first recipients of PDF’s Lucien Côté Early Investigator Award in Clinical Genetics. Genes play an important role in the development of PD, and this award advances research to identify genetic markers of PD and to understand how genetic changes contribute to disease. It also gives young scientists the opportunity to do the research necessary to develop careers as independent investigators.
“I am interested in the common mechanisms that underlie all of PD,” says Dr. Kuo. Over time, all people with PD lose dopamine neurons, which help control movement. And the damaged neurons accumulate toxic clumps of a protein called alpha-synuclein.
“The focus of my work is to study changes in a gene known as GBA (glucocerebrosidase), which is known to affect the clumping of alpha-synuclein, and — in a mutated form — serves as the most common genetic risk factor for PD,” he says. About seven percent of people with PD carry GBA mutations.
With his PDF award, Dr. Kuo collaborated with scientists at the New York Stem Cell Foundation to create dopamine neurons with a Parkinson’s GBA mutation that can be studied in the laboratory. Using techniques involving adult stem cells, he started with skin cells taken from a person with PD who had the GBA gene, and transformed them into dopamine neurons. Dr. Kuo notes that although studying Parkinson’s disease in animal models is valuable, it is critical to study the disease in human cells. According to Dr. Kuo, this is because, “Parkinson’s disease is a humanspecific disorder.”
These cells, when compared to similar cells derived from a person who does not have a GBA mutation, displayed many properties associated with PD — that is, as more alpha-synuclein accumulated, less dopamine was released, GBA was less active, and the structure of the cells was abnormal.
Having created these dopamine neurons, Dr. Kuo can now use them to investigate how changes in GBA disrupt a cell’s ability to dispose of alpha-synuclein. Ultimately, such cells also might be used to screen potential PD therapies for their ability to correct what goes wrong in cells that have GBA mutations.
Besides helping him pursue his research, Dr. Kuo’s PDF-supported project also helped prepare him to become a principal investigator, expertise that will be essential to his ability to secure future funding to continue his studies. He has already received grants from several sources, including the National Institutes of Health. Says Dr. Kuo, “The PDF Côté Award helped me to start my research.”