April 11th is World Parkinson's Day. We are featuring Jeffery Kordower who is leading research in neurodegenerative diseases here at the Biodesign Institute.
The two most common neurodegenerative disorders in the U.S. turn life into a downward spiral for the estimated 6.7 million Americans with Alzheimer’s disease and as many as 1 million with Parkinson’s.
Alzheimer’s slowly destroys memory and thinking skills, and eventually, the ability to carry out the simplest tasks. Parkinson’s takes a heavier toll on the body, creating tremors and motor difficulties that can worsen to the point where it may be impossible to stand or walk without assistance.
At the ASU-Banner Neurodegenerative Disease Research Center, researchers are unlocking mysteries about the diseases in the hopes of finding effective treatments — if not a cure. The center is part of the Biodesign Institute at Arizona State University.
Researchers are exploring strategies for replacing depleted neurons to reverse the debilitating symptoms of Parkinson’s disease. Kordower is on the forefront of promising new research into so-called neural grafting, in which stem cells are directly implanted in the brain.
In other research in collaboration with ASU’s School of Molecular Sciences and the Banner Brain and Body Donation Center, Ramon Velazquez had presets evidence that low levels of choline in the bloodstream are associated with increased severity of Alzheimer’s disease pathology in the brain. Approximately 90% of Americans are deficient in choline, an essential nutrient that’s vital for neurological health as well as liver and metabolic function.
The center’s innovative approach to health solutions draws from the overarching mission of the Biodesign Institute, which is celebrating its 20th anniversary throughout 2024.
Below, Kordower shares his insights into the center’s research. Answers are edited for length and clarity.
Question: What is the research focus of your center?
Answer: The center is on a quest to reduce the symptoms of neurodegenerative diseases such as Alzheimer’s and Parkinson’s and ultimately find a cure. Caring for someone with a neurodegenerative disease can feel like a tremendous burden, and our other mission is to find ways to help caregivers. We have outstanding undergraduate and graduate students as well as postdoctoral fellows working here, and our job is to train them to become the next generation of impactful neuroscientists.
Q: Why is this work important to society?
A: There will be 25 million to 30 million people with Alzheimer’s and 15 million people with Parkinson’s worldwide by 2040. While the cost in human suffering is incalculable, the financial cost to sustain this pandemic of neurodegenerative diseases will be astronomical. We need to make a major impact soon to help people and society overall.
Q: What is the biggest challenge in this field of research?
A: There are many challenges because these diseases are complicated. Many clinical trials never recruit a single patient. With the website clinicaltrials.gov, there’s an easy avenue to enroll in a study, but these people are sick, and coming to a doctor’s office multiple times can be a burden. As researchers, we need more patients to participate in clinical trials so we can test drugs and other therapies moving forward. Also, there’s always the issue of money — being able to get enough grant money to conduct research.
Q: What is something you consider one of the center’s biggest successes?
A: Several things are percolating up, but it’s a little too early to claim victory. I just became the principal investigator of a clinical trial funded by the Michael J. Fox Foundation to do stem cell transplants in patients with a genetic form of Parkinson’s disease. We will infuse specially designed stem cells into a region of their brains called the putamen, where dopamine is lost due to the disease. We expect patients receiving the new cells to show improvements in symptoms in six to 12 months. If we achieve successful results in this clinical trial of patients with a genetic mutation, it will encourage further trials in a wider population of Parkinson’s patients.
My colleagues are doing super work in preclinical trials. For example, Ramon Velazquez has discovered that low levels of choline in the bloodstream are associated with increased severity of Alzheimer’s disease pathology in the brain. The research offers hope that supplying sufficient choline may help to protect the brain from Alzheimer’s disease or at least delay its onset.
Q: How are students involved in the center’s research?
A: When I first came here a couple of years ago, I gave a lecture in an undergraduate course and told the students that anyone who wants to do research should stop by my office. The next day, I had nine students outside my door, and I took them all. I very rarely turn anyone away. I have three graduate and six undergraduate students in my lab right now. One of the reasons why I became successful is my mentor demonstrated to me how exciting science could be, and I try to provide that environment to students.
Q: If someone gave your center $100 million, what would you do with it?
A: I would expand the focus of the center to include other types of dementia, such as Lewy body dementia. Cognitive decline is a huge problem with other diseases like frontotemporal dementia, sometimes called Pick’s disease, and multiple system atrophy, so I’d expand the breadth of our faculty researchers. I’d love to put an imaging center here so we could do our own PET and MRI scanning. Right now, I do all these scans at Barrow Neurological Institute.
Q: How did you become interested in science, and in particular, the field you are in?
A: I wasn’t doing well in college, and I knew I needed to get some extra credit. A developmental psychology professor was looking for volunteers to do research, and I volunteered, even though I wasn’t really interested in the research she was doing. But a new assistant professor named Richard Bodnar who was studying pain perception and analgesia moved in across the hall. That was something that interested me, and so I started working in his lab and fell in love with science. We were incredibly successful together, and I published 10 papers as an undergraduate and graduate student.
Afterward, I attended a Society for Neuroscience meeting, where I met Don Gash, who presented his research during a seminar on brain cell transplantation. He was transplanting cells that made a peptide called vasopressin. My doctoral thesis was on vasopressin pain and analgesia processes, so it seemed like a good match. I applied for a postdoctoral fellowship with his research team at the University of Rochester Medical Center and was accepted. When I arrived, he’d changed the entire direction of his research to Parkinson’s disease, which turned out to be fantastic for me.
Q: What is the most fun aspect of your work in the center?
A: It’s the discovery. My colleagues and I recently discovered the role of a critical protein called tau in the neural degeneration of patients with Parkinson’s disease. Our findings challenge the conventional view of Parkinson’s disease pathology, which typically focuses on the protein alpha-synuclein as the classic diagnostic hallmark of the disease. Our study was published in the well-respected journal Brain, and it’s so exciting that our discovery could shift the focus of Parkinson’s disease research, diagnosis and treatment.
Q: Describe your experience with Biodesign’s collaborative, interdisciplinary research culture.
A: Biodesign researchers are smart, committed and good collaborators. We accelerate each other’s research. In the past, researchers worked alone in their own lab, but it’s impossible to make a major impact that way anymore. You need collaborators; it takes a team.