On the ninth floor of Indiana University's towering new medical research and education building in the heart of downtown Indianapolis' $4.3 billion medical campus, IU School of Medicine researchers are looking beyond the brain to treat Parkinson's disease, a neurodegenerative disorder that affects over 1.1 million Americans.
By 2050, up to 25 million people worldwide are expected to have the condition, which affects a person's ability to control their movements and leads to dementia in up to 80% of cases. It carries an estimated annual economic burden of $82.2 billion in the U.S. alone, including healthcare expenses, lost productivity and caregiving costs.
These numbers - as well as the personal experience of a family member with the condition - motivate the work of Malú Gámez Tansey, the James A. Caplin, M.D., Professor of Alzheimer's Research and professor of neurology at the IU School of Medicine. As one of IU's many top experts in the fight against dementia, Tansey's path-breaking work on Parkinson's disease has been supported for the past several decades by major groups including the Michael J. Fox Foundation and the Parkinson's Foundation.
Research that takes risks
"We get funded because we deliver," said Tansey, who leads a multi-institutional team that recently joined an international network of Parkinson's research groups through a $9 million award from Aligning Science Across Parkinson's, in partnership with the Michael J. Fox Foundation. "When you invest in us, you get a discovery; you get published results. Our supporters know we know how to start - and finish - a project."
The lab is also not afraid to take risks, learn from failure and question long-held assumptions in the field, she added.
"We have people who are fearless," Tansey said.
Her team's latest project exemplifies this approach as it investigates the role of immune cell exhaustion on the development of Parkinson's, which has not been widely studied.
The idea is that Parkinson's disease does not strike like a bolt from the blue but rather has real and measurable warning signs that proceed onset, such as an immune system worn out over time by conditions like chronic inflammation, metabolic syndrome, inflammatory bowel disease, or even psoriasis or rheumatoid arthritis.
"We need to think outside the box by looking outside the brain, to shift the paradigm toward the idea that brain disease doesn't always start in the brain," she said. "The more we learn, the more we see that Parkinson's is a multisystem disease that has early manifestations outside the brain in some people."
This might include the gut, the circulatory system, or nerves that spread throughout the body.
"The body is a neighborhood, and neighborhood matters," Tansey said. "Neurons don't survive alone, and they do not die alone. They have a whole support system of other cells inside the body, and they can get worn out. They need rehab or rebooting.
"We're looking for ways to make that system work better - to test whether we can delay or slow down age-related neurodegenerative diseases like Parkinson's, but also like Alzheimer's or other related disorders."
A brain health powerhouse
The work does not take place in isolation. The Stark Neurosciences Research Institute at the IU School of Medicine - the country's largest school of medicine - has attracted tremendous investment over the past decade, with nearly $680 million in grant funding since 2016. It also boasts more than 130 investigators studying neurological disease and related topics such as psychiatric disorders, traumatic brain injury and chronic pain. IU has continued to invest an ambitious $250 million to strengthen the university's leadership in biosciences since 2023 alone.
The concentration of these resources fosters new talent in the fight against Parkinson's disease. Research on immune cell exhaustion by IU School of Medicine assistant professor Rebecca Wallings provided the foundation of the Tansey lab's new grant-funded project; Wallings serves as one of the project's co-leaders.
"Over the last 20 years, the field has regarded inflammation as a condition that is heightened in Parkinson's disease and needs suppression," said Wallings, a former postdoctoral researcher in Tansey's lab. "But our data suggests that the immune system of an individual with Parkinson's disease may in fact be exhausted, meaning immunosuppressive therapies could be deleterious. We need to think about new therapeutic approaches that reinvigorate the immune system."
"IU is already a powerhouse in the area of brain health," Tansey said. "We've got world-renowned researchers in Alzheimer's and movement disorders. This is a place with people who can get the science done."
Identifying warning signs
IU is home to leading research resources such as the Michael J. Fox Foundation Biorepository, which houses physical samples from thousands of Parkinson's patients along with control samples, as well as medical records and imaging data. Altogether the resource comprises the most robust library of Parkinson's-related data in the world, helping researchers understand what may trigger the condition.
Individuals with inflammatory bowel or Crohn's disease have a 45% greater risk of Parkinson's later in life, for example. Certain sleep disorders that are common in people with Parkinson's may also offer clues.
Understanding the connection between these disorders and neurodegenerative diseases could lead to easily identifiable warning signs, Tansey said.
"We no longer wait for you to have a heart attack," she said. "Your doctor knows what proteins to monitor in your blood so they can intervene early."
The same could be true of neurodegenerative disease in the future.
"We're not out to increase lifespan but health span - to give people the opportunity to live longer independently; to enjoy their spouse, or partner, or children or grandchildren, and live without the fear of becoming dependent due to a debilitating neurodegenerative condition," Tansey said. "We envision a world where these conditions are treated as completely preventable because we know how to identify people at risk at middle age and then take the right steps to protect them early on."
