Jay Iyer

Mass General researcher and Harvard College senior Jay Iyer was born and raised in Baton Rouge, Louisiana, where he lived with his parents and grandparents.

His grandfather, Mani Iyer or "Thatha" was born in Mumbai, India and graduated from Veermata Jijabai Technological Institute (VJTI) with a Master’s degree in textile engineering.

Led by Mani, the Iyer family immigrated to the United States in the early 1980s, where Mani served as the Director of the Office of Innovation and Technology at Louisiana State University (LSU) for almost 20 years.

Mani Iyer "Thatha"

Mani retired in 2006 as Director Emeritus to enjoy time with his family and his many hobbies, especially tending to his garden filled with flowers, vegetables and Indian spice plants.

Jay fondly traces his love of scientific inquiry back to the age of four and time spent with his grandfather in their backyard garden. “He was the actually the one to instill the scientific method in me by doing experiments in the garden where we would grow Indian spices,” Jay reminisces.

Those days were filled with the rich scents of the spices his grandfather carefully nurtured—a cherished tradition in their traditional Indian household, forming a bond that wove their lives together.

Their time in the garden, once a source of joy and connection, then became a distant memory.

Mani's symptoms first started in 2014 with restless legs syndrome–a compulsion to move his legs at night. In February of 2015, he started to have difficulty concentrating.

In March of 2015, Mani had difficulty walking in a straight line and developed apraxia (a neurological disorder that impacts speech).

Jay with his grandfather, Mani, at the age of six

Later, Mani fell out of bed and fractured his nose and one of his toes, prompting the family to see a neuropsychologist for an evaluation. He was initially diagnosed with Parkinson's disease.

Throughout the rest of 2015, Mani developed micrographia (abnormally small, cramped handwriting) and had issues with his eye convergence (using both eyes to focus in on close-up objects).

After numerous visits with neurologists, the family finally received the devastating diagnosis of progressive supranuclear palsy (PSP) in 2016.

PSP is a rare disease affecting five to six out of every 100,000 people. The disease, which has no known cause or cure, affects the brain cells that control balance, walking, coordination, eye movement, speech, swallowing and thinking.

Symptoms can include a loss of balance, changes in personality and weakened movements of the eyes, mouth, tongue and throat, among others.

Jay became one of his grandfather’s primary caretakers during his three-year-long battle with the disease, spending his time outside of school by his Mani's bedside.

"I would do whatever I could to improve his quality of life and provide him company, from installing grab-bars around the house to bed railings to help him from falling out of bed," Jay recalls. "Sometimes this meant watching his favorite Hindi movies together or talking about current world events.”

The diagnosis was challenging for Iyer and his Louisiana-based family, as they struggled to find resources in the area to help with his grandfather’s care with PSP compared with better-known illnesses. This led them to start a nonprofit called MIND Relief to help PSP patients and their families with questions about the disease.

Jay listens to Mani’s heart, aided by his aunt, an OBGYN

Throughout 2018, Mani was on hospice care for twenty-four hours a day, and Jay can recall many incidents where his grandfather fell before losing all ability to walk. In February of 2019, Mani passed away.

As Jay witnessed the debilitating effects of PSP as he cared for his grandfather, he grew frustrated by the lack of available treatments.

“If you think of having issues with the kidney, liver or heart, there are a lot of things you can do to potentially start to treat it,” he says. “But the brain is so complex and it’s so difficult to develop treatments for these types of diseases. I really wanted to start figuring out a way to work for a cure.”

Iyer has already made a lot of progress fulfilling that promise to his grandfather and to other families affected by these conditions.

As a 15-year-old high school student, he worked on designing drugs for the degradation of Tau, a protein that is involved in the pathogenesis of PSP. He then worked with a team of scientists from UCLA, including X. William Yang, MD, PhD, and Peter Langfelder, PhD, identifying more than 2,000 proteins associated with Huntington’s disease pathogenesis.

Anne-Marie Wills, MD, MPH

When Jay arrived at Harvard as an undergraduate student a few years ago, he approached Anne-Marie Wills, MD, MPH, to see if he could help with the clinic’s research efforts. Wills is director of the Mass General Progressive Supranuclear Palsy Clinic, which has been designated a CurePSP Center of Care by the CurePSP Foundation, the leading foundation for PSP research and care.

“One of the things we work on is mining completed clinical trials to try to come up with ideas for disease modification,” says Wills. “Jay’s been fantastic—he applies his interest, his incredible energy level, and his skills in terms of computer analysis and data analysis to this really under-researched, under-investigated disease.”

“One thing that has definitely surprised me is the amount we can gain from well-described clinical data,” adds Jay. “Just by looking at a few data sets and the medications people are taking, I learned we can find something that is novel and has a lot of clinical and pathological relevance.”

Iyer and family celebrating the Mani's memory in the garden where he loved to spend time.

Iyer is the first author on a recent study in JAMA Neurology in which he, Willis and colleagues conducted a secondary analysis of clinical data collected for a 2010-2012 study testing a potential treatment for PSP.

While the treatment being tested in the trial did not prove effective, there were still insights to be found in the data collected from participants.

The researchers compared all the medications taken concurrently by at least 10% of participants in the treatment and placebo arms of the study.

Their analysis showed that one class of medication—benzodiazepine derivatives such as Ativan, Klonopin and Xanax—were associated with a rapid worsening of the PSP Rating Scale (PSPRS) between weeks 26 and 52 of the study.

“Patients with PSP are commonly prescribed low-dose benzodiazepines, but our findings suggest that participants who received even low-dose benzodiazepines experienced an increased rate of worsening on the PSPRS,” Iyer and colleagues write.

For Jay, who is on a premedical track at Harvard with hopes of becoming a neurologist specializing in Parkinson-plus syndromes, the findings are the first of what he hopes to be many contributions he can make to improve care for PSP patients.

“My personal interest—coupled with the fact that I am really fortunate to have incredible mentors and to be in this place with Harvard and Mass General right nearby—I think it’s just the perfect combination for me to contribute to this disease." — Jay Iyer