INDIANAPOLIS - Indiana University School of Medicine researchers have identified a portfolio of novel drug targets that may accelerate promising treatments for patients living with Alzheimer's disease.
For more than half a decade, the IU-led TREAT-AD drug discovery center - Target Enablement to Accelerate Therapy Development for Alzheimer's Disease - has spearheaded this integral research to reinvigorate and grow the pipeline of potential therapeutics for Alzheimer's disease. The center is a partnership between researchers at the IU School of Medicine, Purdue University, the Indiana Biosciences Research Institute, Lgenia Inc. and the University of Pittsburgh.
Avi Benitah, a postdoctoral fellow at the IU School of Medicine, works in an Indiana Biosciences Research Institute lab. The institute is a key partner in the IU-led TREAT-AD center, which aims to discover and study new therapeutic targets to treat Alzheimer's disease. Photo by Liz Kaye, Indiana University" src="https://news.iu.edu/live/image/gid/2/width/500/height/334/20787_20250117_Chemistry_Lab_16Tech_LK_010_1.rev.1737576735.jpg" title="20250117 IBRI Lab & Portraits (LK)" srcset="https://news.iu.edu/live/image/scale/2x/gid/2/width/500/height/334/20787_20250117_Chemistry_Lab_16Tech_LK_010_1.rev.1737576735.jpg 2x, /live/image/scale/3x/gid/2/width/500/height/334/20787_20250117_Chemistry_Lab_16Tech_LK_010_1.rev.1737576735.jpg 3x" data-max-w="2400" data-max-h="1601" loading="lazy" data-optimized="true"/>
Avi Benitah, a postdoctoral fellow at the IU School of Medicine, works in an Indiana Biosciences Research Institute lab. The institute is a key partner in the IU-led TREAT-AD center, which aims to discover and study new therapeutic targets to treat Alzheimer's disease. Photo by Liz Kaye, Indiana University
"What has been collectively accomplished across the IU School of Medicine over the past several years has begun to solidify a true center of excellence that investigates the basic science of Alzheimer's disease, translates it to therapeutic opportunities and develops a pathway for next-generation clinical studies," said Alan Palkowitz, senior research professor of medicine at the IU School of Medicine.
Palkowitz leads the drug discovery center with co-principal investigators IU Distinguished Professor Bruce T. Lamb, executive director of the Stark Neurosciences Research Institute and the Roberts Family Professor of Alzheimer's Disease Research at the IU School of Medicine; and Timothy Richardson, senior research professor of medicine at the IU School of Medicine.
"What is truly unique about the TREAT-AD Center is the expertise of the faculty, staff and trainees who work in both academia and the pharmaceutical industry - from bioinformatics and structural biology to medicinal chemistry and clinical research," Lamb said. "We're among only a few centers in the United States that bring together this talented of a group focused on Alzheimer's disease drug discovery."
According to the Alzheimer's Association, more than 7 million Americans are living with Alzheimer's disease. By 2050, this number is projected to increase to nearly 13 million.
In December 2024, the National Institute on Aging, the largest branch for Alzheimer's disease research within the National Institutes of Health, awarded TREAT-AD a five-year, $41.6 million grant renewal. Established in 2019, TREAT-AD initially focused on hundreds of proteins, or targets, related to the function of microglia - the brain's immune cells - that may contribute to and protect against Alzheimer's disease. The team narrowed down a list of hundreds of potential targets to 30 and then focused on building a portfolio of five that are particularly promising as potential new therapies.
IU School of Medicine's Tim Richardson, left, and Alan Palkowitz are co-leaders of TREAT-AD, along with Bruce Lamb (not pictured). Photo by Liz Kaye, Indiana University" src="https://news.iu.edu/live/image/gid/2/width/609/height/406/20788_20250117_Alan_Palkowitz_and_Tim_Richardson_LK_427.rev.1737576956.jpg" title="20250117 IBRI Lab & Portraits (LK)" srcset="https://news.iu.edu/live/image/scale/2x/gid/2/width/609/height/406/20788_20250117_Alan_Palkowitz_and_Tim_Richardson_LK_427.rev.1737576956.jpg 2x, /live/image/scale/3x/gid/2/width/609/height/406/20788_20250117_Alan_Palkowitz_and_Tim_Richardson_LK_427.rev.1737576956.jpg 3x" data-max-w="2400" data-max-h="1601" loading="lazy" data-optimized="true"/>
IU School of Medicine's Tim Richardson, left, and Alan Palkowitz are co-leaders of TREAT-AD, along with Bruce Lamb (not pictured). Photo by Liz Kaye, Indiana University
The most advanced target is SHIP1, encoded by INPP5D, a microglia-specific gene that has been associated with late-onset Alzheimer's disease. Building on the foundational work of TREAT-AD to enable the development of a program targeting SHIP1, the IU School of Medicine also received a five-year, $11.3 million grant to advance a SHIP1 inhibitor into clinical trials.
"The success of TREAT-AD continues to bolster the IU School of Medicine's reputation as one of the nation's preeminent Alzheimer's disease research programs," said Dr. Jay L. Hess, dean of the IU School of Medicine and executive vice president for university clinical affairs at IU. "We are honored that the NIH has renewed funding for this critical program. This funding will help speed the development of promising new drug candidates for this deadly disease."
The contributing regional institutions and companies bring together diverse scientific expertise and capabilities to the TREAT-AD center and are a key factor in its enduring success.
Palkowitz, who is also president and CEO of the Indiana Biosciences Research Institute, said the nonprofit research institute's strong background in drug discovery and translational research complements the leading Alzheimer's research at the IU School of Medicine and the structural biology and biophysics expertise at Purdue. Last year, IU and the institute, which houses a portion of the TREAT-AD laboratories at the 16 Tech Innovation District in downtown Indianapolis, formed a center to advance point-of-care precision medicine.
Over the next five years, Palkowitz said, TREAT-AD will look beyond the brain's immune system and broaden its scope into investigating additional drivers of neuroinflammation in the brain and how it connects to later stages of Alzheimer's disease. Investigators will also expand their toolbox of drug targets and study antibodies and oligonucleotides, known as silencing RNAs.
The center also plans to place a larger emphasis on biomarkers - indicators in the body that Alzheimer's pathology is present - through the work of Jeff Dage, senior research professor of neurology at the IU School of Medicine. Dage led the discovery and development of phosphorylated tau 217 as a novel blood biomarker for Alzheimer's disease clinical trials, which helped lead to recent FDA clearance of the first blood test for Alzheimer's.
"We envision biomarkers as an important part to enable the study of new targets and potential new drug molecules, not only for understanding an individual patient's disease, but for monitoring the effectiveness of these novel treatments," Palkowitz said.
