A roundup of recent research out of the School of Medicine

New hope for breathing recovery after spinal cord injuries

Story By: Patty Zamora

About 300,000 Americans live with spinal cord injuries, and related respiratory complications are the leading cause of illness and death, according to the Christopher & Dana Reeve Foundation. 
But a new study led by Case Western Reserve University School of Medicine researchers offers hope for patients who struggle to breathe on their own. Their findings were recently published in the journal Cell Reports.

Led by Polyxeni Philippidou, PhD, an associate professor in the Department of Neurosciences, the researchers identified a group of nerve cells in the spinal cord—interneurons—that can boost breathing when the body faces certain physiological challenges, such as exercise and environmental conditions associated with altitude. 

“While we know the brainstem sets the rhythm for breathing,” said Philippidou, also the Weidenthal Family Designated Professor in Career Development, “the exact pathways that increase respiratory motor neuron output, have been unclear—until now.”

The research team included collaborators from the University of St. Andrews in the United Kingdom, the University of Calgary in Canada and the Biomedical Research Foundation Academy of Athens in Greece. 

Uncovering an HIV mystery that could unlock the key to a cure

Story By: Patty Zamora

For more than 30 years, HIV has eluded scientists by hiding within infected cells. That makes treating—and possibly even curing—the disease seemingly insurmountable. But researchers at Case Western Reserve University School of Medicine have made a major breakthrough that could fundamentally change strategies for HIV treatment.

In a study published in the journal Nature Microbiology, the researchers identified for the first time how HIV enters a dormant state, allowing it to “hide” from both the immune system and existing therapies. 

“This discovery rewrites what we thought we knew about how HIV goes into this stealth mode in the human body,” said lead researcher Saba Valadkhan, MD, PhD, an associate professor in the Department of Molecular Biology and Microbiology at the medical school.

“This discovery rewrites what we thought we knew about how HIV goes into this stealth mode in the human body.”

—Saba Valdkhan, MD, PhD, associate professor, Department of Molecular Biology and Microbiology at CWRU School of Medicine

The virus inserts its genetic material into a cell’s DNA, then triggers the cell—and itself—to go dormant, making them both invisible and unreachable by even the most advanced HIV drugs. The virus then stays hidden until the right moment to “wake up” and spread again. “What we’ve uncovered is that HIV doesn’t just randomly go dormant—it actively manipulates the host cell to create conditions for its own survival,” said study collaborator Jonathan Karn, PhD, a Distinguished University Professor and chair of the molecular biology and microbiology department.

The researchers are now developing treatments. They also believe similar dormancy actions could be triggered by other viruses—including herpes, hepatitis and other retroviruses—potentially leading to new therapies for many viral diseases. 

Expanding the donor pool

Study finds that corneas from donors with diabetes are just as effective for transplant surgery

Story By: Patty Zamora

Many eye banks won’t accept corneas from donors with diabetes, concerned they might be harder to prepare for transplant surgery or are more likely to fail.

But a new study led by researchers at CWRU School of Medicine and University Hospitals found no significant difference in those who received corneas from donors with diabetes compared to donors without the disease one year after surgery. The study involved 1,097 patients who had Descemet membrane endothelial keratoplasty (DMEK) transplant surgery, which replaces the innermost, diseased layer of the cornea with a single layer of healthy cells. 

“We also found the severity of the donor’s diabetes did not affect transplant outcomes and the corneal structure remained healthy across all groups,” said Jonathan Lass, MD, the Charles I Thomas Professor in the Department of Ophthalmology and Visual Sciences at the medical school and the lead researcher of the study published in the journal JAMA Ophthalmology.

The findings are “good news for eye banks because they demonstrate that people with diabetes can be cornea donors, increasing the number of people whose sight can be restored, and lives transformed, through transplant procedures,” said Kevin Corcoran, president and CEO of the Eye Bank Association of America. 

Study links help within days for serious head injuries to lower risk for alzheimer's

Story By: Patty Zamora

New research from CWRU School of Medicine found that treatment within one week of a serious head injury can reduce the risk of developing Alzheimer’s disease.

The medical school researchers analyzed health records from more than 100 million patients in the United States and identified 37,000 people ages 50 to 90 who suffered moderate or severe brain injuries. 

Their study—published in the Journal of Alzheimer’s Disease—found that people who received treatment within one week had a 41% lower risk of developing Alzheimer’s at three years and a 30% lower risk at five years compared to those who received delayed treatment.

“Our analysis shows that acting quickly matters in the long term,” said Austin Kennemer, a third-year medical student who co-led the research with Zhenxiang Gao, PhD, a research assistant professor. Rong Xu, PhD (GRS ’99, biology), a professor of biomedical informatics and director of the medical school’s Center for Artificial Intelligence in Drug Discovery, supervised the work. 

Popular diabetes and weight-loss drugs may reduce risk of dementia

Story By: Patty Zamora

CWRU School of Medicine researchers have found that semaglutide—the active ingredient in popular diabetes and weight-loss drugs—may lower the risk of dementia in people with type 2 diabetes (T2D).

Their study, recently published in the Journal of Alzheimer’s Disease, analyzed three years of electronic health records of nearly 1.7 million T2D patients nationally. It suggests patients with T2D who are taking drugs that include semaglutide had a significantly lower risk of developing dementia compared to those taking other antidiabetic medications. The results were greater in women and older adults.

Semaglutide is the active component in diabetes and weight-loss drugs such as Wegovy and Ozempic and has shown a broad range of benefits.

“There is no cure or effective treatment for dementia,” said Rong Xu, PhD (GRS ’99, biology), the study’s lead author, a professor of biomedical informatics and director of the medical school’s Center for Artificial Intelligence in Drug Discovery. “So, this new study provides real-world evidence for its potential impact on preventing or slowing dementia development” among populations at high risk.

But Xu said the study had limitations and that the use of semaglutide for dementia prevention will need to be further investigated through randomized clinical trials.

“This new study provides real-world evidence for its potential impact on preventing or slowing dementia development”

—Rong Xu, PhD, director and professor, Center for Artificial Intelligence in Drug Discovery at CWRU School of Medicine