IRP Discoveries

An Unlikely Target in the Fight Against Alzheimer’s

IRP Researchers Find Link Between Dementia and Byproducts of Cholesterol Breakdown

old man in nursing home

When most people think about Alzheimer’s disease, the liver is probably the organ least likely to come to mind. Yet recent IRP research suggests that molecules called bile acids, which are synthesized in the liver, may influence the development of Alzheimer’s disease. In honor of Brain Awareness Week this week, we’re diving into that work to learn how such an unlikely target could help lead to new treatments for Alzheimer’s and other forms of dementia.

To date, efforts to develop therapies for Alzheimer’s disease, which affects more than 6 million Americans over the age of 65, have achieved little success. Many scientists are focused on proteins in the brain as potential treatment targets, including the ‘amyloid-beta’ protein now infamous amongst Alzheimer’s researchers. In contrast, IRP senior investigator Madhav Thambisetty, M.D., Ph.D., has been exploring the role that cholesterol might play in the development of Alzheimer’s and vascular dementia, which is marked by microscopic bleeding and blood vessel blockage and is the second most common form of dementia.

Drug Duo Stokes Body’s Fat-Burning Furnace

Mouse Study Suggests Treatment Strategy Could Benefit Patients with Obesity

fire

It’s bad enough that the excess abdominal fat carried by most individuals with obesity causes widespread inflammation throughout their bodies. To add insult to injury, that inflammation actually makes it harder to use up overloaded fat stores. However, a new IRP mouse study supports a two-pronged pharmaceutical approach that could break this vicious cycle and help improve the health of people with obesity.

Mislabeled Proteins Linked to Birth Defects

IRP Researchers Discover Genetic Disorder Affecting the Brain and Skull

baby

A baby is born with a birth defect every four and a half minutes in the United States, adding up to one in every 33 babies born each year in this country. While some birth defects can be corrected or treated, many result in life-altering disabilities, and sometimes the child doesn’t survive. In fact, birth defects account for about 20 percent of infant deaths in the U.S. World Birth Defects Day, celebrated on March 3 each year, honors the people and organizations who are working to understand, prevent, and treat birth defects.

One of these organizations is the Undiagnosed Diseases Program (UDP) at NIH, which connects experts across the IRP’s 23 Institutes and Centers in a joint effort to find explanations for the “most puzzling medical cases" referred to the NIH Clinical Center.

IRP Pushes Forward in Fight Against Pandemic Virus

Many NIH Labs Remain Focused on COVID Research

SARS-CoV-2 virus particles

Since the early days of the COVID-19 pandemic, IRP researchers have been hard at work learning about the virus and developing ways to prevent and treat infections. That research remains as important as ever, particularly as the new Omicron variant of the virus continues to spread rapidly.

Fortunately, NIH’s Intramural Targeted Anti-COVID-19 Program (ITAC) has been providing IRP scientists with millions of dollars to support their research on the pandemic virus, known as SARS-CoV-2. Last week, the “I Am Intramural” blog discussed ITAC-funded efforts to learn about the biology of the virus and how it affects the body. This week, we’ll look at IRP projects focused on ways to track, treat, and prevent infections.

IRP Scientists Continue Efforts to Quell Pandemic

COVID-19 Research at NIH Show No Signs of Slowing

SARS-CoV-2 virus particle

It’s been more than two years since the first outbreak of COVID-19 occurred in China. During that time, amazing scientific advances have dramatically altered prevention and treatment for the illness, including the development of remarkably safe and effective vaccines. However, even with widespread vaccination, scientists predict that the disease will continue to circulate in society indefinitely, with seasonal ebbs and flows like the flu.

As a result, even as COVID-19 vaccine shots rolled out by the hundreds of millions, numerous IRP researchers continued studying the disease and the virus responsible for it. Many of these projects have been funded by the NIH’s Intramural Targeted Anti-COVID-19 Program (ITAC), an initiative that provides IRP researchers with funding for research related to COVID-19. Over the past year and a half, ITAC has provided more than $12 million to support a wide variety of projects — more than can be covered in just one blog post. Read on to learn about just a handful of the many ways IRP researchers are contributing to the fight against COVID-19, and stay tuned next week for another blog describing even more ITAC-funded COVID research.

A New Approach to Male Birth Control

Research in Cells Shows Promise for an Alternative Way to Halt Sperm Production

birth control pills

Birth control has long been mostly one-sided, as the vast majority of contraceptive methods are intended exclusively for women. However, recent IRP research has shown the potential of a new approach towards creating a reversible method of male contraception.

Women have a vast array of contraceptive options available to them, from ‘the pill’ to intrauterine devices (IUDs) and other products. However, for men, the only options aside from condoms are safe but irreversible surgical procedures. More than 40 percent of pregnancies in the U.S. are unintended, and additional options for male birth control could help reduce that number.

A New View of How Muscles Move

IRP Research Challenges Long-Held Ideas About Muscle Structure

sprinter starting to run

It’s not every day an accidental observation overturns 100 years of biological knowledge. But that’s what happened when IRP Stadtman Investigator Brian Glancy, Ph.D., noticed something funny while reviewing high-definition 3D videos of muscle cells.

“To be honest, you could almost call this study an accident,” he says.

Dr. Glancy, who leads the National Heart, Lung, and Blood Institute (NHLBI)’s Muscle Energetics Lab, often uses the high-powered microscopes available through the NHLBI Electron Microscopy Core to study how energy is distributed through skeletal muscle cells — the ones that control voluntary movement — when they expand and contract.

Although he was focused on examining the cells’ energy-producing mitochondria, he could also see the other structures inside them, including the long, tube-like structures called myofibrils that are involved in muscle contraction. As he advanced the video and traveled down the length of the muscle, it looked to him like the myofibrils were changing shape.

Genetic Sequencing Solves Drug Reaction Mystery

Immune System Genes Linked to Severe Side Effects in Patients with Rare Disease

computer monitor showing the results of DNA sequencing

When you run the largest-ever study of a rare childhood disease, you become the go-to person when your peers notice something peculiar in patients with the illness. It was not too surprising, then, when a researcher from Stanford University in Palo Alto, California, asked IRP investigator Michael Ombrello, M.D., to help her team follow a new lead in the mystery of why some patients with a rare inflammatory condition called Still’s disease were coming down with a life-threatening lung ailment. The results of their collaboration could lead to a new precision medicine approach that individualizes therapy for Still’s disease based on patients’ DNA.

Mouse Study Links Anxiety to Neuronal Power Failure

Chronic Stress Diminishes Energy Production in the Brain

unplugged power cord

When power lines come down and the electricity shuts off, it’s understandably a worrying situation. As it turns out, people may become anxious not just when their homes are cut off from energy, but also when their brains find themselves short on power, according to recent IRP research done in mice.

While the misfortune of a blackout is temporary, many people experience chronic stress that bothers them continuously. In some individuals, repetitive stressors can contribute to the development of debilitating anxiety that interferes with everyday life. Intriguingly, past research has found evidence that problems with the biological batteries that power our cells, called mitochondria, might be involved in anxiety disorders, as well as some other psychiatric illnesses.

Duo Delves Into Genetics of Diabetes

Drs. Leslie Baier and Robert Hanson Identify Genetic Risk Factors in American Indians

A team of researchers at NIH’s campus in Phoenix, Arizona, is working with the local American Indian community to learn about genetic risk factors for type 2 diabetes.

November is both Diabetes Awareness Month and Native American Heritage Month. Unfortunately, the month of November is not the only link between Indigenous populations and diabetes. Members of minority groups have a much higher risk of developing type 2 diabetes and its many complications compared to the general population, and this is especially true of some American Indian tribes, whose members are twice as likely to have type 2 diabetes as white Americans.

At the Phoenix Epidemiology and Clinical Research Branch in Arizona, part of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), IRP senior investigators Leslie J. Baier, Ph.D., and Robert Hanson, M.D., M.P.H., are working to understand why American Indians living in the southwestern U.S. are disproportionately affected by type 2 diabetes and obesity. Using family histories, medical records, and other data collected during a decades-long study of these communities, combined with extensive analysis of some of their participants’ DNA, their team has identified several genes that contribute to risk for those two conditions, along with some surprising findings about their prevalence.