accomplishments

Rare Genetic Mutation Links Two Neurological Diseases

Globe-Spanning Collaboration Connected ‘Viking Gene’ to Dementia and ALS

A man with ALS uses a head-mounted laser pointer to communicate with his wife by pointing to letters and words on a communication board

June was an important month in the life of baseball great Lou Gehrig. It was the month he was born and the month he was first picked for the Yankees’ starting lineup. Sadly, it was also the month in 1939 when he was diagnosed with the neurological disease that bears his name — Lou Gehrig’s disease, also known as amyotrophic lateral sclerosis (ALS) — and the month he died of that disease two years later. It is appropriate then that ALS Awareness Day is observed on June 21 as a day of hope for those searching for effective treatments and, ultimately, a cure.

IRP senior investigator Bryan J. Traynor, M.D., Ph.D., a neurologist at the National Institute on Aging (NIA), is one of the people leading that search. Best known for his work unraveling the genetic causes of ALS and frontotemporal dementia (FTD), he led an international consortium of researchers that uncovered a mutation on chromosome 9 that is the most common ‘familial’ cause of both ALS and FTD. In fact, this mutation, which disrupts the function of the C90RF72 gene, is responsible for 40 percent of all familial cases of ALS and FTD in European and North American populations, meaning cases in which a family member also has the disease. The discovery, published in 2011, revolutionized the scientific understanding of neurodegenerative diseases and the relationships between them. It also suggested a potential target for future gene therapies.

A Ray of Hope for a Rare and Deadly Skin Cancer

IRP Research Leads to First FDA-Approved Therapy for Merkel Cell Carcinoma

Dr. James Gulley talking with a patient

May is Skin Cancer Awareness Month. Skin cancers are the most common cancer in the U.S., affecting as many as five million people every year. Yet the rarest of these cancers is also one of the deadliest. Merkel cell carcinoma affects about 3,000 Americans each year, and until recently a lack of effective treatments meant only half of patients survived five years or longer after diagnosis. The median survival was nine months.

This bleak outlook changed radically in 2017 with the US Food and Drug Administration (FDA) approval of a new immunotherapy drug called avelumab. Developed through a collaboration between IRP researchers and the pharmaceutical company EMD Serono, Inc., and marketed as Bavencio, avelumab was the first treatment approved specifically for Merkel cell carcinoma.

How a Marker for Genetic Damage Changed the Study of DNA

Decades Later, IRP Researcher’s Discovery Is Used in Labs Around the World

Dr. William Bonner

National DNA Day, held on April 25, commemorates the completion of the Human Genome Project in 2003 and the day in 1953 when a research team led by Drs. James Watson, Francis Crick, Maurice Wilkins, and Rosalind Franklin published their groundbreaking paper on the structure of DNA in the journal Nature.

The mapping of DNA’s structure opened the door to modern genetics and our current understanding of how DNA affects the health and survival of all living things. Since then, there have been numerous additional major leaps forward in the field of genetics. Among them was the discovery of a universal hallmark of DNA damage by IRP Scientist Emeritus William Bonner, Ph.D., an advance that revolutionized the study of how cells sense and repair genetic defects. Dr. Bonner’s findings paved the way for a deeper understanding of cell biology, as well as clinical advances for treating cancer and for assessing risks from radiation in the environment.

NIH Scientists Redesign Neurons to Enable Targeted Therapies

New Receptors and Radioactively Labeled Molecules Could Provide Useful Tools for Research and Medicine

neurons firing

Genetically modifying neurons to enable scientists and clinicians to influence brain activity probably sounds like the stuff of science fiction. However, the technology has existed for more than a decade, allowing scientists to make important leaps in understanding how neurons communicate with one another in healthy individuals and those with psychological and neurological conditions. What’s more, recent improvements to these tools developed by researchers led by IRP investigator Mike Michaelides, Ph.D., may allow neurologists to use them to deliver drugs to just the right brain cells to treat those ailments effectively without the side effects caused by current treatments.

Designer Drug Uses Double Whammy to Fight Heart Disease

Custom-Built Molecule May Improve On Its Natural Counterpart

plaque buildup in an artery

Ten years ago, a young woman from Chicago came to the National Institutes of Health with a rare genetic condition. A mutation in her DNA was making her metabolic system malfunction, causing levels of fat molecules called triglycerides in her blood to skyrocket far out of the normal range. This triggered inflammation in her pancreas, a painful and potentially life-threatening condition known as pancreatitis. She couldn’t understand why there wasn’t any kind of treatment to help her.

IRP senior investigator Alan T. Remaley, M.D., Ph.D., took on the challenge with the help of Anna Wolska, Ph.D., a research fellow in his lab. Dr. Remaley leads the Lipoprotein Metabolism Section in the National Heart, Lung, and Blood Institute (NHLBI), where he and Dr. Wolska study lipoproteins, small particles that transport fats such as cholesterol and triglycerides through the bloodstream to be broken down and used by cells for energy. Their efforts to help that young woman ultimately led to the discovery — published last January — of a new strategy for reducing triglycerides in order to treat serious ailments like pancreatitis and heart disease.

A Sweet Treatment for Diabetes

Sugar Molecule Protects Mice Against Type 1 Diabetes

a spoonful of sugar

Avoiding too much sugar is one of the cardinal rules for those who have or are at risk for diabetes. In fact, diabetes is characterized by having too much glucose, a form of sugar, in the blood. As a result, it came as quite a surprise to IRP researchers led by senior investigator Wanjun Chen, M.D., when they discovered that a particular form of sugar that they expected to have no effect on diabetes-prone mice actually protected them from developing type 1 diabetes.

Closing in on the Circuitry of Chronic Itch

Genetic Studies Illuminate Neuronal Chemical’s Role in Pain and Itch

hands with rash caused by psoriasis

For most of us, itch is a bothersome inconvenience. Unfortunately, for 125 million people around the world, chronic itch caused by the skin disease psoriasis is a significant, even debilitating, health problem. Psoriasis causes skin cells to multiply up to 10 times faster than normal and build up as an itchy and painful, scaly rash. For some, the condition can also cause joint swelling, resulting in a condition known as ‘psoriatic arthritis.’

World Psoriasis Day falls on October 29 this year, and the theme is “Be Informed.” So, what do we know about chronic itch?

Mouth Microbes Turn Treasonous in Gum Disease

Four Questions with Dr. Niki Moutsopoulos

bacteria

Our mouths are teeming with bacteria, a microbial ecosystem known as the oral microbiome. While these microbes are typically benign, under certain circumstances they can turn harmful and contribute to oral diseases such as periodontitis, a form of chronic gum disease characterized by microbe-driven inflammation of the soft tissues and bone that support our teeth. According to the Centers for Disease Control and Prevention (CDC), roughly 65 million Americans aged 30 or older have some degree of periodontitis. In its early stage, known as gingivitis, the gums become swollen and red due to inflammation, which is the body’s natural response to the presence of bacteria. If the condition worsens, it can lead to loose teeth and, eventually, bone or tooth loss.

NIH senior investigator Niki Moutsopoulos, Ph.D., head of the Oral Immunity and Inflammation Section at the National Institute of Dental and Craniofacial Research (NIDCR), studies periodontitis and aims to understand the immune system’s role in driving this destruction. In a 2018 study, she and her team of IRP researchers and outside collaborators discovered that an abnormal and unhealthy population of microbes in the mouth causes specialized immune cells, known as T helper 17 (Th17) cells, to trigger inflammation and destroy tissue, leading to periodontitis.

Extreme Obesity Shaves Years Off Life Expectancy

Four Questions with Dr. Cari Kitahara

a man with obesity walking in the park

As happens with every new year, many people around the world woke up on January 1 committed to improving their health through eating well and exercising. These lifestyle changes have the potential to significantly improve the well-being of the 32 percent of American adults who are overweight and the 40 percent who are obese. Due to the staggering number of individuals struggling with obesity, as well as its serious health consequences, the condition has long been a main priority for researchers at the NIH. As a result of this focus, investigators have made significant strides in identifying biological signals that trigger hunger, understanding genetic influences that play a role in weight gain, and uncovering environmental and behavioral factors that influence obesity.

Three-Armed Antibody Could Offer Defense Against AIDS

Four Questions with Dr. John Mascola

HIV-infected T cell

The disease known as human immunodeficiency virus, or HIV, attacks and destroys cells vital to the immune system. This leaves the millions of people living with HIV less able to fight other infections and can lead to an extremely severe form of immune system deficiency called acquired immunodeficiency syndrome (AIDS), which was responsible for nearly 770,000 deaths in 2018 alone. As of 2019, there are approximately 37.9 million people around the world living with HIV/AIDS.

Although HIV/AIDS has been recognized as a serious public health crisis, finding effective treatments, or a vaccine to prevent infection in the first place, is not a simple task. The HIV virus has many different types and strains — similar to the flu — which makes developing vaccines and treatments extremely challenging, as the virus is constantly changing. At the NIH, there are a number of ongoing collaborative research projects aimed at providing new options for those diagnosed with HIV/AIDS and those at risk for contracting the virus in the future.