From the journals

BLOCKING AN ALZHEIMER’S CATALYST

Tau proteins in the brain that undergo harmful, inflammation-driven changes—including a process known as phosphorylation—are a hallmark of Alzheimer’s disease. In research published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions in October 2023, an experimental drug called 2-MPPA, synthesized by the Johns Hopkins Drug Discovery Program, reduced levels of toxic tau. “We were able to reduce the phosphorylation of tau by restoring regulatory actions that are lost with age and inflammation,” said senior author Amy Arnsten, PhD, Albert E. Kent Professor of Neuroscience and professor of psychology. The researchers now aim to develop similar drugs for use in humans.

TYPE 1 DIABETES DRUG PRESERVES BETA CELL FUNCTION

In research led by Kevan Herold, MD, C.N.H. Long Professor of Immunology and of Medicine (Endocrinology), the drug teplizumab, a monoclonal antibody, was shown to preserve the function of beta cells in children and adolescents recently diagnosed with type 1 diabetes. This finding, published in The New England Journal of Medicine in December 2023, followed the FDA’s 2022 approval of teplizumab (Tzield®). The approval was based on the results of an earlier Herold-led trial, which showed that the drug delays the onset of stage 3 type 1 diabetes. Teplizumab is the first treatment to alter the course of this autoimmune disease since the discovery of insulin in 1922.

GENETIC BASIS OF CANNABIS USE DISORDER

In a study published in Nature Genetics in December 2023, researchers analyzed the genomes of more than 1 million people to investigate the genetic basis of cannabis use disorder, as well as links to psychiatric disorders and other traits related to substance use. The research, led by Daniel Levey, PhD, assistant professor of psychiatry, and Joel Gelernter, MD, Foundations Fund Professor of Psychiatry and professor of genetics and of neuroscience, will help in the understanding of the public health risks associated with the continuing legalization of marijuana use across the United States, Gelernter said.

INVESTIGATING DISEASE PATHOGENESIS IN ATAXIA

Spinocerebellar ataxia type 1 is a neurodegenerative disorder that primarily affects the cerebellum, a brain region involved in the control and coordination of movements. The disease ultimately robs patients of their ability to walk properly. Janghoo Lim, PhD, associate professor of genetics and neuroscience, and colleagues used single-nucleus RNA sequencing to determine how gene expression changes within specific types of cerebellar cells throughout the course of the disease. These results, published in Neuron in November 2023, illuminate the cellular and molecular basis of this disease. The Yale researchers are the first to study changes in gene expression in the postmortem tissues of patients with ataxia at the level of single-cell resolution.

IMPROVING RECOVERY AFTER ICU CARE

In the first few months after receiving ICU care for a critical illness, such as sepsis, older adults suffered a threefold increase in symptoms like shortness of breath, fatigue, and others that restricted their activity and threatened their quality of life, according to a study published in the American Journal of Respiratory and Critical Care Medicine (December 2023). The study emphasized that the first month following ICU hospitalization is a critical time for such interventions as medications and exercise. These measures could improve patients’ recovery and prevent hospitalizations, said lead author Snigdha Jain, MD, MHS, assistant professor of medicine (pulmonary, critical care, and sleep medicine).

EQUITABLE TREATMENT FOR SICKLE CELL DISEASE

Gene therapy, recently approved by the FDA to treat sickle cell disease (SCD), could be an equity-enhancing treatment, according to research conducted by George Goshua, MD, MSc, assistant professor of medicine (hematology), and his colleagues. Although the gene therapy, projected to cost $2.45 million, did not meet traditional cost-effectiveness standards, it did satisfy distributional cost-effectiveness standards—an approach that takes health equity into quantitative consideration. In the United States, SCD primarily affects historically marginalized patient populations. The research was published in the Annals of Internal Medicine in May 2023.