Discoveries & Innovations: NIH Finds First Treatment for Rare Skin Disorder
Disabling pansclerotic morphea (DPM) is a rare and poorly understood genetic skin disorder that causes severe skin lesions and poor wound healing, resulting in scarring of skin and muscle tissue and often long-term reduced mobility as muscles eventually harden and break down and the joints stiffen. Patients with the disorder typically don’t live more than 10 years after their diagnosis.
Now, NIH scientists from the National Human Genome Research Institute (NHGRI) and their partner researchers have identified genomic variants that cause the disorder and in doing so, uncovered a treatment option. The studies found an overactive version of a protein called STAT4, which is responsible for regulating inflammation and wound healing, in those who suffer from morphea, as well as a drug that targets the STAT4 feedback loop to improve morphea symptoms in patients.
Sarah Blackstone, a predoctoral fellow within NHGRI’s Inflammatory Disease Section, a medical student at the University of South Dakota, and co-first author of the study, stated in a press release, “Researchers previously thought that this disorder was caused by the immune system attacking the skin. However, we found that this is an oversimplification, and that both skin and the immune system play an active role in DPM.”
The STAT4 gene variants found in the morphea patients causes a constant positive feedback loop for the protein, increasing inflammation constantly, and impairing the entire wound healing process. To stop this positive feedback loop, the researchers targeted Janus kinase, or JAK, which interacts with STAT4. When the research team treated their four morphea patients with a JAK-inhibiting drug called ruxolitinib, the patients’ rashes and ulcers dramatically improved.
This rare disease has hardly any existing treatment options and those that do exist have not proved effective or improved the fatality of the disease. “The findings of this study open doors for JAK inhibitors to be a potential treatment for other inflammatory skin disorders or disorders related to tissue scarring, whether it is scarring of the lungs, liver, or bone marrow,” stated Dan Kastner, MD, PhD, Head of NHGRI’s Inflammatory Disease Section, and a senior author of the paper.
Doctor Docs: Physicians Finally Get Some Long COVID Data
A large-scale, NIH-funded study is shedding light on the symptoms, details, and best ways to diagnose long COVID. Initial findings from the study of nearly 10,000 Americans, many of whom were infected with COVID-19, find that post-infection conditions can effect early every organ of the body and last for years. Those most affected by long COVID are patients who were infected before the 2021 Omicron variant was identified.
The NIH coordinated the “Researching COVID to Enhance Recovery (RECOVER)” initiative in order to understand why some people develop long-term symptoms following COVID-19, and most importantly, how to detect, treat, and prevent long COVID. Researchers identified 12 symptoms that are most indicative of long COVID when compared to someone without long COVID, these being post-exertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, heart palpitations, issues with sexual desire or capacity, loss of smell or taste, thirst, chronic cough, chest pain, and abnormal movements.
The team developed a scoring system based on combinations of these symptoms and found subgroups of long COVID based on symptoms that often occur together. Surveys of study participants are helping determine the longevity and prevalence of long COVID, including those infected by variants that circulated at different times.
“This study is an important step toward defining long COVID beyond any one individual symptom,” said study author Leora Horwitz, MD, Director of the Center for Healthcare Innovation and Delivery Science, and co-principal investigator for the RECOVER Clinical Science Core, at NYU Langone Health. “This approach—which may evolve over time—will serve as a foundation for scientific discovery and treatment design.”
In addition to the preliminary scoring system, researchers found evidence that participants who were unvaccinated or who had COVID-19 before the Omicron strain emerged in 2021 were more likely to have long COVID and more severe cases of long COVID. Reinfections were also linked to higher long COVID frequency and severity, compared to people who only had COVID-19 once.
“While the score developed in this study is an important research tool and early step toward diagnosing and monitoring patients with long COVID, we recognize its limitations,” David C. Goff, MD, PhD, epidemiology lead for NIH RECOVER, said in a statement. “All patients suffering from long COVID deserve the attention and respect of the medical field, as well as care and treatment driven by their experiences. As treatments are developed, it will be important to consider the complete symptom profile.”
Med Device Department: A Wearable Can Ease Chemo-Caused Nerve Pain
Chemotherapy often causes peripheral neuropathy, which means pain, tingling, burning, weakness, and overall discomfort in the legs throughout and for months following a patient’s treatment. It affects 30% to 60% of people who undergo neurotoxic chemotherapy and occurs when cancer treatments damage the nerves beyond the brain and spinal cord.
NueroMetrix’s Quell is a wearable that is already FDA approved to relieve chronic pain from fibromyalgia and is now in clinical trials to determine its effectiveness in mitigating chemo-induced peripheral neuropathy. The one-of-a-kind device is a neuromodulation system worn as a sleeve around the upper calf. The small sleeve contains electrodes that stimulates sensory nerves in the legs and triggers a pain rely response from the body, which has been successful in treating patients with general chronic leg pain in the past. Patients can use the Quell device on their own for regular treatment with the help of a connective smartphone app.
Current clinical trials for mitigating chemo-induced peripheral neuropathy require patients to use the device for three one-hour sessions every day for six weeks and 11.6% said this improved their quality of life. While the FDA has not yet approved the system for chemo-induced leg pain, study results are promising with Quell users reporting a 50% decrease in hot/burning pain, sharp/shooting pain, and cramping compared to the 30% experienced by placebo groups.
FDA Update
Drug Approvals
Last month, the FDA approved the first two vaccines for older adults against respiratory syncytial virus (RSV). First, GSK received the green light with Arexvy, approved for adults 60 years of age and older. The respiratory syncytial virus vaccine, adjuvanted, prevents lower respiratory tract disease (LRTD) caused by RSV with a statistically significant and clinically meaningful overall efficacy of 82.6%. Pfizer’s Abrysvo, also intended for adults 60 and older, was approved just weeks later. This vaccine is unadjuvanted, a bivalent RSV prefusion F (RSVpreF) vaccine composed of two preF proteins selected to optimize protection against RSV A and B strains. After years of research, the breakthrough vaccines are rushing to market to combat this common and contagious disease that the CDC says sends approximately 177,000 people to the hospital with an estimated 14,000 deaths in the U.S. in adults aged 65 years and older each year. While the vaccines are FDA approved, neither can be used until the CDC makes appropriate recommendations for usage after convening this June.
The FDA granted AstraZeneca approval for Lynparza (olaparib) with abiraterone and prednisone (or prednisolone) for adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC). The treatment requires an FDA-approved companion diagnostic test. Lynparza is most commonly recommended at a 300 mg dose taken twice orally with abiraterone and prednisone for prostate cancer patients.
Med Device Approvals
Medtronic received the FDA go-ahead for its next-generation Micra leadless pacemakers, now with 40% more battery life compared to earlier Micra devices. The Micra AV2 and Micra VR2 miniature, leadless pacemakers now last 16 to 17 years. The AV2 boasts advanced algorithms that automatically program AV synchrony, thereby coordinating the heart’s upper and lower chambers, as well as a higher available tracking capability for faster heart rates in those who are active.
