Scientists find treatment for rare genetic skin disorder (Ruxolitinib helps disabling pansclerotic morphea)

Medical Xpress / NIH/National Human Genome Research Institute / New England Journal of Medicine ^ | May 31, 2023 | Dan Kastner, M.D., Ph.D. et al

[ConservativeMind]

Researchers have identified genomic variants that cause a rare and severe inflammatory skin disorder, known as disabling pansclerotic morphea, and have found a potential treatment.

Scientists discovered that people with the disorder have an overactive version of a protein called STAT4, which regulates inflammation and wound healing. The work also identified a drug that targets an important feedback loop controlled by the STAT4 protein and significantly improves symptoms in these patients.

Only a handful of patients have been diagnosed with disabling pansclerotic morphea, a disorder first described in the medical literature around 100 years ago. The disorder causes severe skin lesions and poor wound healing, leading to deep scarring of all layers of the skin and muscles. The muscles eventually harden and break down while the joints stiffen, leading to reduced mobility. Because the disorder is so rare, its genetic cause had not been identified until now.

The scientists found that the STAT4 genomic variants result in an overactive STAT4 protein in these four patients, creating a positive feedback loop of inflammation and impaired wound-healing that worsens over time. To stop this harmful feedback loop, they targeted another protein in the inflammatory pathway that interacts with the STAT4 molecule and is called Janus kinase, also known as JAK. When the researchers treated the patients with a JAK-inhibiting drug called ruxolitinib, the patients' rashes and ulcers dramatically improved.

People with the disorder typically don't live more than 10 years after their diagnosis.

The study suggests that ruxolitinib could be an effective treatment for patients with this disorder. Ruxolitinib is part of a broader class of drugs called JAK inhibitors, which are commonly used to treat arthritis, eczema, ulcerative colitis and other chronic inflammatory diseases.

[ConservativeMind]

This therapy (ruxolitinib) could help multiple other tissue scarring conditions, they claim.

[ConservativeMind]

The “Take Charge Of Your Health” Ping List
This high volume ping list is for health articles and studies which describe something you or your doctor, when informed, may be able to immediately implement for your benefit.

Email me to get on either the “Common/Top Issues” (20 - 25% fewer pings) or “Everything” list.