Research teams have pinpointed the genomic variants responsible for the rare and debilitating skin disorder known as disabling pansclerotic morphea. This uncommon inflammatory skin disease is characterized by severe skin lesions and a deficiency in wound healing, which results in significant scarring. The researchers discovered that patients afflicted with this disorder have a hyperactive form of the STAT4 protein, a protein instrumental in regulating inflammation and wound healing.
A potential therapeutic avenue using the drug ruxolitinib, which targets the inflammatory pathway, has been identified. This drug, known as a Janus kinase (JAK) inhibitor, was seen to markedly alleviate symptoms in patients.
The disabling pansclerotic morphea disease has a genetic basis, which was exposed through genome sequencing. The research was led by scientists from the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), in collaboration with researchers from the University of California, San Diego (UCSD) and the University of Pittsburgh. The research team also included members from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute of Allergy and Infectious Diseases, both divisions of the NIH.
Disabling pansclerotic morphea, an ailment first mentioned in medical literature approximately a century ago, has only been diagnosed in a few patients. The disorder leads to severe skin lesions, poor wound healing, and deep scarring across all layers of the skin and muscles, culminating in the hardening and degradation of muscles and stiffening of joints. This progression significantly restricts mobility. The genetic cause of this rare disorder has been undiscovered until this point.
The research team used genome sequencing to study four individuals with disabling pansclerotic morphea and discovered that all four possess genomic variants in the STAT4 gene. This gene produces a protein that activates and deactivates genes, known as a transcription factor, which plays a pivotal role in combating infections and supervising wound healing in the skin.
The identified STAT4 genomic variants result in an overactive STAT4 protein in the patients, establishing a damaging cycle of inflammation and impaired wound healing that escalates with time. The team managed to break this harmful cycle by targeting another protein interacting with the STAT4 molecule in the inflammatory pathway, Janus kinase or JAK. Upon treating the patients with ruxolitinib, a JAK-inhibiting drug, their rashes and ulcers markedly improved.
Existing treatments for disabling pansclerotic morphea have aimed to halt disease progression, but past therapies have generally been ineffective and associated with severe side effects. Typically, patients with this disorder do not survive more than a decade post-diagnosis.
Ruxolitinib, a member of the broader class of drugs known as JAK inhibitors, is proposed as an effective treatment for this disorder. JAK inhibitors are commonly used to treat chronic inflammatory diseases such as arthritis, eczema, ulcerative colitis, and others.
This study’s findings hint at the possibility of JAK inhibitors being a potential treatment for other inflammatory skin disorders or disorders related to tissue scarring, like scarring of the lungs, liver, or bone marrow. The researchers aim to continue studying this pathway and how it is altered in patients with disabling pansclerotic morphea and related conditions to gain insights into a broader range of more prevalent diseases.
The results of this research have been published in the New England Journal of Medicine.
Reference: “Variant STAT4 and Response to Ruxolitinib in an Autoinflammatory Syndrome” by a diverse team of scientists, May 31, 2023, New England Journal of Medicine. DOI: 10.1056/NEJMoa220
Table of Contents
What is the rare skin disorder discussed in the text?
The rare skin disorder discussed in the text is disabling pansclerotic morphea. It is characterized by severe skin lesions, poor wound healing, and deep scarring across all layers of the skin and muscles. The disorder causes the muscles to harden and break down, while the joints stiffen, leading to reduced mobility.
Who conducted the research on disabling pansclerotic morphea?
The research was conducted by a team of scientists from the National Human Genome Research Institute (NHGRI), a part of the National Institutes of Health (NIH). Collaborators included researchers from the University of California, San Diego (UCSD), and the University of Pittsburgh. Researchers from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute of Allergy and Infectious Diseases, both divisions of NIH, also participated in the study.
What significant discovery did the researchers make?
The researchers discovered that patients with disabling pansclerotic morphea have genomic variants in the STAT4 gene. This gene produces an overactive version of the STAT4 protein that initiates a harmful cycle of inflammation and impaired wound healing. They have also found a potential treatment option using the drug ruxolitinib, a Janus kinase (JAK) inhibitor, which can break this harmful cycle and dramatically improve symptoms.
Is the drug ruxolitinib already available?
As of the time of this text, it’s not explicitly stated whether ruxolitinib is commercially available specifically for the treatment of disabling pansclerotic morphea. However, ruxolitinib is a part of a broader class of drugs known as JAK inhibitors, which are commonly used to treat chronic inflammatory diseases such as arthritis, eczema, and ulcerative colitis.
Could the findings from this study be applied to other disorders?
Yes, the findings from this study suggest that JAK inhibitors like ruxolitinib could potentially be used to treat other inflammatory skin disorders or disorders related to tissue scarring. Future research will explore these possibilities.
Related links:
- National Institutes of Health (NIH)
- National Human Genome Research Institute (NHGRI)
- Disabling Pansclerotic Morphea: Rare Disease Database
- Information on Ruxolitinib: MedlinePlus
- Information on Janus Kinase (JAK) inhibitors: Mayo Clinic
7 comments
Wow, it’s really amazing what these scientists are doing, they’re literally changing lives!
That’s so encouraging, finally a hope for people suffering from this rare skin disorder! keep up the good work.
Is this drug already available or still in testing? Hope it gets to the patients soon.
wonder how many people actually have this disease? It says its rare… also hope the drug doesnt have any bad side effects
Incredible what genome sequencing can do these days! they find a cause and a potential cure…science is awesome.
The research sounds promising, the fact they are already treating people is a good sign, keep it up docs!
So sad to hear people suffering with such a condition… Glad science is advancing to help them out!