Findings could lead to new scleroderma treatment, researchers say by Steve Bryson, PhD | April 15, 2025

​Exosomes, tiny sacs containing biomolecules secreted from stem cells, thinned skin scarring in a mouse model of scleroderma, as well as skin samples from patients, a study reported.
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These findings support “the use of exosomes as a clinical treatment for [scleroderma] skin fibrosis,” the researchers said in the study, “Exosomes carrying adipose mesenchymal stem cells function alleviate scleroderma skin fibrosis by inhibiting the TGF-β1/Smad3 axis,” which was published in Scientific Reports.

Scleroderma is an autoimmune disorder marked by the abnormal accumulation of collagen, the main protein component of scar tissue, in the skin and various organs. It’s called localized scleroderma when it affects just the skin and/or underlying muscle tissue, and systemic scleroderma when organs, including the heart, lungs, stomach, and kidneys, are also involved.
Nearly all scleroderma patients have skin involvement, and the severity of skin scarring, or fibrosis, is typically associated with damage to the vital organs and mortality.

Mesenchymal stem cells, or MSCs, are a type of stem cell found in various tissues, including the bone marrow, adipose (fat) tissue, and the umbilical cord. Due to their anti-fibrotic and anti-inflammatory properties, MSCs have been considered a promising treatment for scleroderma.
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MSCs work by releasing signaling proteins and/or exosomes, tiny membrane-bound sacs that carry proteins and other molecules important for cellular communication. Because exosomes are cell-free, they may circumvent the adverse effects associated with MSC therapy, including immune rejection.

Car T-cell therapy aims for off-shelf cell supply by Marisa Wexler, MS | April 8, 2025

The U.S. Food and Drug Administration (FDA) has granted fast track designation to the cell therapy ALLO-329 to treat active refractory (resistant to treatment) diffuse scleroderma, also known as diffuse systemic sclerosis (SSc).

The FDA also gave ALLO-329 fast track designation as a potential treatment for two other inflammatory diseases: myositis, which is characterized by muscle inflammation, and lupus, which is marked by antibodies that attack the body’s healthy tissues.

Fast track designation is designed to speed the development of new treatments that have the potential to address unmet medical needs for serious or life-threatening diseases. With these designations, ALLO-329’s developer Allogene Therapeutics will get access to benefits including more frequent interactions with the FDA throughout the drug development process.

“Receiving these designations for ALLO-329 underscores the versatility and transformative promise of this next-generation allogeneic CAR T investigational product in redefining the autoimmune treatment landscape,” said Zachary Roberts, MD, PhD, executive vice president of research and development and chief medical officer of Allogene, said in a company press release.
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ALLO-329 is a CAR T-cell therapy. T-cells are immune cells that are able to kill other types of cells. CAR T-cell treatments involve engineering T-cells to equip them with a chimeric antigen receptor (CAR), a molecular weapon that directs a T-cell to attack other cells bearing specific molecular markers. ALLO-329 uses a CAR that targets CD19 and CD70, two proteins that are present, respectively, on the surface of B-cells and T-cells, both of which are immune cells involved in the development of many autoimmune diseases.

I like to go for walks when it's not too hot or cold by Tomisa Starr | April 2, 2025

For those of us with scleroderma, it’s important to stay warm, because changes in body temperature, especially when exposed to the cold, can cause blood vessels to constrict.

I like to go for walks to get exercise and maintain my lung function. My exercise “Goldilocks zone” — my favorite time of the year to go for walks — is when it’s not too cold or hot outside. Where I live in California, that occurs from late fall to spring, when the daily high temperatures are in the mid 50s to 60s. Exercise makes my blood flow, which helps to keep me warm.
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Raynaud’s phenomenon, a condition where the fingers and toes feel numb, prickly, and frigid in response to cold temperatures or stress, is common among people with scleroderma. The constriction of blood vessels can cause color changes in the fingers. My fingers look purple, yellow, and red when Raynaud’s affects me.

Sustained slowing of lung function decline shown for SSc-ILD patients
by Andrea Lobo, PhD | March 25, 2025

Treatment with Ofev (nintedanib) for up to four years was associated with a sustained slowing of lung function decline in people with systemic sclerosis (SSc) associated with interstitial lung disease (SSc-ILD).

That’s according to new results from the open-label study SENSCIS-ON (NCT03313180), a three-year extension of the SENSCIS Phase 3 trial that formed the basis for the therapy’s regulatory approvals. In the long-term extension, Ofev also had a safety profile consistent with previous studies, the new data show.
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“These findings suggest that [Ofev] can be used over the long term to slow the progression of SSc-ILD and so improve patient outcomes,” the researchers wrote.
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Their study, “Continued nintedanib in patients with systemic sclerosis-associated interstitial lung disease: 3-year data from SENSCIS-ON,” was published as a brief report in the journal RMD Open Rheumatic & Musculoskeletal Disorders.

Safety study testing ADI-001 in adults with various autoimmune diseases
by Margarida Maia, PhD | March 18, 2025

Adicet Bio expects adults with systemic sclerosis (SSc) soon to start enrolling in its ongoing Phase 1 clinical trial of ADI-001, an experimental CAR T-cell therapy that the company is developing for a number of autoimmune diseases.

The company had expected sites to open to SSc patients before the end of last year, and now anticipates recruitment to be underway by the close of June. The open-label Phase 1 clinical trial (NCT06375993) currently is continuing to enroll adults with lupus nephritis, a common complication of the autoimmune disease lupus.

Depending on the speed with which people with SSc are enrolled, preliminary data on treated patients might be available toward the close of 2025.

ADI-001 targets B-cells, aiming to prevent damaging immune system attacks
ADI-001 recently received fast track status in the U.S. for treating adults with SSc, which works to speed the development and review of therapies for serious diseases with an unmet need.

This designation “highlights the significant unmet need for innovative, off-the-shelf therapies to treat autoimmune diseases,” Chen Schor, president and CEO of Adicet Bio, said in a company press release reporting on last year’s financial results and recent progress.

Systemic sclerosis, also called systemic scleroderma, is a multisystem autoimmune disease marked by the accumulation of scar tissue in the skin and organs that can include the heart, kidneys, lungs, and digestive tract.

Autoimmune diseases like SSc occur when the immune system produces antibodies that mistakenly react against healthy tissues in the body, guiding a damaging immune attack. Antibodies, including self-reactive ones, are produced by immune B-cells.

ADI-001 involves collecting a patient’s immune T-cells and modifying them in the lab before returning them via an infusion. T-cells are modified such that they produce a chimeric antigen receptor, or CAR, that binds to CD20, a protein found on the surface of B-cells.

Most of the T-cells present in ADI-001 are of a subtype called gamma delta T-cells, which naturally target various tissues, according to the company. Once CAR T-cells bind to CD20, they are activated to destroy B-cells, as reported in early clinical data from people with B-cell cancers, another indication for which the therapy is being developed.
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By killing B-cells, ADI-001 is expected to reduce the production of self-reactive antibodies, easing symptoms in people with autoimmune diseases.

Patients also had abnormal levels of heart damage marker BNP, uric acid
by Andrea Lobo, PhD | March 4, 2025

Low levels of a type of white blood cell called natural killer (NK) cells may help diagnose pulmonary arterial hypertension (PAH) in people with systemic sclerosis (SSc), a study in China suggests.

In PAH, the blood vessels that supply blood to the lungs, called pulmonary arteries, narrow, restricting blood flow and raising blood pressure. In the study, about 28% of the SSc patients had PAH.

Abnormal levels of BNP, a marker of heart damage, and of uric acid, which is an indicator of lower kidney function, were also evident in SSc-PAH patients.

“These indicators can aid in evaluating disease activity and pulmonary hypertension incidence in SSc,” wrote the researchers, who noted that while the markers have “clinical value for diagnosing PAH … their independent diagnostic utility for SSc-PAH remains suboptimal.” The study, “Natural killer cells are decreased in systemic sclerosis and have diagnostic value for pulmonary arterial hypertension incorporation,” was published in Scientific Reports.

SSc is marked by inflammation and fibrosis, or the accumulation of scar tissue, in the skin and even the internal organs, including the lungs. PAH is a leading cause of death in SSc, also called scleroderma.
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The disease mechanisms involve autoimmune, or self-reactive, processes and abnormal inflammatory responses. Immune NK cells have been implicated in other autoimmune diseases and have shown alterations in people with SSc.

Acid reflux, depression symptoms also contributed to poor experience by Patricia Inácio, PhD | February 25, 2025

​People with systemic sclerosis (SSc) face significantly worse sleep quality than those with rheumatoid arthritis (RA) and healthy people, a study reports.
Poor sleep hygiene and clinical factors, including gastroesophageal reflux disease, that is, acid reflux, and depression-like symptoms, were key contributors.

These findings highlight how “enhancing sleep hygiene practices may serve as a crucial strategy to improve the overall sleep quality in SSc,” the researchers wrote. The study, “Inadequate sleep hygiene as a key factor in poor sleep quality in systemic sclerosis: an observational, cross-sectional study,” was published in Rheumatology International.

In SSc, also called scleroderma, scar tissue accumulates in the skin and also can in internal organs, including the heart, kidneys, lungs, and digestive tract. Sleep impairments are known to be high among people with SSc and RA, also an autoimmune disorder.

Here, researchers in Turkey evaluated how sleep hygiene — the collection of lifestyle, environmental, and behavioral strategies for healthy sleep habits — influences sleep quality and correlates with clinical parameters in SSc patients.

​They also compared sleep hygiene and sleep quality between people with SSc, those with RA, and healthy people, who served as controls. Each group was composed of 70 age-matched participants, all female. The median age in the SSc group was 52.7.

Staying aware of my body and the signals it may be giving me is crucial by Tomisa Starr | February 19, 2025

As we get older, how can we tell the difference between the effects of aging and the symptoms and comorbidities related to scleroderma?

When most people think of scleroderma, aging with the disease doesn’t immediately come to mind. When I first read about it in 1974, patients with the disease had far fewer treatment options than they do today. That’s changed, thankfully, and we’re now likely to survive for a longer time.

My diagnosis came when I was a 30-year-old wife and mother. My rheumatologist told me the disease could affect every organ in the body, and she was concerned that my case seemed to be progressing fast. Beyond the physical, it’s not uncommon for people to experience fear and anxiety with any serious illness, and I did.
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But over 30 years later, here I am, a senior citizen with scleroderma.

Primary heart involvement is a common complication of systemic sclerosis by Margarida Maia, PhD | February 11, 2025

Immunosuppressive medications may help to reduce inflammation in the heart and the overall burden of primary heart involvement that is associated with systemic sclerosis (SSc), a retrospective study suggests.

Larger studies are needed to confirm these findings, its researchers stated.
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The study, “Immunosuppressive therapy to treat newly diagnosed primary heart involvement in patients with systemic sclerosis: An Italian cardiac magnetic resonance based study,” was published in Seminars in Arthritis and Rheumatism.

Researchers used machine learning algorithms to analyze data
by Margarida Maia, PhD | February 4, 2025

​The CCL2 gene, which codes for a signaling protein of the same name, is “a common characteristic gene” of both systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF), a serious complication of SSc that causes the lungs to become inflamed and scarred, according to a study by researchers in China.

“We identified CCL2 as a common biomarker from IPF and SSc, revealing the common mechanism of these two diseases,” the researchers wrote in “Common biomarkers of idiopathic pulmonary fibrosis and systemic sclerosis based on WGCNA and machine learning,” published in the journal Scientific Reports.

According to the researchers, their study provides “clues for the study of the treatment and mechanism of these two diseases.” However, these findings need to be confirmed by lab and clinical testing, given that the study “used data from a public database and lacked support from clinical data,” in addition to other limitations, the team noted.
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The researchers used machine learning algorithms, a type of artificial intelligence, to analyze the data from that database.