New study flags existing medications as possible scleroderma treatments
Genetic data analysis highlights candidates for future trials
Written by |
Through an analysis of genetic data, scientists have identified dozens of existing medications that could potentially be repurposed as treatments for scleroderma, according to a new study.
Potential treatments identified in the analysis include therapies that modulate the activity of estrogen, a female sex hormone, as well as medicines that act on inflammatory pathways or neurotransmitters — signaling molecules that nerve cells use to communicate with each other and the rest of the body.
Researchers noted that further work is needed to validate these findings, and that the identified drugs are not immediately ready for repurposing, but said their analysis offers a starting point for identifying existing medications that might be explored for scleroderma.
The study, “Advancing drug development for systemic sclerosis by prioritising findings from human genetic association studies,” was published in Rheumatology.
Study uses genetic data to identify potential drug targets
Scleroderma is marked by inflammation and fibrosis (scarring) that can affect organs throughout the body. Developing effective treatments has been a challenge for scientists, in part because the disease is rare and may affect patients very differently. Recently, cell-based strategies have emerged, but they carry risks and are generally reserved for patients with more severe disease.
Genetic variations are thought to play a role in scleroderma risk, but so far, this information has not directly translated into new targeted treatments.
A team of scientists in the U.K. and the U.S. set out to identify existing drugs that could potentially be repurposed as scleroderma treatments. Repurposing therapies with established safety profiles is generally faster and less costly than developing new medicines from scratch.
The researchers first analyzed databases of genetic variants associated with scleroderma. This allowed them to identify 12 genes linked to these variants that also have known drug targets. They then cross-referenced these genes with databases of existing medications to identify drugs that could act on these targets.
“By adopting an integrated approach, the predicted pharmacological effects of targeting implicated gene variants can be modelled to existing, well-characterised, drug therapies. This approach provides an effective mechanism to screen a large number of candidate drug therapies against genetically identified targets,” the researchers wrote, noting that “a major advantage of this approach is that these drug therapies are often at later stages of drug development processes for other indications, and thereby more likely to progress (and with efficiencies to be saved) through clinical trials for other indications.”
Analysis links disease-related genes to existing medications
The analysis ultimately identified 89 existing drugs that could potentially be explored as scleroderma treatments. The researchers noted that none of these drugs is included in current scleroderma guidelines or recommendations. However, they highlighted that one of them, amlitelimab, is being investigated in the CONQUEST Phase 2b study (NCT06195072).
CONQUEST is a placebo-controlled platform trial run by the Scleroderma Research Foundation that aims to evaluate multiple potential scleroderma treatments in parallel. The trial is recruiting adults with interstitial lung disease related to scleroderma at sites across the U.S. The fact that this analysis identified a medicine already in clinical testing provides proof of concept for the approach, the researchers said.
The potential treatments identified could be broadly grouped into three categories. Some modulate the activity of female sex hormones, including selective estrogen receptor modulators and degraders. Others target neurotransmitters, while a third group acts on pathways involved in inflammation and fibrosis. The scientists said these medicines may be candidates for future study, but stressed that they are not immediately ready for repurposing and that factors such as potential unintended side effects were not accounted for in their analysis.
“Our data provide biologic rationale and confirmation of disease effector mechanisms for current routes of clinical investigation. Future efforts could build on this work by elucidating the mechanisms underlying the identified targets, thereby helping to accelerate the typically lengthy and complex process of drug target identification and development,” the scientists concluded.
