Researchers say they have discovered a promising target for new drugs that might be able to reverse the fibrosis process in systemic sclerosis or scleroderma – a rare disease that cuts short the lives of many patients and for which there is no cure or effective treatment.
Richard Neubig, professor and chairperson of the Department of Pharmacology and Toxicology at Michigan State University, and colleagues found a core genetic signaling pathway that activates scleroderma and showed can be switched off in mice with the help of a small molecule.
They report their study in the Journal of Pharmacology and Experimental Therapeutics.
Scleroderma is a rare autoimmune disease that happens when the immune system makes too much scar tissue – as if in an attempt to repair damage to tissue – causing it to thicken with too much collagen (a process known as fibrosis).
There are two types of scleroderma – localized and systemic sclerosis. In localized scleroderma the fibrosis often happens in the skin, which gets thicker and progressively less flexible. Systemic sclerosis occurs with variable degree of skin fibrosis, but it spreads to other organs too, causing hardening of tissue in the lungs, kidneys, gut and heart.
Estimates suggest around 300,000 Americans have scleroderma, of whom a third have the systemic form.
Like many complex autoimmune disorders that start in adulthood, animal models replicate some, but not all the characteristics of the disease, which makes it difficult to study and accounts for the slowness of progress in this field.
The most that patients can expect from current treatments is a reduction in inflammation – there is no effective treatment or cure.
But this new study could be about to change all that, as Prof. Neubig, who co-led the research, explains:
“This research shows that by inhibiting this main signaling pathway, we can block fibrosis – the thickening of tissue that occurs with the disease.”
Drugs that block one or two signaling pathways known to cause the disease do exist – but scleroderma can be triggered by any one of many pathways, say the researchers.
The difference that this study makes is that the researchers believe they have identified the core signaling pathway that throws the main switch for all the signaling pathways.
The core signaling pathway is called the MRTF/SRF gene transcription pathway, and the researchers carried out experiments in culture and mice to show a new small-molecule inhibitor of this pathway can flip this main switch and reverse the fibrosis process.
Now they need to translate this success in the lab to show it works in humans.
“By validating this core switch as a viable drug target, we can now continue our work to improve the chemical compounds so they will work with doses that are appropriate for people. It’s definitely promising,” says Prof. Neubig.
He adds that the finding could significantly change the quality of life for scleroderma patients and greatly lengthen the lives of systemic patients.
Funds for the study came from a Michigan family – Jon and Lisa Rye – who have firsthand experience of scleroderma and its effects. Additional funds came from the Scleroderma Cure Fund, a crowd funding site set up by the family.
In October 2013, Medical News Today learned of another exciting development in this field, where researchers prevented and reversed fibrosis in mice with stiff skin syndrome.