The compound SCD-153 accelerates the regrowth of mouse fur in comparison with management experiments utilizing a solvent and 4-methyl itaconate. Credit score: PNAS Nexus 2023, 2 (1), pgac297 DOI: 10.1093/pnasnexus/pgac297
A analysis group, led by Dr. Pavel Majer from IOCB Prague, in collaboration with the laboratories of Barbara Slusher and Louis Garza at Johns Hopkins College, has developed a compound that might doubtlessly deal with the autoimmune dysfunction alopecia areata, which causes hair loss, resulting in the formation of bald patches.
The outcomes of their research, just lately printed within the Journal of Medicinal Chemistry, affirm the efficacy of a collection of prodrugs based mostly on derivatives of itaconic acid, merely known as itaconates. Furthermore, there’s a good likelihood that the substances might be administrable orally within the type of tablets and never simply as an ointment.
Itaconate is a naturally occurring substance with anti-inflammatory results elicited by interacting with the immune system. Nevertheless, itaconate has the weak point that it doesn’t simply penetrate the cells. The staff of Pavel Majer, which has spent a number of years growing a drug for alopecia, has surmounted this impediment by growing prodrugs, compounds that convert into an energetic drug solely inside the physique.
“We have prepared a series of prodrugs, at least two of which appear to be highly effective. Tests on mice have confirmed that the compounds are absorbed well and release the active ingredient in the skin at the right concentration. Our itaconate derivatives could thus represent a completely new method of treating alopecia,” says Pavel Majer, head of the Drug Discovery group at IOCB Prague.
Credit score: IOCB Prague
Alopecia areata is an autoimmune dysfunction wherein the immune system assaults hair follicles, resulting in their irritation and consequently to hair loss and impaired hair progress. The situation impacts about 2% of individuals, principally ladies, and is the second commonest explanation for hair loss, after androgenetic alopecia (sample baldness). Present therapies are predominantly based mostly on corticosteroids, which include various unwanted side effects.
The scientists have proved that the brand new substances may carry important reduction to sufferers with alopecia areata. The present article builds on an earlier research by these teams, printed in 2022 in PNAS Nexus.
The appreciable potential of this discovery has additionally been acknowledged by the pharmaceutical firm SPARC, which has bought a license for the patented expertise using itaconate prodrugs. One of many compounds developed, SCD-153, when utilized as an ointment, relieves irritation, protects hair follicles, and based on earlier assessments on mice, accelerates the expansion of recent hair. It does so by making hair follicles transition from a dormant state to an energetic one.
SPARC has already began recruiting sufferers for a section 1 scientific trial of this promising compound.
Extra info:
Chae Bin Lee et al, Discovery of Orally Accessible Prodrugs of Itaconate and Derivatives, Journal of Medicinal Chemistry (2025). DOI: 10.1021/acs.jmedchem.4c02646
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