Researchers at the Francis Crick Institute, UCL Great Ormond Street Institute for Child Health, and Great Ormond Street Hospital for Children (GOSH) have designed a new genetic therapy that could potentially alleviate debilitating giant moles in congenital melanocytic naevus syndrome (CMN), a rare skin condition. The treatment, if successful, could reduce the risk of affected children and adults developing melanoma, a severe type of cancer.
Published in the Journal of Investigative Dermatology, the researchers silenced a gene called NRAS, which is mutated in the cells of these moles, in both cells in a dish and in mice. NRAS belongs to a group of genes (RAS genes) that, when mutated, can cause moles and predispose to cancer.
Silencing RNA Therapy Triggers Mole Cell Self-Destruction
The team used a genetic therapy called silencing RNA, which was delivered in special particles directly to mole cells, to silence the mutated NRAS gene. They gave injections containing the therapy to mice with CMN, which reduced the silenced NRAS gene after just 48 hours. The therapy was also tested in cells and whole skin sections from children with CMN, and silencing the gene triggered the mole cells to self-destruct.
Veronica Kinsler, the study’s lead researcher, said, “CMN is physically and mentally challenging for children and adults living with this condition and for their families. These results are very exciting, as not only does the genetic therapy trigger self-destruction of the mole cells in the lab, but we have managed to deliver it into the skin in mice. These results suggest that the treatment in future could potentially reverse moles in people, however more testing will be needed before we can give it to patients.”
Collaboration and Funding from Multiple Organizations
This research was funded by the National Institute for Health and Care Research (NIHR), Caring Matters Now Charity and Patient Support Group, LifeArc, and the NIHR Great Ormond Street Hospital Biomedical Research Centre. The researchers have been working closely with the Crick’s Translation team to develop the technology towards patient benefit, including securing translational funds from LifeArc to carry out more research in mice to understand how the treatment works over a longer period.
Jodi Whitehouse, CEO of Caring Matters Now, who helped to fund the research, expressed her excitement about the breakthrough, saying it “brings real hope to the lives of those living with CMN.” Catriona Crombie, Head of Rare Disease at LifeArc, highlighted their commitment to improving the lives of people living with rare diseases by investing in promising research and helping scientists overcome translational research barriers.
The researchers have been working with families affected by CMN, whose stories highlight the daily challenges and hopes for a cure. Hanna, 7, Elijah, 10, and Ada, 3, are among the children whose skin samples have been used in this research, with their families hoping for a treatment that could transform their quality of life and reduce the risk of melanoma.
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