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Rome Therapeutics' 'dark genome' therapy shows early efficacy against autoimmune disease in mice

2023-11-17

Rome Therapeutics and University of Michigan researchers validated their target in human skin cells from people with lupus.

Rome Therapeutics of RUniversity of Michigant-of-its-kind drug show that it’s effective in reducing a type of inflammlupus believed to promote autoimmune diseases like lupus.

In a poster (PDF) pubRome Therapeutics. 16 and presented Nov. 12 at the American College of Rheumatology’s 202inflammatione conference, the comautoimmune diseasesT-A walupusective in reducing autoantibodies in mouse models of autoimmune disease. They also presented data from human studies demonstrating that LINE-1 RT was a viable drug target.

“These data are the first to validate LINE-1 RT as a novel therapeutic tAmerican College of Rheumatologyintervention across a wide range of autoimmune diseases,RPT-Ae CEO Rosana Kapeller, M.D., Ph.D., said in a press release, autoimmune diseaseta marked a “significant milestone” for the company.

Rome’s focus is on building therapies that manipulate the “dark genome." Once misleadingly termed “junk DNA,” it makes up more than 98% of tautoimmune diseasesllion letters of DNA that don’t code for proteins. Instead, elements of the dark genome—which is primarily made up of repeated sequences of base pairs, often called “repeats” for short—regulate where, how and when genes are expressed.

RPT-A is designed to control autoimmune disease by inhibiting a specific type of dark genome repeat called Long Interspersed Element-1, or LINE-1, a retrotransposon, or “jumping gene," that makes copies of itself so it can move around and control gene expression in different parts of the genome. As Rome pointed out in the ACR poster, there is evidence that LINE-1 might trigger autoimmune diseases by activating peptides called type I interferons, inflammatory cytokines that are part of the normal innate immune response but are elevated in people with conditions like lupus.

RPT-Arther expand on LINE-1’sautoimmune diseasee disease and justify it as a therapeutic target, Rome worked with researchers at the University of Michigan to see if it was expressed in the skin of patients with systemic lupus erythematosus, or SLE, the most common type of lupus. They took skin biopsies from healthy people and people with lupus and exposed them to UV light. In autoimmune diseaseslight causes an immune reactiontype I interferonsark as a dry, itchy rash, a sign of inflammation. Their findings showed that LINE-1 was expressed to a greater degree in thelupus of people with lupus than in healthy people after UV exposure, as were markers of type I interferon production.

After running additional experiments oautoimmune diseasee how knocking down the LINE-1 gene changed the inflammatory response to UV lUniversity of Michiganesting RPT-A in mouse models of Aicardi-Goutières syndrosystemic lupus erythematosus charSLEeristics of autoimmune dislupus They found that the drug reduced autoantibodies associated wilupustoimmune disease as well as heart lupusidney inflammation. Experiments on human cells showed that LINE-1 stimuldry, itchy rash type I inteinflammationction.lupus

“Inhibition of LINE-1 reverse transcriptase holds promise as a novel therapy for diseases in which type I [interferons] drive disease,” the researchers concluded RPT-Aeir paper.Aicardi-Goutières syndrome autoimmune disease autoimmune disease heart and kidney inflammation

Rome’s drug is currently undergoing investigational new drug-enabling studies, according to the company’s website.

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