MSGID: 1:317/3 6279ea91   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Drugs showing promise in cancer trials reduce scarring for scleroderma   
    The findings could lead to repurposing drugs for patients with the   
   sometimes-fatal condition    
      
     Date:   
         May 9, 2022   
     Source:   
         Michigan Medicine - University of Michigan   
     Summary:   
         Epigenetic drugs that have shown promise in cancer trials   
         significantly reduce scarring in the cells of patients with   
         scleroderma, a new study shows. Results reveal that drugs that   
         inhibit BRD4, known to play a role in cancer, also affect fibrosis   
         in scleroderma. Researchers tested BRD4 inhibitors on the skin   
         fibroblasts of scleroderma patients and in mouse models of skin   
         fibrosis, finding that the treatment stopped scarring in both   
         human-derived cells and in animals.   
      
      
      
   FULL STORY   
   ==========================================================================   
   Epigenetic drugs that have shown promise in cancer trials significantly   
   reduce scarring in the cells of patients with scleroderma, an incurable   
   and life- threatening autoimmune disease, a new study shows.   
      
      
   ==========================================================================   
   Scleroderma is a chronic disease that affects the immune system, causing   
   a buildup of scar-like tissues in the skin and internal organs known   
   as fibrosis.   
      
   This process occurs when cells that make up connective tissue, called   
   fibroblasts, produce too much collagen that causes the skin and organs   
   of patients to harden -- resulting in tissue damage and organ failure.   
      
   In a recent study, Michigan Medicine researchers focused on BETs,   
   which are proteins that regulate gene expression by binding to   
   modifications on proteins around which DNA wraps, a process called   
   epigenetic regulation. Drugs targeting BETs, specifically an isoform   
   called BRD4, have been developed by various pharmaceutical companies   
   for cancer treatment.   
      
   Results published in JCI Insight reveal that drugs that inhibit   
   BRD4, known to play a role in cancer, also affect fibrosis in   
   scleroderma. Researchers tested BRD4 inhibitors on the skin fibroblasts of   
   scleroderma patients and in mouse models of skin fibrosis. They found that   
   the treatment stopped scarring in both human-derived cells and in animals.   
      
   The inhibitors used by Michigan Medicine researchers have shown promise   
   for treating various cancers in preclinical studies. Specifically,   
   one drug used in the recent study, called AZD5153, is being tested in   
   a Phase I clinical trial for sarcomas and lymphomas.   
      
   "Through this study, we have uncovered a new class of epigenetic drugs   
   that can be used in scleroderma fibrosis," said Pen-Suen Tsou (Eliza),   
   Ph.D., senior author of the paper and a rheumatology researcher at   
   Michigan Medicine. "If we can repurpose these drugs and get them through   
   development more quickly, we can provide faster relief for patients who   
   struggle with debilitating symptoms of this autoimmune disease. The   
   process can typically take around 10 years, but our patients cannot   
   wait that long."  The study is a collaborative effort with Michigan   
   Medicine's Scleroderma Program. Tsou's team also found that a calcium   
   signaling protein, called CaMKII, affects fibrosis in scleroderma,   
   which researchers had previously not seen.   
      
   "Right now, we are doing some follow up studies to see if inhibitors   
   of this protein can block scarring for scleroderma," Tsou said. "This   
   opens up a brand- new direction for us to offer a novel target for   
   this disease."  Additional authors include: Sirapa Vichaikul, B.S.,   
   Mikel Gurrea-Rubio, Ph.D., M. Asif Amin, M.D., Phillip L. Campbell,   
   B.S., Qi Wu, Ph.D., Megan N.   
      
   Mattichak, William D. Brodie, Pamela J. Palisoc, B.S., Mustafa Ali, B.S.,   
   Sei Muraoka, M.D., Ph.D., Jeffrey H. Ruth, Ph.D., Ellen N. Model, B.S.,   
   Dallas M.   
      
   Rohraff, B.S., M.P.H., Jonatan L. Hervoso, B.S., Yang Mao-Draayer, M.D.,   
   Ph.D., David A. Fox, M.D., Dinesh Khanna, M.B.B.S., M.Sc., all of Michigan   
   Medicine, and Amr H. Sawalha, M.D., University of Pittsburgh.   
      
      
   ==========================================================================   
   Story Source: Materials provided by   
   Michigan_Medicine_-_University_of_Michigan. Original written by Noah   
   Fromson. Note: Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Sirapa Vichaikul, Mikel Gurrea-Rubio, M. Asif Amin, Phillip   
      L. Campbell,   
         Qi Wu, Megan N. Mattichak, William D. Brodie, Pamela J. Palisoc,   
         Mustafa Ali, Sei Muraoka, Jeffrey H. Ruth, Ellen N. Model, Dallas   
         M. Rohraff, Jonatan L. Hervoso, Yang Mao-Draayer, David A. Fox,   
         Dinesh Khanna, Amr H.   
      
         Sawalha, Pei-Suen Tsou. Inhibition of bromodomain extraterminal   
         histone readers alleviates skin fibrosis in experimental models   
         of scleroderma.   
      
         JCI Insight, 2022; 7 (9) DOI: 10.1172/jci.insight.150871   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2022/05/220509162807.htm   
      
   --- up 10 weeks, 10 hours, 50 minutes   
    * Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)   
   SEEN-BY: 15/0 106/201 114/705 123/120 129/330 331 153/7715 218/700   
   SEEN-BY: 229/110 111 112 317 400 426 428 470 664 700 292/854 298/25   
   SEEN-BY: 305/3 317/3 320/219 396/45   
   PATH: 317/3 229/426