Enpatoran

Treatment of autoimmune diseases like lupus has long relied on steroids to knock down the immune system, but more targeted therapies are currently undergoing clinical trials. To make sure these therapies get to the patients who will benefit, work is needed to identify the specific mutations behind each patient's disease. Researchers now report several dozen mutations associated with oversensitive toll-like receptors -- a major cause of autoimmune disease -- and linked two mutations to patients. Lupus is a lifelong, often painful and occasionally lethal autoimmune disease. Few treatments exist today beyond powerful steroids to knock down a patient's immune system -- a therapy that has its own serious risks. The good news is that new and promising treatments are in clinical trials. But the term lupus belies the fact that the disease has a variety of causes, which means that treatments will have to be highly personalized to guarantee that each patient is given the drug that targets the specific genetic mutation responsible for their variety of lupus. Researchers are just now beginning to link specific genetic mutations to subsets of lupus patients, allowing physicians to target therapies to those who will benefit most. In the latest advance, researchers at the University of California, Berkeley, report in a new paper the discovery of two sets of patients with genetic mutations that are nearly identical to mutations that the researchers had earlier pinpointed in mouse and cell lines as linked to autoimmune disease. These two genetic links are among several dozen mutations that the UC Berkeley team recently discovered and linked to lupus, all in one gene that regulates a prime suspect in a subset of lupus patients -- proteins called toll-like receptors (TLR), which enable immune cells to recognize foreign DNA and RNA. According to study leader Gregory Barton, UC Berkeley professor of molecular and cell biology, identifying these mutations could help doctors deliver a personalized treatment to patients with oversensitive TLRs and, in particular, oversensitive TLR7 receptors. "We basically have a map now," said Barton, who is also an investigator in the Howard Hughes Medical Institute. "It's not like everybody that has lupus has a mutation in the gene that causes overactivation of TLRs and TLR7. But there are drugs coming online that very specifically inhibit TLR7. As we sequence more and more people, it will become easier to identify those patients and put them on those drugs. That's a lot better than the current course of therapy for lupus, which is brutal." "This is exciting because the drug will be orally available and is in clinical trials now," said Victoria Rael, a UC Berkeley graduate student who, with fellow graduate student Julian Yano, is a co-first author of the paper. The results of the genetic screens and details of the patients' mutations were published today (May 23) in the Journal of Experimental Medicine. A problem recognizing 'self' Autoimmune diseases, which range from rheumatoid arthritis and Crohn's disease to scleroderma and numerous thyroid conditions, stem from attacks by the immune system on the body's own cells that destroy normal, healthy tissue. Many studies have linked at least two types of autoimmune disease, lupus and psoriasis, to TLRs, which are part of the innate immune system that initially detects foreign invaders, such as viruses and bacteria, and stimulates a first line of attack. Normally, TLRs are delicately tuned to react only to foreign DNA and RNA, but if that tuning is off, they can react to a body's own nucleic acids and proteins associated with nucleic acids, which look much like those of pathogens. What makes this autoimmune reaction so deadly is that the TLRs also activate the body's second-line defense, the more powerful adaptive immune response, mobilizing T and B cells, macrophages, and other cells. These cells then mount a sustained attack that destroys the body's healthy tissue and causes chronic inflammation. The most common form, systemic lupus erythematosus (SLE), for example, is characterized initially by skin rashes -- in particular, a butterfly-shaped rash on the face -- but later by damage to joints, muscles, organs and skin, causing pain and fatigue. It's most commonly seen in females, often starting during the teen years. Lupus, in general, is two to three times more prevalent among women from many ethnic and racial minority groups than among white women. "We think the way the system works is that if nucleic acids find these receptors, most likely they're going to be from a virus," Barton said. "But in some people, the receptor is more responsive, so now levels of self-nucleic acids that otherwise wouldn't stimulate the receptor in a normal person activate the receptor. We think that one of the ways that these mutations are working is that they're making levels of self-nucleic acids that normally wouldn't be stimulatory, stimulatory." Barton and his lab colleagues have been investigating the role of TLRs that are misregulated in lupus, and in particular, one of the main proteins that regulates them: UNC93B1, or UNC for short. Several years ago, a team of postdoctoral fellows and graduate students in his lab screened in cell culture more than 100 genetic mutations in the UNC gene to see which ones overstimulated TLRs and would be good targets for further study. While they published some details in earlier papers, they didn't publish the complete list because there seemed to be little point -- almost no data was available on the genome sequences of lupus patients to compare with the mutations that overstimulated TLRs. But that has changed in recent years, thanks to a plunge in the cost of genome sequencing. That's how the mother of a young girl with severe autoimmune disease found Barton. Her daughter's DNA had been sequenced and showed a mutation in a region of UNC that Barton's team had noted in an earlier paper. Lupus in the family Rael and undergraduate Madeleine Weiss used the same cell culture screening technique to test the novel mutation from the young girl and found that it had an overstimulating effect, similar to the effect of other mutations in that area of the UNC gene. Surprisingly, the patient had the genetic mutation on only one of the two UNC alleles, meaning that she had one normal UNC gene, yet she still suffered severe autoimmune symptoms. Barton and his team also connected with a family of five afflicted with lupus. All had mutations on one UNC allele in another area of the UNC protein that Barton's team had previously identified. That mutation, when screened in cell lines, also produced overactive TLRs. "We were skeptical that just one copy of a gene would be sufficient to cause a disease," Rael said. "It wasn't until we put the patients' mutations into cell lines and saw that they led to very convincing TLR hyper-responsiveness that we realized they had the possibility of being sufficient to be disease-causing." Rael and Yano then repeated the screening work previously performed in the lab and confirmed that 32 distinct mutations in the UNC gene -- about one-third of the mutations tested -- increased the sensitivity of TLR7 to nucleic acids at least twofold. About another five mutants increased TLR7 sensitivity but to a lesser degree. Before these screens, only two mutations in the UNC protein had been linked to increased sensitivity of TLR7 in mice, though three additional human mutations were reported within the last two months. Barton is hopeful that by publishing the complete list of TLR hypersensitivity mutations, doctors can identify other lupus patients who could benefit from the anti-TLR drugs now in clinical trials. One drug, M5049, or Enpatoran, appears to work by latching onto two human receptors, TLR7 and TLR8, and preventing them from binding nucleic acids. Rael, Yano and other members of Barton's lab are investigating further how these unique UNC mutations affect the way a patient manifests the disease. They have recreated these patients' mutations in mice so that they can model human lupus. "With mouse models, you can start thinking about how, even though the mutations are in the same protein, the different mechanisms of TLR regulation break down, which immune cells get activated as a result, and how this can lead to differences in the symptoms patients suffer from," Rael said. The lab also is trying to understand how UNC tunes TLRs, which may be by regulating the number and arrangement of TLRs on immune cells. More TLRs may make a person more sensitive to the small number of self-nucleic acids circulating in the body. "UNC93B1 is important for getting the receptors to the place where they can function, but it also is important for regulating them when they get there," Barton said. "The protein is a very baroque way of trying to make decisions about whether the nucleic acid that you just bound to a TLR is from a virus or from one of your own cells." He hopes that physicians add this gene to the list of lupus-associated genes, "so if they see a mutation like these, even a heterozygous mutation, they will investigate further." Other senior authors of the paper are Bo Liu of the Chinese Academy of Sciences in Shanghai and Olivia Majer of the Max Planck Institute for Infection Biology in Berlin, Germany. The co-authors also include physicians from UC San Francisco, Stanford University, and hospitals in Missouri, North Carolina and Washington. The work was funded in part by the Lupus Research Institute, the Lupus Research Alliance and the National Institutes of Health (R01AI072429).

The inflammatory myositis market is anticipated to surge owing to improvements in diagnosis over the globe and thus the surge in treatment options. In addition, the expected launch of emerging therapies by leading companies such as CSL Behring, Immunoforge Co. Ltd., Argenx, Janssen, Abcuro, Inc., and others will also propel the inflammatory myositis market size. LAS VEGAS, July 18, 2023 /PRNewswire/ -- DelveInsight's Inflammatory Myositis Market Insights report includes a comprehensive understanding of current treatment practices, inflammatory myositis emerging drugs, market share of individual therapies, and current and forecasted market size from 2019 to 2032, segmented into 7MM [the United States, the EU-4 (Italy, Spain, France, and Germany), the United Kingdom, and Japan]. Key Takeaways from the Inflammatory Myositis Market Report As per DelveInsight analysis, the inflammatory myositis market size in the 7MM was approximately USD 575 million in 2022. According to the assessment done by DelveInsight, the estimated total diagnosed prevalent inflammatory myositis cases in the 7MM were approximately 184K in 2022. Leading inflammatory myositis companies such as CSL Behring, Immunoforge Co. Ltd., Argenx, Janssen, Abcuro, Inc., Horizon Therapeutics, Merck KGaA, Galapagos NV, Priovant Therapeutics, Roivant, Alexion Pharmaceuticals, Pfizer, Kezar Life Sciences, and others are developing novel inflammatory myositis drugs that can be available in the inflammatory myositis market in the coming years. The promising inflammatory myositis therapies in the pipeline include Hizentra, PF 1801, Efgartigimod, Nipocalimab, ABC008, Daxdilimab (HZN-7734/MEDI7734/VIB7734), Enpatoran (M5049), GLPG3667, Brepocitinib (PF-06700841), ULTOMIRIS (Ravulizumab), PF-06823859 (Dazukibart), Zetomipzomib (KZR-616), and others. Discover which therapies are expected to grab the major inflammatory myositis market share @ Inflammatory Myositis Market Report Inflammatory Myositis Overview Inflammatory myositis, often known as myositis, is a rare autoimmune condition characterized by muscular inflammation. Polymyositis, dermatomyositis, inclusion body myositis, and necrotizing autoimmune myopathy are all examples of inflammatory myositis. The exact cause of inflammatory myositis is unknown, although it is thought to be related to an aberrant immunological response in which the body's immune system destroys its own muscle tissue by mistake. Muscle weakness, muscle soreness, difficulty swallowing, weariness, and, in certain cases, skin rashes are the most common symptoms of inflammatory myositis. The severity of the inflammatory myositis symptoms varies and may worsen over time. Dermatomyositis is characterized by skin rashes, which frequently include the face and upper torso. A medical history, physical examination, blood tests, electromyography (EMG), muscle biopsy, and imaging techniques such as MRI are commonly used to identify inflammatory myositis. Inflammatory Myositis Epidemiology Segmentation DelveInsight estimates that there were approximately 184K diagnosed prevalent cases of inflammatory myositis in the 7MM in 2022. According to DelveInsight estimates, assessments indicate that within the age groups of 0–17 years, 18–44 years, 45–64 years, and 65 years and above, a greater prevalence of diagnosed cases of inflammatory myositis was observed among individuals aged 45–64 years with 77.6K cases in 2022 in the 7MM. The inflammatory myositis market report proffers epidemiological analysis for the study period 2019–2032 in the 7MM segmented into: Total Inflammatory Myositis Diagnosed Prevalent Cases Inflammatory Myositis Type-specific Cases Inflammatory Myositis Age-specific Diagnosed Prevalent Cases Inflammatory Myositis Gender-specific Diagnosed Prevalent Cases Inflammatory Myositis Treatment Market Inflammatory myositis is usually treated with a mix of pharmaceutical treatments and supportive measures. The primary goals of inflammatory myositis treatment are to reduce inflammation, manage symptoms, preserve muscle function, and avoid potential consequences. Currently, therapeutic techniques for inflammatory myositis include a combination of immunosuppressive medications such as corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs) such as immunosuppressive agents. Biologic drugs, physical therapy, and supportive measures are also used. Biologic drugs such as rituximab or tocilizumab, which precisely targets immune system components to decrease inflammation, may be used in patients with severe or resistant inflammatory myositis.In more severe or resistant cases, drugs such as cyclophosphamide or cyclosporine may be administered to dampen the immune response and reduce inflammation. If corticosteroids, immunosuppressive drugs, and IVIG fail to relieve symptoms, IV cyclophosphamide can be used as a last-resort treatment. Prograf capsules (generic name: tacrolimus) are an immunosuppressive medicine extensively used in the treatment of a variety of medical diseases, including myositis, in Japan. The US Food and Drug Administration (FDA) has approved OCTAGAM 10% (Immune Globulin Intravenous [Human]) for the treatment of adult dermatomyositis, a rare immune-mediated inflammatory disease. The US FDA has approved ACTHAR Gel (repository corticotropin injection) for use in individuals with two subtypes of idiopathic inflammatory myopathies (IIMs), dermatomyositis (DM) and polymyositis (PM). ACTHARGel is a naturally occurring blend of adrenocorticotropic hormone analogues and pituitary peptides. To know more about inflammatory myositis treatment, visit @ Inflammatory Myositis Treatment Drugs Key Inflammatory Myositis Therapies and Companies Hizentra: CSL Behring PF 1801: Immunoforge Co. Ltd. Efgartigimod: Argenx Nipocalimab: Janssen ABC008: Abcuro, Inc. Daxdilimab (HZN-7734/MEDI7734/VIB7734): Horizon Therapeutics Enpatoran (M5049): Merck KGaA GLPG3667: Galapagos NV Brepocitinib (PF-06700841): Priovant Therapeutics/Roivant ULTOMIRIS (Ravulizumab): Alexion Pharmaceuticals PF-06823859 (Dazukibart): Pfizer Zetomipzomib (KZR-616): Kezar Life Sciences Learn more about the FDA-approved drugs for inflammatory myositis @ Drugs for Inflammatory Myositis Treatment Inflammatory Myositis Market Dynamics The inflammatory myositis market is expected to change in the coming years. The therapeutic landscape is abundant in terms of assessing the efficacy, safety, and tolerability of innovative medications in patients with inflammatory myositis and its different forms. Rising data on the general prevalence of inflammatory myositis and its subtypes is predicted to dramatically increase the patient pool. Moreover, the inflammatory myositis companies and academics are working to assess challenges and seek opportunities that could influence inflammatory myositis R&D. The therapies under development are focused on novel approaches to treat/improve the disease condition. Inflammatory myositis companies are involved in developing inflammatory myositis therapies. Moreover, the anticipated introduction of emerging therapies with improved efficacy and a further improvement in the diagnosis rate are expected to drive the growth of the inflammatory myositis market in the 7MM. However, certain factors may affect the growth of the inflammatory myositis market. The growing pipeline is gloomy, with a scarcity of effective late-stage drugs. The existing therapeutic options are linked with concerning side effects such as renal toxicity, nausea, osteoporosis, pulmonary toxicity, and others. Moreover, the inflammatory myositis market growth may be offset by unaffordable pricing, market access and reimbursement issues, and a shortage of healthcare specialists. In addition, the undiagnosed, unreported cases and the unawareness about the disease may also impact the inflammatory myositis market growth. Scope of the Inflammatory Myositis Market Report Therapeutic Assessment: Inflammatory Myositis current marketed and emerging therapies Inflammatory Myositis Market Dynamics: Attribute Analysis of Emerging Inflammatory Myositis Drugs Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's Views, Analyst's Views, Inflammatory Myositis Market Access and Reimbursement Discover more about inflammatory myositis drugs in development @ Inflammatory Myositis Clinical Trials Table of Contents Related Reports Myositis Pipeline Myositis Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key myositis companies, including GlaxoSmithKline, Corbus Pharmaceuticals, Abcuro, Inc., Orphazyme, Bristol-Myers Squibb, Kezar Life Sciences, Inc., Horizon Therapeutics, Viela Bio, Paean Biotechnology Inc., Alexion Pharmaceuticals, Janssen Biotech, CSL Behring, Pfizer, Roche, among others. Inclusion Body Myositis Epidemiology Forecast Inclusion Body Myositis Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted inclusion body myositis epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Inclusion Body Myositis Market Inclusion Body Myositis Market Insight, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the market trends, market drivers, market barriers, and key inclusion body myositis companies, including Acceleron Pharma Inc, KPI Therapeutics Inc, Milo Biotechnology LLC, Nobelpharma Co Ltd, Orphazyme ApS, Ultragenyx Pharmaceutical Inc, among others. Inclusion Body Myositis Pipeline Inclusion Body Myositis Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key inclusion body myositis companies, including Acceleron Pharma Inc, KPI Therapeutics Inc, Milo Biotechnology LLC, Nobelpharma Co Ltd, Orphazyme ApS, Ultragenyx Pharmaceutical Inc, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP