Upcoming treatments for morphea.
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ABSTRACT:
SUBMITTER: Wenzel D
PROVIDER: S-EPMC8589364 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Purpose of reviewTo highlight new and emerging treatment targets in myositis.Recent findingsThe landscape of novel therapeutics in myositis has vastly changed in the past 5 years. This is largely due to a greater understanding of the pathogenesis of myositis and validation of more robust outcome measures that standardize the ability to assess treatment response. Clinical trials in dermatomyositis are leading the way with ongoing multicenter, international phase 3 clinical trials. Proof-of-concept studies targeting the JAK/STAT pathway have also showed early promise in treating refractory dermatomyositis in adults and children. This review highlights that the future armamentarium of therapeutic drugs will likely be larger and more selective in treating different subgroups of myositis.
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Project description:Narcolepsy is a chronic, disabling neurologic disorder characterised by excessive daytime sleepiness (EDS) and, in up to 60% of patients, cataplexy. Treatments for narcolepsy are aimed at improving wakefulness (e.g. modafinil, armodafinil, stimulants), reducing cataplexy attacks (e.g. sodium oxybate, venlafaxine), and treating the symptoms of disturbed nocturnal sleep, sleep paralysis and sleep-related hallucinations (e.g. sodium oxybate). In general, medications that increase the release, or inhibit the reuptake, of norepinephrine or dopamine have wake-promoting effects and are useful in managing EDS, whereas medications that inhibit serotonin or norepinephrine reuptake have anticataplectic effects. Modulation of γ-aminobutyric acid B (GABAB) receptors or histamine H3 receptors (H3Rs) has effects on both EDS and cataplexy. Pitolisant, an H3R antagonist, and solriamfetol, a dopamine and norepinephrine reuptake inhibitor, are the most recently approved treatments for EDS associated with narcolepsy in the European Union (pitolisant) and the USA (pitolisant and solriamfetol). Several new agents are being developed and tested as potential treatments for EDS and cataplexy associated with narcolepsy; these agents include novel oxybate formulations (once-nightly [FT218]; low sodium [JZP-258]), a selective norepinephrine reuptake inhibitor (AXS-12), and a product combining modafinil and an astroglial connexin inhibitor (THN102). This review summarises the mechanisms of action, pharmacokinetics, efficacy, and safety/tolerability of recently approved and emerging treatments for narcolepsy.
| S-EPMC6982634 | biostudies-literature
Project description:Pre-exposure prophylaxis (PrEP) against HIV infection with tenofovir/emtricitabine is proven to be effective yet uptake of this preventive measure has been difficult due to several barriers such as cost, access, and misinformation. Certain subpopulations are disproportionately affected by this problem. Several methods have been developed to close the gap in care. New antiretroviral treatment strategies are being investigated for safety and efficacy in preventing HIV infection.
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Project description:BackgroundThe most advanced disease-modifying therapies (DMTs) in development for Huntington's disease (HD) require intrathecal (IT) administration, which may create or exacerbate bottlenecks in resource capacity.ObjectiveTo understand the readiness of healthcare systems for intrathecally administered HD DMTs in terms of resource capacity dynamics and implications for patients' access to treatment.MethodsForty HD centres across 12 countries were included. Qualitative and quantitative data on current capacity in HD centres and anticipated capacity needs following availability of a DMT were gathered via interviews with healthcare professionals (HCPs). Data modelling was used to estimate the current capacity gap in HD centres.ResultsFrom interviews with 218 HCPs, 25% of HD centres are estimated to have the three components required for IT administration (proceduralists, nurses and facilities). On average, 114 patients per centre per year are anticipated to receive intrathecally administered DMTs in the future. At current capacity, six of the sampled centres are estimated to be able to deliver DMTs to all the anticipated patients based on current resources. The estimated waiting time for IT administration at current capacity will average 60 months (5 years) by the second year after DMT availability.ConclusionAdditional resources are needed in HD centres for future DMTs to be accessible to all anticipated patients. Timely collaboration by the HD community will be needed to address capacity gaps. Healthcare policymakers and payers will need to address costs and navigate challenges arising from country- or region-specific healthcare delivery schemes.
| S-EPMC8293639 | biostudies-literature
Project description:Morphea, also known as localized scleroderma, is a chronic inflammatory connective tissue disorder with variable clinical presentations, that affects both adults and children. It is characterized by inflammation and fibrosis of the skin and underlying soft tissue, in certain cases even of the surrounding structures such as fascia, muscle, bone and central nervous system. While the etiology is still unknown, many factors may contribute to disease development, including genetic predisposition, vascular dysregulation, TH1/TH2 imbalance with chemokines and cytokines associated with interferon-γ and profibrotic pathways as well as certain environmental factors. Since the disease may progress to permanent cosmetic and functional sequelae, it is crucial to properly assess the disease activity and to initiate promptly the adequate treatment, thus preventing subsequent damage. The mainstay of treatment is based on corticosteroids and methotrexate. These, however, are limited by their toxicity, especially if applied long-term. Furthermore, corticosteroids and methotrexate often do not sufficiently control the disease and/or the frequent relapses of morphea. This review presents the current understanding of morphea by discussing its epidemiology, diagnosis, management and prognosis. In addition, it will describe recent pathogenetic findings, thus proposing potential novel targets for therapeutic development in morphea.
| S-EPMC9969991 | biostudies-literature
Project description:Skin autoimmune conditions belong to a larger group of connective tissue diseases and primarily affect the skin, but might also involve underlying tissues, such as fat tissue, muscle, and bone. Autoimmune antibodies (autoantibodies) play a role in autoimmune skin diseases, such as localized scleroderma also termed morphea, and systemic scleroderma, also called systemic sclerosis (SSc). The detailed studies on the biological role of autoantibodies in autoimmune skin diseases are limited. This results in a few available tools for effective diagnosis and management of autoimmune skin diseases. This review aims to provide an update on the detection and most recent research on autoantibodies in morphea. Several recent studies have indicated the association of autoantibody profiles with disease subtypes, damage extent, and relapse potential, opening up exciting new possibilities for personalized disease management. We discuss the role of existing autoantibody tests in morphea management and the most recent studies on morphea pathogenesis. We also provide an update on novel autoantibody biomarkers for the diagnosis and study of morphea.
| S-EPMC6634257 | biostudies-literature
Project description:Morphea, also known as localized scleroderma, encompasses a group of idiopathic sclerotic skin diseases. The spectrum ranges from relatively mild phenotypes, which generally cause few problems besides local discomfort and visible disfigurement, to subtypes with severe complications such as joint contractures and limb length discrepancies. Eosinophilic fasciitis (EF, Shulman syndrome) is often regarded as belonging to the severe end of the morphea spectrum. The exact driving mechanisms behind morphea and EF pathogenesis remain to be elucidated. However, extensive extracellular matrix formation and autoimmune dysfunction are thought to be key pathogenic processes. Likewise, these processes are considered essential in systemic sclerosis (SSc) pathogenesis. In addition, similarities in clinical presentation between morphea and SSc have led to many theories about their relatedness. Importantly, morphea may be differentiated from SSc based on absence of sclerodactyly, Raynaud's phenomenon, and nailfold capillary changes. The diagnosis of morphea is often based on characteristic clinical findings. Histopathological evaluation of skin biopsies and laboratory tests are not necessary in the majority of morphea cases. However, full-thickness skin biopsies, containing fascia and muscle tissue, are required for the diagnosis of EF. Monitoring of disease activity and damage, especially of subcutaneous involvement, is one of the most challenging aspects of morphea care. Therefore, data harmonization is crucial for optimizing standard care and for comparability of study results. Recently, the localized scleroderma cutaneous assessment tool (LoSCAT) has been developed and validated for morphea. The LoSCAT is currently the most widely reported outcome measure for morphea. Care providers should take disease subtype, degree of activity, depth of involvement, and quality-of-life impairments into account when initiating treatment. In most patients with circumscribed superficial subtypes, treatment with topical therapies suffices. In more widespread disease, UVA1 phototherapy or systemic treatment with methotrexate (MTX), with or without a systemic corticosteroid combination, should be initiated. Disappointingly, few alternatives for MTX have been described and additional research is still needed to optimize treatment for these debilitating conditions. In this review, we present a state-of-the-art flow chart that guides care providers in the treatment of morphea and EF.
| S-EPMC5506513 | biostudies-literature
Project description:INTRODUCTION:Morphea (localized scleroderma) is a rare cutaneous disease characterized by skin fibrosis of unknown pathogenesis. Transforming growth factor-? (TGF-?) is a potent profibrotic factor. The role of TGF-? in morphea remains unclear. AIM:The goal of this study was to estimate the expression level of TGF-?1 in skin and peripheral blood mononuclear cells as well as the plasma levels of TGF-?1 in plaque morphea (MEP). MATERIAL AND METHODS:The study involved 20 MEP patients. Three control groups were involved: 1 - plasma: 36 healthy volunteers; 2 - PBMC: 47 healthy volunteers; 3 - skin biopsies: 13 samples collected during mastectomy (breast cancer was not skin involved). The analysis of TGF-?1 plasma levels was performed with the use an adequate ELISA kit, while real-time polymerase chain reaction was employed for the expression of TGF-?1 in peripheral blood mononuclear cells (PBMC) and skin. RESULTS:In our study we have not detected differences in TGF-? 1 expression in PBMC, skin, nor in plasma levels of TGF-?1 between MEP patients and healthy controls, regardless of disease activity and its duration. CONCLUSIONS:The results of our study contradict the claim of the substantial role of TGF-?1 in the most common morphea subtype - MEP.
| S-EPMC3907897 | biostudies-literature
Project description:INTRODUCTION:Morphea is a disease included in the group of scleroderma type autoimmune diseases. Interleukin (IL)-17A may play a role at every stage of its pathogenesis. The study aimed at evaluation of IL-17A and IL-23 (as the main cytokine which is supposed to stimulate and maintain synthesis of IL-17) in pathogenesis of morphea. MATERIAL AND METHODS:The studies were performed on 41 blood samples from patients with morphea. Skin was sampled from 29 patients. The evaluation included: (1) expression of IL-17A and IL-23 genes in peripheral blood mononuclear cells (PBMC) using real-time polymerase chain reaction (PCR), (2) plasma concentrations of IL-17A and IL-23 using ELISA, (3) expression of IL-17A and IL-23 genes in skin using real-time PCR. RESULTS:The results of gene expression are expressed as median number of copies per million copies of GAPDH. Higher expression of IL-17A has been demonstrated in PBMC of morphea vs. control group (2630 and 1906 respectively; p = 0.004), accompanied by absence of significant differences in its plasma concentration (10 pg/ml in both groups) and by lowered expression in affected skin (9119 and 19113 respectively; p = 0.036). The results failed to demonstrate elevated IL-23 plasma concentration in morphea vs. control group (5 pg/ml and 6 pg/ml respectively; p = 0.335) or its increased expression in the skin (292 vs. 427; p = 0.383), although we noted its increased expression in PBMC (4419 vs. 808; p < 0.001). CONCLUSIONS:BASED ON THE OBSERVED CORRELATIONS WE SUGGEST THAT: (1) IL-17A does not represent a factor which promotes tissue injury in morphea, (2) IL-23 may playa role in pathogenesis of morphea.
| S-EPMC3542501 | biostudies-literature
Project description:Fibroblast were isolated from either back or forearm punch biopsies taken by Dr. Kari Connolly(UCSF) from either normal control patients, patients with a diagnosis of Systemic Sclerosis with Diffuse Scleroderma and patients with a diagnosis of morphea. Scleroderma fibroblast were grown to confluence, media was changed and the RNA prepared from the cells 48 hrs later (to avoid serum responsive genes). A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Keywords: disease_state_design
2005-12-21 | GSE3886 | GEO