Cystic Fibrosis: The Dawn of a New Therapeutic Era.
Ontology highlight
ABSTRACT:
SUBMITTER: Heltshe SL
PROVIDER: S-EPMC5422649 | biostudies-literature | 2017 Apr
REPOSITORIES: biostudies-literature
Publications
Cystic Fibrosis: The Dawn of a New Therapeutic Era.
Heltshe Sonya L SL Cogen Jonathan J Ramos Kathleen J KJ Goss Christopher H CH
American journal of respiratory and critical care medicine 20170401 8
Similar Datasets
Project description:Cystic fibrosis is the most prevalent inherited disease caused by a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The impaired electrolyte homeostasis caused by the mutated or absent protein leads to symptoms in multiple organ systems. However, the pulmonary manifestation with chronic infections and eventually respiratory failure remains the most important threat. Until one decade ago, only symptomatic treatment was available. However, since 2012, different combinations of CFTR modulators are available for people with cystic fibrosis (pwCF) that carry different mutations. The advent of these drugs has impressively changed life expectancy and quality of life in people with cystic fibrosis and raised new challenges regarding long-term complications and tapering of conventional therapies.Conclusion: In this review, we provide an update on the latest developments around diagnostics, treatment, and prognosis of pwCF. What is Known: • Cystic fibrosis is an incurable and life-shortening disease asking for life-long symptomatic treatment. • Three combination CFTR modulating drugs has gained marked approval over the last 10 years. What is New: • The emerge of new (modulating) therapies contribute to the increasing life expectancy. • A high unmet need to develop new therapies for people with CF who cannot access or benefit from these drugs remains. This review gives an update on the current status.
| S-EPMC8346380 | biostudies-literature
Project description: Not available
| S-EPMC5873629 | biostudies-literature
Project description:BackgroundCardiovascular disease (CVD) risks are increasing in people with cystic fibrosis (pwCF). While cholesterol levels were historically low in pwCF, higher levels after initiating highly effective modulator therapy (HEMT) have been reported. Mechanisms are unclear and there is little guidance on screening.ObjectivesTo evaluate serum lipid changes at multiple timepoints after ivacaftor initiation, and to assess current screening practices for CVD risk factors among CF providers.DesignThis was a post-hoc correlative analysis of prospectively collected clinical data and serum samples from the GOAL cohort study. Cross-sectional survey methodology was also employed.MethodsWe evaluated serum lipids (total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)) at baseline, 3- and 18 months after ivacaftor initiation using samples from the GOAL study biorepository. We also surveyed CF providers across the United States on their CVD risk screening practices.ResultsFifty GOAL participants' samples were analyzed. Using the repeated measures model, TC significantly varied by visit (p = 0.004), driven by a significant increase from baseline at 3 months (mean difference 9.4 mg/dL). This difference diminished by 18 months. BMI was a significant covariate for TC. No significant differences by visit were detected in LDL or HDL. Seventy-five respondents participated in the survey (response rate 5.6%; 41 adult providers, 18 pediatric providers, and 10 providers caring for both) with 67% reporting no lipid screening policy existed in their center. In the past year, 29% of adult providers prescribed lipid-lowering therapy, 54% started anti-hypertensive medications, and 48% initiated ischemic cardiac evaluations for pwCF.ConclusionTC significantly increased within 3 months of initiating ivacaftor, but subsequently diminished toward baseline by 18 months. Lipid screening practices among CF providers were variable and providers are increasingly being confronted with managing CVD risk factors. Partnering with primary care providers is likely to become increasingly important in CF care models.
| S-EPMC11786282 | biostudies-literature
Project description:Wake-up stroke or stroke with unclear onset of symptoms is known to occur in one-fourth of ischemic stroke patients. These patients are not considered for thrombolytic therapy based on time designation of their symptom onset as per the current guidelines. Observational studies have investigated the pathophysiology and suggested actual onset of symptoms to be approximate to the awakening time for these patients. Use of advanced imaging modalities in these patients tends to identify favorable patient profiles for thrombolysis. Results of the ongoing trials will likely beckon a seminal juncture in stroke therapy and deliver critical modifications in the current treatment guidelines for thrombolysis in this substantial, yet neglected, group of stroke patients. In this article, we have reviewed the predisposing factors, preferred imaging modalities and various ongoing thrombolytic and endovascular trials to date for patients with unclear time of symptom onset or who wake up with stroke symptoms.
| S-EPMC6126251 | biostudies-other
Project description:A major advancement has recently occurred in the ability to predict protein secondary structure from sequence using artificial neural networks. This new accessibility to high-quality predicted structures provides a big opportunity for the protein design community. It is particularly welcome for membrane protein design, where the scarcity of solved structures has been a major limitation of the field for decades. Here, we review the work done to date on the membrane protein design and set out established and emerging tools that can be used to most effectively exploit this new access to structures.
| S-EPMC10521746 | biostudies-literature
Project description:During their development and progression tumors acquire numerous mutations that, when translated into proteins give rise to neoantigens that can be recognized by T cells. Initially, neoantigens were not recognized as preferred targets for cancer immunotherapy due to their enormous diversity and the therefore limited options to develop "one fits all" pharmacologic solutions. In recent years, the experience obtained in clinical trials demonstrating a predictive role of neoantigens in checkpoint inhibition has changed our view on the clinical potential of neoantigens in cancer immunotherapy. Technological advances such as sequencing of whole cancer genomes, the development of reliable algorithms for epitope prediction, and an increasing number of immunotherapeutic options now facilitate the development of personalized tumor therapies directly targeting a patient's neoantigenic burden. Preclinical studies in mice that support the excellent therapeutic potential of neoantigen-directed immunotherapies have provided blueprints on how this methodology can be translated into clinical applications in humans. Consistently, very recent clinical studies on personalized vaccinations targeting in silico predicted neoepitopes shed a first light on the therapeutic potential of personalized, neoantigen-directed immunotherapies. In our review, we discuss the various subtypes of tumor antigens with a focus on neoantigens and their potential in cancer immunotherapy. We will describe the current methods and techniques of detection as well as the structural requirements for neoantigens that are needed for their recognition by T cells and for tumor destruction. To assess the clinical potential of neoantigens, we will discuss their occurrence and functional relevance in spontaneous and hereditary cancers and their prognostic and predictive value. We will present in detail the existing immunotherapeutic options that exploit the neoantigen burden of tumors encompassing both preclinical efforts that provided convincing technological proof-of-concept and the current clinical studies confirming the potential of neoantigen-directed immunotherapies.
| S-EPMC5742119 | biostudies-literature
Project description:Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, and the condition is typified by barrier dysfunction and immune dysregulation. Recent studies have characterized various phenotypes and endotypes of AD and elucidated the mechanism. Numerous topical and systemic narrow targeting therapies for AD have been developed according to these findings. Topical medications, including Janus kinase (JAK) inhibitors, phosphodiesterase 4 inhibitors, and the aryl hydrocarbon receptor agonist tapinarof, are effective and safe for AD compared to topical corticosteroids. Oral JAK inhibitors and monoclonal antibodies targeting interleukin (IL)-4, IL-13, IL-31, IL-33, OX40, thymic stromal lymphopoietin, and sphingosine 1-phosphate signaling have displayed outstanding efficacy against moderate-to-severe AD. We are currently in a new era of AD treatment.
| S-EPMC9605067 | biostudies-literature
Project description:2018 was the year of the first marketing authorization of an allogeneic stem cell therapy by the European Medicines Agency. The authorization concerns the use of allogeneic adipose tissue-derived mesenchymal stromal cells (MSCs) for treatment of complex perianal fistulas in Crohn's disease. This is a breakthrough in the field of MSC therapy. The last few years have, furthermore, seen some breakthroughs in the investigations into the mechanisms of action of MSC therapy. Although the therapeutic effects of MSCs have largely been attributed to their secretion of immunomodulatory and regenerative factors, it has now become clear that some of the effects are mediated through host phagocytic cells that clear administered MSCs and in the process adapt an immunoregulatory and regeneration supporting function. The increased interest in therapeutic use of MSCs and the ongoing elucidation of the mechanisms of action of MSCs are promising indicators that 2019 may be the dawn of the therapeutic era of MSCs and that there will be revived interest in research to more efficient, practical, and sustainable MSC-based therapies. Stem Cells Translational Medicine 2019;8:1126-1134.
| S-EPMC6811696 | biostudies-literature
Project description:Following the success of recent endovascular trials, endovascular therapy has emerged as an exciting addition to the arsenal of clinical management of patients with acute ischemic stroke (AIS). In this paper, we present an extensive overview of intravenous and endovascular reperfusion strategies, recent advances in AIS neurointervention, limitations of various treatment paradigms, and provide insights on imaging-guided reperfusion therapies. A roadmap for imaging guided reperfusion treatment workflow in AIS is also proposed. Both systemic thrombolysis and endovascular treatment have been incorporated into the standard of care in stroke therapy. Further research on advanced imaging-based approaches to select appropriate patients, may widen the time-window for patient selection and would contribute immensely to early thrombolytic strategies, better recanalization rates, and improved clinical outcomes.
| S-EPMC5771207 | biostudies-other
Project description:mRNA therapy is a novel anticancer strategy based on in vitro transcription (IVT), which has potential for the treatment of malignant tumors. The outbreak of the COVID-19 pandemic in the early 21st century has promoted the application of mRNA technologies in SARS-CoV-2 vaccines, and there has been a great deal of interest in the research and development of mRNA cancer vaccines. There has been progress in a number of key technologies, including mRNA production strategies, delivery systems, antitumor immune strategies, etc. These technologies have accelerated the progress and clinical applications of mRNA therapy, overcoming problems encountered in the past, such as instability, inefficient delivery, and weak immunogenicity of mRNA vaccines. This review provides a detailed overview of the production, delivery systems, immunological mechanisms, and antitumor immune response strategies for mRNA cancer vaccines. We list some mRNA cancer vaccines that are candidates for cancer treatment and discuss clinical trials in the field of tumor immunotherapy. In addition, we discuss the immunological mechanism of action by which mRNA vaccines destroy tumors as well as challenges and prospects for the future.
| S-EPMC9201022 | biostudies-literature