Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

New Drug Treatments for Osteoarthritis: What is on the Horizon?

ABSTRACT: Osteoarthritis (OA) is the most common form of arthritis, yet has historically lagged far behind rheumatoid arthritis in terms of drug development. Despite the many challenges presented by clinical trials in OA, improvements in our understanding of disease pathogenesis and a move to treat pain, as well as underlying disease process, mean there are now many new pharmacological therapies currently in various stages of clinical trials. The medical need for these therapies and the evidence for recent tissue and molecular targets are reviewed. Current therapeutic examples in each area are discussed, including both novel therapeutics and existing agents which may be repurposed from other disease areas. Some challenges remain, but opportunities for improving symptoms and disease process in OA in the clinic with new pharmacological agents would appear to be on the close horizon.

SUBMITTER: Watt FE

PROVIDER: S-EPMC6198938 | biostudies-other | 2017 Mar

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

New Drug Treatments for Osteoarthritis: What is on the Horizon?

Watt Fiona E FE Gulati Malvika M

European medical journal. Rheumatology 20170301 1

Osteoarthritis (OA) is the most common form of arthritis, yet has historically lagged far behind rheumatoid arthritis in terms of drug development. Despite the many challenges presented by clinical trials in OA, improvements in our understanding of disease pathogenesis and a move to treat pain, as well as underlying disease process, mean there are now many new pharmacological therapies currently in various stages of clinical trials. The medical need for these therapies and the evidence for recen ...[more]

PMID: 30364878

Similar Datasets

New Trends in Pharmacological Treatments for Osteoarthritis.

Project description:Osteoarthritis (OA) is the leading cause of function loss and disability among the elderly, with significant burden on the individual and society. It is a severe disease for its high disability rates, morbidity, costs, and increased mortality. Multifactorial etiologies contribute to the occurrence and development of OA. The heterogeneous condition poses a challenge for the development of effective treatment for OA; however, emerging treatments are promising to bring benefits for OA management in the future. This narrative review will discuss recent developments of agents for the treatment of OA, including potential disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics for pain relief. This review will focus more on drugs that have been in clinical trials, as well as attractive drugs with potential applications in preclinical research. In the past few years, it has been realized that a complex interaction of multifactorial mechanisms is involved in the pathophysiology of OA. The authors believe there is no miracle therapeutic strategy fitting for all patients. OA phenotyping would be helpful for therapy selection. A variety of potential therapeutics targeting inflammation mechanisms, cellular senescence, cartilage metabolism, subchondral bone remodeling, and the peripheral nociceptive pathways are expected to reshape the landscape of OA treatment over the next few years. Precise randomized controlled trials (RCTs) are expected to identify the safety and efficacy of novel therapies targeting specific mechanisms in OA patients with specific phenotypes.

| S-EPMC8085504 | biostudies-literature

New drug on the horizon for treating adenovirus.

Project description:Human adenoviruses can cause serious disseminated infections including death in immunosuppressed patients, especially pediatric allogeneic hematopoietic stem cell transplant (allo-HSCT) patients. There are no drugs approved to treat such infections. Cidofovir is used intravenously in many transplant clinics, probably with some effect, but controlled trials have not been completed. Cidofovir is an acyclic nucleoside phosphonate analog of cytidine monophosphate. Following conversion to its diphosphate form within cells, cidofovir is a preferred substrate for the adenovirus DNA polymerase, leading to viral DNA chain termination. Problems with cidofovir include poor cellular uptake and nephrotoxicity. Brincidofovir, a lipid-linked derivative of cidofovir which is active against five families of double-stranded DNA viruses, represents a major advance in anti-adenovirus therapy. It is administered orally, taken up readily by cells followed by release of cidofovir within cells, and is not nephrotoxic. Brincidofovir, under development by Chimerix, Inc., is being evaluated against adenovirus infections in transplant patients including allo-HSCT patients in a phase III clinical trial (AdVise Study). Preliminary results indicate that brincidofovir is safe and very effective at decreasing adenovirus viremia and adenovirus-induced pathogenicity and mortality. Anti-adenovirus adoptive T cell therapy is another very promising approach to treating allo-HSCT patients as demonstrated in clinical studies.

| S-EPMC4866633 | biostudies-literature

Network medicine analysis of chondrocyte proteins towards new treatments of osteoarthritis.

Project description:Osteoarthritis (OA) is a progressive disorder with high incidence in the ageing human population that still has no treatment currently. This disorder induces the breakdown of articular cartilage, leading to the exposure and damage of bone surfaces. For a global understanding of OA development, the systematic integration of known OA-related proteins with protein-protein interaction (PPI) networks is required. In this work, the OA-related interactome was reconstructed using multiple data sources to have the most up-to-date information on OA-related proteins and their interactions. We then combined emergent concepts in network medicine to detect new unclassified OA-related proteins. The mapping of known OA-related proteins with PPI networks showed that these proteins are locally connected to each other and agglomerated in a large component. To expand this module, we applied a diffusion-based algorithm that probabilistically induces more searches in the vicinity of the seed OA-related proteins. As a result, the 10 topmost ranked proteins were connected to the OA disease module, supporting the local hypothesis. We computed structural modules and selected those that had the highest enrichment of OA-related proteins. The identified molecules show a link between structural topology and disease dysfunctionality. Interestingly, the protein Q6EEV6 was highlighted for OA association by both methods, reinforcing the potential involvement of this protein. These results suggest that similar disease-connected modules may exist in different human disorders, which could lead to systematic identification of genes or proteins that have a joint role in specific disease phenotypes.

| S-EPMC3906943 | biostudies-literature

New Treatments for Systemic Lupus Erythematosus on the Horizon: Targeting Plasmacytoid Dendritic Cells to Inhibit Cytokine Production.

Project description:Patients with systemic lupus erythematosus (SLE) often have elevated levels of type I interferon (IFN, particularly IFNα), a cytokine that can drive many of the symptoms associated with this autoimmune disorder. Additionally, the presence of autoantibody-secreting plasma cells contributes to the systemic inflammation observed in SLE and IFNα supports the survival of these cells. Current therapies for SLE are limited to broad immunosuppression or B cell-targeting antibody-mediated depletion strategies, which do not eliminate autoantibody-secreting plasma cells. Recent clinical trials testing the efficacy of IFNα neutralization in SLE have delivered disappointing results, with primary endpoints not being met or with minimal improvements, while studies evaluating antibody therapy targeting the type I IFN receptor was more successful and is currently being tested in phase III clinical studies. As many studies have supported the idea that plasmacytoid dendritic cells (pDCs) are the main source of IFNα in SLE, specifically targeting pDCs in SLE represents a new therapeutic option. Murine models suggest pDC ablation effectively ameliorates or reduces lupus-like disease development in spontaneous models of lupus and pre-clinical and phase I clinical trials support the safety of such a therapy in humans. Here we review animal studies and the current status of clinical trials targeting IFNα, type I interferon receptor and pDCs in SLE.

| S-EPMC5804747 | biostudies-literature

Hope on the Horizon: Novel Fungal Treatments in Development.

Project description:The treatment of invasive fungal infections remains challenging due to limitations in currently available antifungal therapies including toxicity, interactions, restricted routes of administration, and drug resistance. This review focuses on novel therapies in clinical development, including drugs and a device. These drugs have novel mechanisms of action to overcome resistance, and some offer new formulations providing distinct advantages over current therapies to improve safety profiles and reduce interactions. Among agents that target the cell wall, 2 glucan synthesis inhibitors are discussed (rezafungin and ibrexafungerp), as well as fosmanogepix and nikkomycin Z. Agents that target the cell membrane include 3 fourth-generation azoles, oral encochleated amphotericin B, and aureobasidin A. Among agents with intracellular targets, we will review olorofim, VL-2397, T-2307, AR-12, and MGCD290. In addition, we will describe neurapheresis, a device used as adjunctive therapy for cryptococcosis. With a field full of novel treatments for fungal infections, the future looks promising.

| S-EPMC7031074 | biostudies-literature

Symptomatic Efficacy of Pharmacological Treatments for Knee Osteoarthritis: A Systematic Review and a Network Meta-Analysis with a 6-Month Time Horizon.

Project description:IntroductionSeveral pharmacological treatments aiming at a better symptomatic control of osteoarthritis (OA) are used in daily practice but their efficacy is often disputed. The purpose of this network meta-analysis (NMA) is to assess the efficacy on pain and function of the drugs that are most widely prescribed against knee OA.MethodsMedline, Scopus, and Cochrane database of systematic reviews were searched for randomized controlled trials published up to August 2019 and assessing the efficacy of knee OA treatments using a 6-month time horizon. Pain and function changes from baseline were the primary outcomes. A Bayesian network meta-analysis was run and standardized mean differences (SMDs) with 95% credibility intervals (95% CrIs) were calculated.Results9697 references were identified and 80 RCTs were concordant with our inclusion criteria (79 studies involving 15,609 individuals reported pain outcomes and 55 studies involving 13,655 individuals reported function outcomes). A significant decrease in pain was observed for the intra-articular (IA) combination of hyaluronic acid (HA) and triamcinolone (SMD - 0.49, 95% CrI - 0.78; - 0.19), vitamin D (SMD - 0.31, 95% CrI - 0.56; - 0.06), IA HA (SMD - 0.29, 95% CrI - 0.40; - 0.17), prescription-grade crystalline glucosamine sulfate (pCGS) (SMD - 0.29, 95% CrI - 0.58; - 0.004), and prescription-grade chondroitin sulfate (pCS) (SMD - 0.26, 95% CrI - 0.44; - 0.08). Significant improvements in physical function were found with pCGS (SMD - 0.44, 95% CrI - 0.66; - 0.21), vitamin D (SMD - 0.30, 95% CrIs - 0.49; - 0.11) and IA HA (SMD - 0.21, 95% CrIs - 0.31; - 0.11).ConclusionSix months of treatment with IA HA, pCGS, pCS, vitamin D and the combination of IA HA and triamcinolone improve pain and/or physical function in patients suffering from knee OA.

| S-EPMC7716887 | biostudies-literature

Drug repurposing unveils new combinatorial treatments to treat mutant KRAS lung cancer

Project description:We report data on a drug combination with synergistic antitumor effect in KRAS-driven lung cancer. We used RNAseq to characterize the transcriptional changes elicited by each drug in a mutant KRAS lung cancer cell lines (H1792)

2023-08-10 | GSE161218 | GEO

Transcription Factor Network Reveals New Treatments for Prostate Cancer Docetaxel Drug Resistance

Project description:Overcoming drug resistance is critical increasing the survival rate for prostate cancer (PCa). In this study, we modeled docetaxel resistance using two PCa cell lines, DU145 and PC3. We conducted both single cell and bulk RNA sequencing. We constructed a transcription factor (TF) network for the docetaxel sensitive and resistant variants for all cell lines and sequencing methods resulting in 8 networks. We identified shared edges and nodes that represent a shared TF network for PCa that modeled the changes after acquiring drug resistance. Using this shared TF network, we identified drivers of the resistant phenotype. Interestingly, the network constructed from the bulk sequencing dataset revealed different TF drivers of resistance compared with the network constructed from the single cells. We validated the results constructed from the single cells to demonstrate the validity of the single cell sequenced TF network. We targeted GABPA (only identified in the single cell constructed network) and successfully re-sensitized both cell lines to docetaxel treatment. Additionally, we conducted connectivity map analysis to identify potential drugs that disrupt the resistant networks. We identified trichostatin A as a potential combination treatment using the single cell sequenced network. Combination treatment of trichostatin A and docetaxel, both in vitro and in vivo PCa models decreased tumor growth. These results suggest by analyzing a population of resistant cells, identification of drivers and novel treatments is possible.

2023-04-01 | GSE149681 | GEO

Old and New Drug Classes Expanding To Include Glaucoma Treatments.

Project description:Poor patient adherence is fueling keen interest in the development of drugs for glaucoma management. Several long-acting formulations of existing medications are in the early stages of development, as are new therapeutic classes such as guanylate cyclase activators.

| S-EPMC6065491 | biostudies-other

New drug treatments show neuroprotective effects in Alzheimer's and Parkinson's diseases.

Project description:Type 2 diabetes is a risk factor for Alzheimer's disease and Parkinson's disease. Insulin signaling in the brains of people with Alzheimer's disease or Parkinson's disease is impaired. Preclinical studies of growth factors showed impressive neuroprotective effects. In animal models of Alzheimer's disease and Parkinson's disease, insulin, glia-derived neurotrophic factor, or analogues of the incretin glucagon-like peptide-1 prevented neurodegenerative processes and improved neuronal and synaptic functionality in Alzheimer's disease and Parkinson's disease. On the basis of these promising findings, several clinical trials are ongoing with the first encouraging clinical results published. This gives hope for developing effective treatments for Alzheimer's disease and Parkinson's disease that are currently unavailable.

| S-EPMC4281420 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data