Resolution-Based Therapies: The Potential of Lipoxins to Treat Human Diseases.
Ontology highlight
ABSTRACT:
SUBMITTER: Jaen RI
PROVIDER: S-EPMC8102821 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Regulatory T cells (Tregs) are a small yet critical subset of CD4+ T cells, which have the role of maintaining immune homeostasis by, for example, regulating self-tolerance, tumor immunity, anti-microbial resistance, allergy and transplantation rejection. The suppressive mechanisms by which Tregs function are varied and pleiotropic. The ability of Tregs to maintain self-tolerance means they are critical for the control and prevention of autoimmune diseases. Irregularities in Treg function and number can result in loss of tolerance and autoimmune disease. Restoring immune homeostasis and tolerance through the promotion, activation or delivery of Tregs has emerged as a focus for therapies aimed at curing or controlling autoimmune diseases. Such therapies have focused on the Treg cell subset by using drugs to suppress T effector cells and promote Tregs. Other approaches have trialed inducing tolerance by administering the autoantigen via direct administration, by transient expression using a DNA vector, or by antigen-specific nanoparticles. More recently, cell-based therapies have been developed as an approach to directly or indirectly enhance Treg cell specificity, function and number. This can be achieved indirectly by transfer of tolerogenic dendritic cells, which have the potential to expand antigen-specific Treg cells. Treg cells can be directly administered to treat autoimmune disease by way of polyclonal Tregs or Tregs transduced with a receptor with high affinity for the target autoantigen, such as a high affinity T cell receptor (TCR) or a chimeric antigen receptor (CAR). This review will discuss the strategies being developed to redirect autoimmune responses to a state of immune tolerance, with the aim of the prevention or amelioration of autoimmune disease.
| S-EPMC7582931 | biostudies-literature
Project description:Mutated RNA splicing machinery drives many human diseases and is a promising therapeutic target for engineering and small molecule therapy. In the case of mutations in individual genes that cause them to be incorrectly spliced, engineered splicing factors can be introduced to correct splicing of these aberrant transcripts and reduce the effects of the disease phenotype. Mutations that occur in certain splicing factor genes themselves have been implicated in many cancers, particularly myelodysplastic syndromes. Small molecules that target splicing factors have been developed as therapies to preferentially induce apoptosis in these cancer cells. Specifically, drugs targeting the splicing factor SF3B1 have led to recent clinical trials. Here, we review the role of alternative splicing in disease, approaches to rescue incorrect splicing using engineered splicing factors, and small molecule splicing inhibitors developed to treat hematological cancers.
| S-EPMC6694006 | biostudies-literature
Project description:This Review provides an update on ryanodine receptors (RyRs) and their role in human diseases of heart, muscle, and brain. Calcium (Ca2+) is a requisite second messenger in all living organisms. From C. elegans to mammals, Ca2+ is necessary for locomotion, bodily functions, and neural activity. However, too much of a good thing can be bad. Intracellular Ca2+ overload can result in loss of function and death. Intracellular Ca2+ release channels evolved to safely provide large, rapid Ca2+ signals without exposure to toxic extracellular Ca2+. RyRs are intracellular Ca2+ release channels present throughout the zoosphere. Over the past 35 years, our knowledge of RyRs has advanced to the level of atomic-resolution structures revealing their role in the mechanisms underlying the pathogenesis of human disorders of heart, muscle, and brain. Stress-induced RyR-mediated intracellular Ca2+ leak in the heart can promote heart failure and cardiac arrhythmias. In skeletal muscle, RyR1 leak contributes to muscle weakness in inherited myopathies, to age-related loss of muscle function and cancer-associated muscle weakness, and to impaired muscle function in muscular dystrophies, including Duchenne. In the brain, leaky RyR channels contribute to cognitive dysfunction in Alzheimer's disease, posttraumatic stress disorder, and Huntington's disease. Novel therapeutics targeting dysfunctional RyRs are showing promise.
| S-EPMC9843046 | biostudies-literature
Project description:Skin disease may be related with immunological disorders, external aggressions, or genetic conditions. Injuries or cutaneous diseases such as wounds, burns, psoriasis, and scleroderma among others are common pathologies in dermatology, and in some cases, conventional treatments are ineffective. In recent years, advanced therapies using human mesenchymal stem cells (hMSCs) from different sources has emerged as a promising strategy for the treatment of many pathologies. Due to their properties; regenerative, immunomodulatory and differentiation capacities, they could be applied for the treatment of cutaneous diseases. In this review, a total of thirteen types of hMSCs used as advanced therapy have been analyzed, considering the last 5 years (2015-2020). The most investigated types were those isolated from umbilical cord blood (hUCB-MSCs), adipose tissue (hAT-MSCs) and bone marrow (hBM-MSCs). The most studied diseases were wounds and ulcers, burns and psoriasis. At preclinical level, in vivo studies with mice and rats were the main animal models used, and a wide range of types of hMSCs were used. Clinical studies analyzed revealed that cell therapy by intravenous administration was the advanced therapy preferred except in the case of wounds and burns where tissue engineering was also reported. Although in most of the clinical trials reviewed results have not been posted yet, safety was high and only local slight adverse events (mild nausea or abdominal pain) were reported. In terms of effectiveness, it was difficult to compare the results due to the different doses administered and variables measured, but in general, percentage of wound's size reduction was higher than 80% in wounds, Psoriasis Area and Severity Index and Severity Scoring for Atopic Dermatitis were significantly reduced, for scleroderma, parameters such as Modified Rodnan skin score (MRSC) or European Scleroderma Study Group activity index reported an improvement of the disease and for hypertrophic scars, Vancouver Scar Scale (VSS) score was decreased after applying these therapies. On balance, hMSCs used for the treatment of cutaneous diseases is a promising strategy, however, the different experimental designs and endpoints stablished in each study, makes necessary more research to find the best way to treat each patient and disease.
| S-EPMC7985058 | biostudies-literature
Project description:Gene therapy is making a comeback. With its twin promise of targeting disease etiology and 'long-term correction', gene-based therapies (defined here as all forms of genome manipulation) are particularly appealing for neurodegenerative diseases, for which conventional pharmacologic approaches have been largely disappointing. The recent success of a viral-vector-based gene therapy in spinal muscular atrophy-promoting survival and motor function with a single intravenous injection-offers a paradigm for such therapeutic intervention and a platform to build on. Although challenges remain, the newfound optimism largely stems from advances in the development of viral vectors that can diffusely deliver genes throughout the CNS, as well as genome-engineering tools that can manipulate disease pathways in ways that were previously impossible. Surely spinal muscular atrophy cannot be the only neurodegenerative disease amenable to gene therapy, and one can imagine a future in which the toolkit of a clinician will include gene-based therapeutics. The goal of this Review is to highlight advances in the development and application of gene-based therapies for neurodegenerative diseases and offer a prospective look into this emerging arena.
| S-EPMC8394447 | biostudies-literature
Project description:The global burden of chronic kidney disease (CKD) is increasing every year and represents a great cost for public healthcare systems, as the majority of these diseases are progressive. Therefore, there is an urgent need to develop new therapies. Oligonucleotide-based drugs are emerging as novel and promising alternatives to traditional drugs. Their expansion corresponds with new knowledge regarding the molecular basis underlying CKD, and they are already showing encouraging preclinical results, with two candidates being evaluated in clinical trials. However, despite recent technological advances, efficient kidney delivery remains challenging, and the presence of off-targets and side-effects precludes development and translation to the clinic. In this review, we provide an overview of the various oligotherapeutic strategies used preclinically, emphasizing the most recent findings in the field, together with the different strategies employed to achieve proper kidney delivery. The use of different nanotechnological platforms, including nanocarriers, nanoparticles, viral vectors or aptamers, and their potential for the development of more specific and effective treatments is also outlined.
| S-EPMC8001091 | biostudies-literature
Project description:Neurodegenerative diseases are characterized by irreversible cell damage, loss of neuronal cells and limited regeneration potential of the adult nervous system. Pluripotent stem cells are capable of differentiating into the multitude of cell types that compose the central and peripheral nervous systems and so have become the major focus of cell replacement therapies for the treatment of neurological disorders. Human embryonic stem cell (hESC) and human induced pluripotent stem cell (hiPSC)-derived cells have both been extensively studied as cell therapies in a wide range of neurodegenerative disease models in rodents and non-human primates, including Parkinson's disease, stroke, epilepsy, spinal cord injury, Alzheimer's disease, multiple sclerosis and pain. In this review, we discuss the latest progress made with stem cell therapies targeting these pathologies. We also evaluate the challenges in clinical application of human pluripotent stem cell (hPSC)-based therapies including risk of oncogenesis and tumor formation, immune rejection and difficulty in regeneration of the heterogeneous cell types composing the central nervous system.
| S-EPMC7699962 | biostudies-literature
Project description:Since the seminal breakthrough of treating diabetic patients with insulin in the 1920s, there has been great interest in developing other proteins and their peptide mimetics as therapies for a wide variety of other medical disorders. Currently, there are at least 60 different peptides that have been approved for human use and over 150 peptides that are in various stages of clinical development. Peptides mimetic of the major proteins on lipoproteins, namely apolipoproteins, have also been developed first as tools for understanding apolipoprotein structure and more recently as potential therapeutics. In this review, we discuss the biochemistry, peptide mimetics design and clinical trials for peptides based on apoA-I, apoE and apoC-II. We primarily focus on applications of peptide mimetics related to cardiovascular diseases. We conclude with a discussion on the limitations of peptides as therapeutic agents and the challenges that need to be overcome before apolipoprotein mimetic peptides can be developed into new drugs.
| S-EPMC8000854 | biostudies-literature
Project description:Inherited retinal diseases (IRDs) are a genetically and phenotypically heterogeneous group of genetic eye disorders. There are more than 300 disease entities, and together this group of disorders affects millions of people globally and is a frequent cause of blindness or low-vision certification. However, each type is rare or ultra-rare. Characteristically, the impaired vision in IRDs is due to retinal photoreceptor dysfunction and loss resulting from mutation in a gene that codes for a retinal protein. Historically, IRDs have been considered incurable and individuals living with these blinding conditions could be offered only supportive care. However, the treatment landscape for IRDs is beginning to evolve. Progress is being made, driven by improvements in understanding of genotype-phenotype relationships, through advances in molecular genetic testing and retinal imaging. Alongside this expanding knowledge of IRDs, the current era of precision medicine is fueling a growth in targeted therapies. This has resulted in the first treatment for an IRD being approved. Several other therapies are currently in development in the IRD space, including RNA-based therapies, gene-based therapies (such as augmentation therapy and gene editing), cell therapy, visual prosthetics, and optogenetics. RNA-based therapies are a novel approach within precision medicine that have demonstrated success, particularly in rare diseases. Three antisense oligonucleotides (AONs) are currently in development for the treatment of specific IRD subtypes. These RNA-based therapies bring several key advantages in the setting of IRDs, and the potential to bring meaningful vision benefit to individuals living with inherited blinding disorders. This review will examine the increasing breadth and relevance of RNA-based therapies in clinical medicine, explore the key features that make AONs suitable for treating genetic eye diseases, and provide an overview of the three-leading investigational AONs in clinical trials.
| S-EPMC9643766 | biostudies-literature
Project description:Degenerative musculoskeletal diseases (DMDs), including osteoporosis, osteoarthritis, degenerative disc disease, and sarcopenia, present major challenges in the aging population. Patients with DMDs present with pain, functional decline, and reduced exercise tolerance, which result in long-term or permanent deficits in their ability to perform daily activities. Current strategies for dealing with this cluster of diseases focus on relieving pain, but they have a limited capacity to repair function or regenerate tissue. Cell-based therapies have attracted considerable attention in recent years owing to their unique mechanisms of action and remarkable effects on regeneration. In this review, current experimental attempts to use cell-based therapies for DMDs are highlighted, and the modes of action of different cell types and their derivatives, such as exosomes, are generalized. In addition, the latest findings from state-of-the-art clinical trials are reviewed, approaches to improve the efficiency of cell-based therapies are summarized, and unresolved questions and potential future research directions for the translation of cell-based therapies are identified.
| S-EPMC10375105 | biostudies-literature