Multiple sclerosis (MS) is a major cause of disability in young adults. Following an unknown trigger (or triggers), the immune system attacks the myelin sheath surrounding axons, leading to progressive nerve cell death. Antibodies and small-molecule drugs directed against B cells have demonstrated good efficacy in slowing progression of the disease. This review focusses on small-molecule drugs that can affect B-cell biology and may have utility in disease management. The risk genes for MS are examined from the drug target perspective. Existing small-molecule therapies for MS with B-cell actions together with new drugs in development are described. The potential for experimental molecules with B-cell effects is also considered. Small molecules can have diverse actions on B cells and be cytotoxic, anti-inflammatory and anti-viral. The current B cell-directed therapies often kill B-cell subsets, which can be effective but lead to side effects and toxicity. A deeper understanding of B-cell biology and the effect on MS disease should lead to new drugs with better selectivity, efficacy, and an improved safety profile. Small-molecule drugs, once the patent term has expired, provide a uniquely sustainable form of healthcare.
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http://dx.doi.org/10.12688/f1000research.16495.1 | DOI Listing |
Sci China Life Sci
January 2025
Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Peking University Health Science Center, Peking University, Beijing, 100191, China.
Human primed pluripotent stem cells are capable of generating all the embryonic lineages. However, their extraembryonic trophectoderm potentials are limited. It remains unclear how to expand their developmental potential to trophectoderm lineages.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Hunan University, College of Chemistry and Chemical Engineering, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistr, 410082, Changsha, CHINA.
Immunotherapy is a promising cancer treatment, but its application is hindered by tumors' low immunogenicity and the difficulty of immune cell infiltration. Here, to address above issues and achieve targeted tumor treatment, we designed the first activated small molecule photosensitizer immune-prodrug HDIM based on pyroptosis, and proposed a self-amplified immune therapy strategy (SITS) for enhanced tumor therapy. HDIMcan be specifically activated by the tumor hypoxiaand then simultaneously initiate immuno-therapy and photodynamic therapy (PDT)-induced pyroptosis with NIR laser irradiation.
View Article and Find Full Text PDFBiomaterials
January 2025
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA; Department of Surgery, Houston Methodist Hospital, Houston, TX, USA; Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA. Electronic address:
Contrasting findings are presented in the literature regarding the influence of foreign body response (FBR) on drug release from implantable drug delivery systems. To this end, here we sought direct evidence of the effect of the fibrotic tissue on subcutaneous drug release from long-acting drug delivery implants. Specifically, we investigated the pharmacokinetic impact of fibrotic encapsulation on a small molecule drug, islatravir (293 Da), and a large protein, IgG (150 kDa), administered via biocompatible implants.
View Article and Find Full Text PDFNan Fang Yi Ke Da Xue Xue Bao
January 2025
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
With advances of drug design and preparation technology, the development of long-acting drugs has become an important research focus in precision medicine and chronic disease management. These drugs are designed to improve the patients' compliance and quality of life by achieving prolonged maintenance of an effective drug concentration in the body with a reduced dosing frequency. Small molecule drugs, monoclonal antibodies and nucleic acid drugs all have their own difficulties in achieving long actions, which can be especially challenging for the latter two because of their structural complexity.
View Article and Find Full Text PDFNan Fang Yi Ke Da Xue Xue Bao
January 2025
Provincial School of Clinical Medicine, Fujian Medical University; Department of Respiratory and Critical Care Medicine, Fujian Provincial Hospital of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, China.
Objectives: To identify the key genes and immunological pathways shared by type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) and explore the potential therapeutic targets of T2DM complicated by COPD.
Methods: GEO database was used for analyzing the gene expression profiles in T2DM and COPD to identify the common differentially expressed genes (DEGs) in the two diseases. A protein-protein interaction network was constructed to identify the candidate hub genes, which were validated in datasets and disease sets to obtain the target genes.
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