Autoimmune Disease Series--
Multiple Sclerosis
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) characterized by a multifocal distribution of white matter in the CNS and remission relapses during the course of the disease, usually involving periventricular white matter, optic nerves, the spinal cord, the brainstem, and the cerebellum.
The pathologic features of multiple sclerosis include inflammatory cell infiltration, neuronal degeneration, axonal damage, and reactive gliosis. Clinical symptoms vary from person to person and may include visual and motor nerve abnormalities, sensory abnormalities, weakness, spasticity, urinary dysfunction, and mild cognitive symptoms, the severity and type of which depend on the areas of the brain and spinal cord affected. Globally, the prevalence of MS is about 3/100,000 with about 3.5 million patients.
Therapeutic drugs for multiple sclerosis mainly include immunosuppressants and immunomodulators, which are able to alleviate the symptoms and slow down the progression of the disease to a certain extent, but it is still difficult to achieve myelin regeneration and neuronal regeneration. The main drug development targets are listed below:
- CD20 (MS4A1): CD20 is a marker on the surface of B cells and their precursor cells. By targeting CD20, antibody-dependent cytotoxicity and complement-mediated cytotoxicity can be induced, thereby removing B cells and attenuating the inflammatory response to MS. Ocrelizumab is a monoclonal antibody analog that targets CD20 to clear B cells. Clinical trials have shown significant efficacy of Ocrelizumab in relapsing or primary progressive MS.
- CD40L (CD40LG): In MS, aberrant activation of the CD40/CD40L pathway may result in the immune system mistakenly attacking the myelin sheaths of the central nervous system, thereby triggering inflammation and injury.CD40L plays an important role in regulating the interactions of T-cells with other immune cells, particularly B-cells and antigen-presenting cells, through its interactions with its receptor, CD40. Frexalimab is a monoclonal antibody targeting CD40L that blocks the co-stimulatory CD40/CD40L cell pathway necessary for the activation and function of adaptive (T and B cells) and innate (macrophages and dendritic cells) immune cells without depleting lymphocytes, and has already achieved positive clinical results. achieved positive clinical results.
- IL17A: IL-17A, as a pro-inflammatory factor, recruits immune cells to the site of inflammation by inducing the expression of chemokines and produces a synergistic effect with other cytokines, such as TNF and IL-22, which together contribute to the exacerbation of the inflammatory response. In MS, this inflammatory response may lead to the destruction of myelin in the central nervous system, which in turn triggers a series of clinical symptoms. In addition, IL-17A may further exacerbate neurological damage by affecting the activity and function of glial cells. Secukinumab is an IL-17A inhibitor that inhibits IL-17A-mediated inflammatory responses by specifically binding to IL-17A and blocking its interaction with its receptor. Studies have shown that Secukinumab significantly reduces disease activity, decreases the number of emerging inflammatory lesions, and improves clinical symptoms in patients with MS.
- IL7R: Activation of IL-7 signaling promotes T cell expansion and increases the proliferation of autoantigens, leading to autoimmune susceptibility. In MS patients, the expression level of IL-7R is usually high. By inhibiting the function of IL-7R, the IL-7 signaling pathway can be blocked, thus inhibiting T cell expansion and autoimmune response, and achieving the purpose of treating MS. Currently, in addition to anti-IL-7R monoclonal antibody ( Crebankitug ), other inhibitors targeting the IL-7/IL-7R signaling pathway are under development. These drugs may inhibit the activation of the IL-7 signaling pathway through different mechanisms, thus providing more diverse therapeutic options for MS patients.
- CD52: CD52 is a marker on the surface of monocytes and lymphocytes. Monoclonal antibodies against CD52 deplete T, B, and NK cells, especially CD4+ T cells, thereby reducing the inflammatory response in MS. Alemtuzumab is a monoclonal antibody against CD52 that depletes T, B, and NK cells. Clinical trials have shown that Alemtuzumab significantly reduces the annual relapse rate compared to interferon, but has a similar rate of disability progression. However, alemtuzumab has serious adverse effects, especially secondary to autoimmune disease.
Others such as CD49d (ITGA4), RGMA, CXCL13, CD4, CD6 are also important targets for MS drug development. Drugs against these targets are also in clinical development and have shown some efficacy.
CUSABIO has long been committed to providing researchers with high-quality proteins, antibodies, ELISA kits and other tools for scientific research reagents, and has compiled a series of popular targets related to multiple sclerosis research and related reagent products listed below for your selection:
Multiple Sclerosis Drug Targets in Development:
Multiple Sclerosis Drug Targets Related Products
● Target Proteins
Measured by its binding ability in a functional ELISA. Immobilized CD22 at 2 μg/ml can bind Anti-CD22 rabbit monoclonal antibody, the EC50 of human CD22 protein is 4.034-4.800 ng/ml.
Measured by its binding ability in a functional ELISA. Immobilized CD40L at 2 μg/ml can bind Anti- CD40L Rabbit Monoclonal Antibody(CSB-RA156386A0HU), the EC50 is 2.353-3.232 ng/ml.
Measured by its binding ability in a functional ELISA. Immobilized CD40L at 2 μg/ml can bind Anti- CD40L Rabbit Monoclonal Antibody(CSB-RA156386A0HU), the EC50 is 2.353-3.232 ng/ml.
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Measured by its binding ability in a functional ELISA. Immobilized Human IL17A at 2 μg/ml can bind Anti-IL17A recombinant antibody (CSB-RA624104MA1HU), the EC50 is 1.818-2.170 ng/mL.
Measured by its binding ability in a functional ELISA. Immobilized Human IL2RA at 2μg/mL can bind Anti-IL2RA recombinant antibody (CSB-RA011649MA1HU)，the EC50 is 2.463-3.353 ng/mL.
Measured by its binding ability in a functional ELISA. Immobilized human CD20 at 2 μg/ml can bind Anti-CD20 recombinant antibody (CSB-RA015007A1HU), the EC50 is 3.243-7.085 ng/mL.
Measured by its binding ability in a functional ELISA. Immobilized human SEMA4D at 2 μg/ml can bind biotinylated Pepinemab, the EC50 is 1.005-1.776 ng/mL
Human TNFSF13B protein Fc tag (CSB-MP897523HU1) captured on COOH chip can bind Human BCMA protein Fc tag (CSB-MP023974HU1) with an affinity constant of 39 nM as detected by LSPR Assay.
