Multiple sclerosis (MS), characterized by a proinflammatory and neurodegenerative process, is an inflammatory demyelinating disease of the central nervous system (CNS) that results in neuroaxonal damage. There are several types of MS, including Benign MS, Relapsing-Remitting MS (RRMS), Secondary Progressive MS (SPMS), Primary-Progressive MS (PPMS), and Malignant MS. Clinical expressions of MS vary depending on the locations of affected nerve fibers, but the most common symptoms are sensory loss, motor spinal cord symptoms, autonomic spinal cord symptoms, cerebellar symptoms, optic neuritis, trigeminal neuralgia, etc. Epidemiological data indicate that both genetic and environmental factors are important for the etiology of MS. Experimental autoimmune encephalomyelitis (EAE) is one of the most widely used models of MS. Besides, Theiler's murine encephalitis virus-induced demyelinating disease (TMEV-IDD) has been intensively used as a model for human demyelinating diseases, including MS. Demyelination induced in mice with a copper chelator cuprizone is also an important tool for MS studies.
Fig.1 B-cell mediated inflammatory pathway in MS.
B cells are important in MS because of their efficient antigen-presenting abilities. They produce cytokines that can change the microenvironment and mediate the negative effects through astrocyte populations, and they produce antibodies with potential roles in targeting ectopic lymphoid follicle like aggregates that persist long term in the brains of MS patients. The understanding of the role of B cells in MS presents opportunities for developing effective therapies. Therapeutic monoclonal antibodies (mAbs) utilized in the treatment of MS and their molecular targets are shown in Fig.2.
Fig.2 Therapeutic mAbs utilized in the treatment of MS and their molecular targets. (Dubey, 2015)
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Summary of Popular Targets in Multiple Sclerosis
|CD52||Muscarinic type 3 receptor (M3R)|
|α4-integrin||C5 complement protein|
|Leucine-rich repeat and immunoglobulin domain-containing neurite outgrowth inhibitor receptor-interacting protein-1 (LINGO-1)|
|Sphingosine-1-phosphate 1/5 receptors|
- Dubey, D.; et al. Clinical management of multiple sclerosis and neuromyelitis optica with therapeutic monoclonal antibodies: approved therapies and emerging candidates. Expert review of clinical immunology. 2015, 11(1): 93-108.