Multiple sclerosis (MS) is a rare, progressive, inflammatory demyelinating disease of the central nervous system, characterized by temporal and spatial complexities. It manifests through recurring motor, sensory, and cognitive dysfunctions. The immune system targets the myelin sheath surrounding nerve fibers, leading to impaired neurological function and disruption of normal nerve signal transmission, resulting in corresponding symptoms. MS primarily affects the brain's white matter, spinal cord, subcortical structures, brainstem, cerebellum, and optic nerve^[1]. Without timely and effective treatment, the disease can cause muscle coordination loss, decreased visual acuity, and functional impairment.

Clinically, MS can follow two pathways: relapse and progression. Relapsing-remitting MS (RMS), characterized by periodic neurological dysfunction, is the most common type of MS. Over time, the disease tends to worsen gradually, leading to continuous progression known as secondary progressive MS (SPMS). Primary progressive MS (PPMS), which involves progression from the initial stages, affects fewer than 10% of MS patients. The incidence rate of RMS is approximately three times higher in women than in men, with an average onset age of 30 years. However, the incidence rate of PPMS does not significantly differ between men and women, with an average onset age of 40 years^[2].

The treatment of MS primarily focuses on speeding up recovery from attacks, reducing new radiographic and clinical relapses, slowing disease progression, and managing MS symptoms^[3]. Current strategies involve modifying or suppressing inflammatory processes in the peripheral immune system, blood-brain barrier, or central nervous system. Various mechanisms of action are employed, including immune cell depletion, reduction of immune cell proliferation, and inhibition of immune cell migration^[4]. 

During the early stages of the disease, the main emphasis is on symptom management, reducing disease activity, improving disability, and preventing complications. Glucocorticoids are the primary treatment option for acute attacks. Disease-modifying therapy (DMT) aims to reduce inflammation, myelin damage, and relapses, and is recommended for remission-phase treatment to limit disease progression^[5]. DMT options include oral teriflunomide, injections of recombinant human β-1b interferon, alemtuzumab, and mitoxantrone. Symptomatic treatment involves providing tailored medications for individual symptoms. For example, modafinil and amantadine can be used to treat fatigue and weakness in MS patients. Rehabilitation therapy plays a crucial role in enhancing functional impairments such as limb, speech, and swallowing difficulties. Early and appropriate rehabilitation training should be provided under the supervision of qualified physicians.

Figure 1. Targets of current disease-modifying therapies in MS^[4]

The application of disease models is essential for drug development. Experimental Autoimmune Encephalomyelitis (EAE) is a CD4+ T cell-mediated autoimmune disease characterized by specific sensitization and infiltration of mononuclear cells surrounding small blood vessels in the central nervous system, as well as loss of myelin sheaths. The EAE model is often considered the best tool for studying MS, as it closely mimics human MS characteristics.

GemPharmatech has successfully established the EAE model, which can be utilized to evaluate therapeutic efficacy.We can see from the picture, after MOG induction, the EAE score of mice in the model group was significantly increased.

Leveraging our well-established multidisciplinary platform resources, we have innovatively conducted behavioral analyses of the EAE model through an open field test. The data obtained objectively reflect the motor ability of mice and allow for the assessment of disease severity. As illustrated in the figure, compared to the control group, EAE mice exhibit weakness in their legs and tail, accompanied by a significant decrease in movement speed and distance.

Reference:

[1] Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015;15(9):545-558.

[2] Stephen L. Hauser, Bruce A.C. Cree.Treatment of Multiple Sclerosis: A Review[J].Am J Med.2020 Dec;133(12):1380-1390.

[3] https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/diagnosis-treatment/drc-20350274

[4] Bierhansl L, Hartung HP, Aktas O, Ruck T, Roden M, Meuth SG. Thinking outside the box: non-canonical targets in multiple sclerosis. Nat Rev Drug Discov. 2022;21(8):578-600.

[5] Yang JH, Rempe T, Whitmire N, Dunn-Pirio A, Graves JS. Therapeutic Advances in Multiple Sclerosis. Front Neurol. 2022 Jun 3;13:824926.