CN-122005807-A - Application of HGF receptor inhibitor in preparation of medicine for treating/preventing myasthenia gravis

Abstract

The invention relates to the technical field of biomedicine, discloses application of an HGF receptor inhibitor in preparing a medicament for treating/preventing myasthenia gravis, provides a novel medicament for treating the myasthenia gravis, and innovatively discovers that the HGF receptor inhibitor can be used for treating the myasthenia gravis by regulating and controlling organism inflammation, relieving the progress, clinical phenotype and pathological phenotype of MG diseases.

Inventors

• XIAO FEI
• FAN RUI
• QUE WENJUN
• LU DAN
• LIU LINQI
• DONG JING
• Gan Yaoqi
• ZHANG ZHIHAN
• Jing Sisi

Assignees

• 重庆医科大学附属第一医院

Dates

Publication Date

20260512

Application Date

20260408

Claims (6)

1. Use of an hgf receptor inhibitor for the preparation of a medicament for the treatment/prevention of myasthenia gravis.
2. 2. The use according to claim 1, wherein the HGF receptor inhibitor comprises PF04217903, SU11274, crizotinib, cabozantinib, ARQ197, XL880, INC280, MGCD265 or ASP3026.
3. 3. The use according to claim 1, wherein the HGF receptor inhibitor is used in a dose of 40 mg/kg.
4. 4. The use according to claim 1, wherein the medicament is in the form of an injection, a tablet, a powder, a granule, a pill, a capsule, an oral liquid, a paste, a cream or a spray.
5. 5. The use according to claim 1, wherein the medicament further comprises one or more pharmaceutically acceptable excipients.
6. 6. The use according to claim 5, wherein the auxiliary materials comprise diluents, fillers, binders, wetting agents, disintegrants, absorption enhancers, surfactants, adsorption carriers, lubricants and sustained-release agents which are conventional in the pharmaceutical field.

Description

Application of HGF receptor inhibitor in preparation of medicine for treating/preventing myasthenia gravis Technical Field The invention relates to the technical field of biomedicine, in particular to application of an HGF receptor inhibitor in preparing a medicament for treating/preventing myasthenia gravis. Background The statements in this section merely provide background information related to the present disclosure and may not constitute prior art. Myasthenia gravis (MYASTHENIA GRAVIS, MG) is an autoimmune disease, and the core pathological mechanism is the failure of autoantibodies produced by abnormal activation of autoreactive B cells to bind to acetylcholine receptors or functionally related molecules on postsynaptic membranes at the neuromuscular junction (NMJ). Although it is still a rare disease, its incidence increases year by year and about 20% of patients progress to the myasthenia gravis crisis within 2 years, endangering life. The existing treatment of myasthenia gravis adopts immunoregulation medicines, but the existing immunoregulation medicines (such as glucocorticoids and cyclophosphamide) have limited curative effects and obvious side effects, the therapies targeting B cell markers such as CD20/CD19 and the like cannot cover progenitor cells, partial plasmablasts and long-life plasmablasts, the effects on AChR antibody positive patients are insufficient, and complement inhibitors mainly act on downstream links and cannot clear abnormally activated B cells or correct organism immune imbalance, and meanwhile, the infection risk is increased. Therefore, development of new therapeutic drugs is urgently required. Disclosure of Invention The invention aims to provide a novel myasthenia gravis treatment drug aiming at the problem of deficiency of the existing myasthenia gravis treatment drug. The technical scheme of the invention is as follows: The invention provides application of an HGF receptor inhibitor in preparing a medicament for treating/preventing myasthenia gravis. According to a preferred embodiment, the HGF receptor inhibitor comprises PF04217903, SU11274, crizotinib, cabozantinib, ARQ197, XL880, INC280, MGCD265 or ASP3026. According to a preferred embodiment, the medicament is in the form of an injection, a tablet, a powder, a granule, a pill, a capsule, an oral liquid, a paste, a cream or a spray. According to a preferred embodiment, the HGF receptor inhibitor is used at a dose of 40 mg/kg. According to a preferred embodiment, the medicament further comprises one or more pharmaceutically acceptable excipients. According to a preferred embodiment, the auxiliary materials include diluents, fillers, binders, wetting agents, disintegrants, absorption enhancers, surfactants, adsorption carriers, lubricants and slow-release agents which are conventional in the pharmaceutical field. Compared with the prior art, the invention has the beneficial effects that: 1. the invention discloses application of an HGF receptor inhibitor in preparing a medicament for treating/preventing myasthenia gravis, and the invention discovers that the HGF receptor inhibitor PF04217903 can relieve the progress, clinical phenotype and pathological phenotype of MG diseases by regulating and controlling organism inflammation by feeding the HGF receptor inhibitor PF04217903 to the internal mouth of an EAMG rat model. Drawings FIG. 1A shows the relationship between protein expression and onset of Myasthenia Gravis (MG) in the unadjusted Cox proportional-risk regression model, and B shows the relationship between protein expression and onset of Myasthenia Gravis (MG) in the age-and sex-adjusted Cox proportional-risk regression model; Fig. 2a is a visual wien plot of the intersection between a disease-associated protein and a pharmaceutically acceptable target protein, and B is a mendelian randomization analysis using the Clump method (r 2 =0.2); Fig. 3a shows a mendelian randomization analysis using the Clump method (r 2 =0.001), B shows a relationship between Hepatocyte Growth Factor (HGF) and myasthenia gravis for a forest map, based on the results of the UK Biobank cohort study and mendelian randomization study, respectively (in the Cox proportional risk model of UK Biobank, the effect amount is expressed as a risk ratio (HR), reflecting the correlation of event occurrence times; in the MR analysis of drug targets, the effect amount is expressed as a ratio (OR), reflecting the causal relationship under the MR hypothesis); in FIG. 4, the relationship between HGF and prognosis of MG patients is verified in cross-sectional cohorts, wherein A is the plasma HGF levels of healthy control, ocular MG and broad MG patients, B is the plasma HGF levels of healthy control, MG patients with thymus abnormalities and MG patients without thymus abnormalities, C is the ROC curve and AUC value of HGF plasma levels used to distinguish MG from healthy control, D is the diagnostic performance assessment of HGF plasma levels in diagn