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Application of JNK-IN-8 for preparing neuroprotective agent for dry age-related macular degeneration (AMD)

A technology for neuroprotective agents and macular degeneration, which is applied to nervous system diseases, organic active ingredients, and medical preparations containing active ingredients, etc. It can solve the problems of unclear clinical effects, complex administration methods of antibody drugs, and affecting visual circulation, etc. question

Inactive Publication Date: 2019-02-05
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

3. Therapeutic drugs for inflammation: (1) Iluvien: For chronic inflammation in GA, Alimera Sciences in the United States is conducting phase II clinical trials to study the effect of the sustained-release preparation fluocinolone acetate, and the results are still unclear; (2) for chronic inflammation in GA. The phenomenon of complement activation in dry AMD, some monoclonal antibody drugs that inhibit complement activation, such as lampalizumab, are undergoing clinical trials and have shown certain therapeutic effects on GA in phase II trials. Repeated administration may cause serious complications such as endophthalmitis; (3) ARC1905: DNA aptamer of C5 gene, proved its safety in phase I clinical trials, but its effectiveness still needs further confirmation; (4) POT-4: Inhibitor of C3, its safety has been proved by phase I clinical trials
4. Vasodilators: Aiming at the decrease of choroidal blood supply in elderly patients with AMD, vasodilators are used to increase nutrient supply and delay retinal degeneration, including (1) Alprostadil (Alprostadil) has passed clinical phase III trials, It has been confirmed that after 6 months of treatment, compared with placebo, it has the effect of delaying retinal function degeneration; (2) Sildenafil (Sildenafil) and Moxaverine (Moxaverine): non-selective inhibitors of phosphodiesterase, However, its clinical effect is still unclear
5. Therapeutic drugs for visual cycle: (1) Esulstat (Emixustat) is a non-retinoid modulator of visual cycle isomerase RPE65, which has passed phase II clinical trials; (2) visual cycle The inhibitor retinoic acid (Fenretinide) is also being studied, and its effectiveness has not yet been tested in patients
However, all visual cycle modulators may cause side effects such as night blindness due to affecting the visual cycle
6. Stem cell therapy: At present, there have been studies using stem cells to differentiate into RPE and photoreceptor cells to treat dry AMD, but their effectiveness and safety still need long-term verification
However, there is no report about the relationship between JNK signaling pathway and dry age-related macular degeneration and JNK-IN-8 can be used as a neuroprotective agent for dry age-related macular degeneration

Method used

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  • Application of JNK-IN-8 for preparing neuroprotective agent for dry age-related macular degeneration (AMD)
  • Application of JNK-IN-8 for preparing neuroprotective agent for dry age-related macular degeneration (AMD)
  • Application of JNK-IN-8 for preparing neuroprotective agent for dry age-related macular degeneration (AMD)

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Experimental program
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Embodiment

[0024] Experimental design: JNK-IN-8 was dissolved in DMSO to make a 10mg / mL stock solution. Add the pure solvent to the mother liquor one by one, ready to use: 2% DMSO + 30% PEG 300 + 5% Tween 80 + ddH 2 O.

[0025] Animal model: Excessive accumulation of all-trans retinal can cause damage and degeneration of RPE cells and photoreceptor cells. Abnormal metabolism of all-trans-retinal (atRAL) in the visual cycle is one of the key factors in the occurrence of AMD. Mutations in the Abca4 gene are the most common cause of juvenile macular degeneration in Stargardt disease, the most common inherited form of macular degeneration. ABCA4 and RDH8 are two key proteins in the visual cycle that make atRAL regenerate into 11-cis-RAL, and Abca4 - / - R8 - / -Double-knockout mice exhibited atRAL clearance impairment, RPE cell degeneration, photoreceptor cell death, lipofuscin accumulation, and complement activation. At the same time, studies have found that Abca4 - / - R8 - / - After the do...

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Abstract

The invention discloses application of JNK-IN-8 for preparing a neuroprotective agent for dry age-related macular degeneration (AMD). JNK-IN-8 interdicts a JNK signal path through specificity, inhibits photoreceptor cell death, and maintains the integrity of a retina so as to perform a function of protecting the retina. The JNK-IN-8 can effectively penetrate through a blood retina barrier in an animal experiment; the treatment function and the curative effect are obviously. In addition, medicine administration is convenient, and no obvious toxic or side effects are in the presence. Therefore,the JNK-IN-8 has a wide prospect on the aspect of the development of a medicine for treating dry AMD diseases.

Description

technical field [0001] The invention belongs to the technical field of neuroprotective agents for macular degeneration diseases, and specifically relates to the application of JNK inhibitor JNK-IN-8 in the preparation of neuroprotective agents for dry age-related macular degeneration. Background technique [0002] According to data from the World Health Organization (WHO), macular degeneration, especially age-related macular degeneration (age-related macular degeneration, AMD) is the third most common blindness in the world after cataract and glaucoma, and it is also the cause of blindness among people over 50 years old in my country. Leading cause of blindness. According to different clinical manifestations, AMD is divided into wet AMD and dry AMD. Among them, wet AMD mainly manifests as choroidal neovascularization, and anti-VEGF drugs such as pegaptanib (Pegaptanib), ranibizumab (Ranibizumab), bevacizumab (Bevacizumab), aflibercept ( Aflibercept), Conbercept (Conbercept)...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/506A61P27/02A61P25/00
CPCA61K31/506A61P25/00A61P27/02
Inventor 吴亚林廖春燕廖怿
Owner XIAMEN UNIV
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