[Medicine heaven and earth] Alzheimer's disease has become the fourth leading cause of death for the elderly. Will radical drugs be available?

On September 20, the notice of the general office of the National Health Commission on printing and distributing the core information of Alzheimer's disease prevention and intervention was released on the website of the Chinese government The purpose of the notice is to enhance the awareness of Alzheimer's disease prevention in the whole society, push forward the prevention gateway, improve the level of prevention knowledge, reduce the growth rate of Alzheimer's disease and improve the health level of the elderly The document specifically emphasizes that patients should be treated actively Drug treatment and non drug treatment can help patients improve cognitive function, reduce complications, improve quality of life, and reduce the burden of caregivers Under the guidance of professionals, non drug therapy such as sensory stimulation, physical and intelligent exercise, music therapy and environmental therapy can be carried out However, I think the main reason for the current large-scale Alzheimer's disease is the lack of drug treatment, which also shows that the market space is huge Once the ad is successfully conquered, it must be accompanied by huge profits and academic research mileage As we all know, Alzheimer's disease (AD) is a neurodegenerative disease that seriously threatens the health of the elderly In the decades since its discovery, no drugs have been found that can cure or delay the disease process Progressive cognitive impairment and intellectual impairment, accompanied by emotional and behavioral abnormalities, not only make patients suffering, but also make their families feel anxious According to the epidemiological survey, there are about 24 million people suffering from the disease in the world, and it is estimated that by 2050, the number of patients will be close to 100 million The disease has become the fourth leading cause of death in the elderly following cardiovascular disease, tumor and stroke Therefore, there is an urgent need for an accurate drug to treat AD in the market at present If only the prevention index does not cure the root cause, it can only delay the growth of the base number from the basic situation At present, the only ad drugs approved by FDA are memantine and AChEIs, but none of them can reverse the disease process Although a variety of natural pharmaceutical ingredients have good curative effects on ad, more high-quality pharmacological and clinical studies are needed to confirm their effects In China, the only difference between the treatment selection of Alzheimer's disease and FDA approved drug treatment is that traditional Chinese medicine and other treatment drugs are allowed to be used as auxiliary treatment mode when the patient is informed It indirectly provides a platform for clinical data collection and drug discovery of natural drug treatment effect, after all, there is no attempt to know the specific method Current treatment drugs AChEIs, as one of the two first-line drugs for the treatment of mild to moderate AD, has the effect of inhibiting cholinesterase, reducing the hydrolysis of ACh, improving the level of ACh between synapses in the brain of patients, improving the cognitive function of patients with mild to moderate AD, and has been widely recognized by all sectors of the society The products mainly include donepezil, kabaratin, galanthamine and huperzine a Donepezil: according to incomplete statistics, the sales volume of donepezil's sample hospitals reached 2.3 billion yuan in 2018, with huge market space It is the mainstream treatment drug and widely exists in the hospital system at home and abroad Since the introduction of the consistency evaluation system for generic drugs, there are two enterprises that have passed the consistency evaluation, namely Zhejiang Huahai and Chongqing Zhien, which are also the two enterprises with the highest market share Kabaradin: kabaradin currently has two manufacturers, Novartis pharmaceutical and Zhejiang Jinghua, with good market sales According to the data of winning the bid from January to September 2019, the lowest price of Zhejiang Jinghua is 15 yuan, which is equivalent to 1 / 2 of Novartis It has a great price advantage, which is just in line with the substantial reduction of drug unit price by the state, and the sales quota may increase Galanthamine: galanthamine is mainly used to treat myasthenia gravis, progressive muscular dystrophy, dyskinesia, etc It is easy to penetrate the blood-brain barrier, but because of its strong central role, it can also be used to treat Alzheimer's disease The national bid winning situation of each drug, dosage form, number of bid winning enterprises, regions and enterprises are shown in the table below: from January to September 2019, there are four bid winning enterprises: Zhejiang Jinhua Kangenbei bio Pharmaceutical Co., Ltd takes the largest proportion Huperzine A: according to the statistical data, the sales quota of huperzine A reached 13.4 million yuan in 2016 The dosage form distribution of the enterprise: 6 drug manufacturers, 9 tablets, 3 capsules, 1 injection and 1 powder The main types of bid winning in China are tablets, capsules and injections: from January to September 2019, the number of bid winning enterprises in Shanghai Fudan Fuhua pharmaceutical industry reached 5 provinces, ranking first in the list: memantine: Memantine is another first-line drug approved by FDA to treat AD, because of its less adverse drug reactions, single therapy can improve behavior, cognition, daily life and overall function, and AD patients have better tolerance It is considered to be the most effective ad treatment drug at present Because of its limited clinical efficacy, the combination of ACEIs and ACEIs has a better effect on AD patients Therefore, it has aroused widespread concern and controversy in society and academia At present, the initial sales volume of memantine in 2018 is about 2.9 billion yuan In the past year, there are 14 clinical trials about memantine The dosage forms of the manufacturers are: 3 APIs, 2 tablets and 2 oral solutions (see the database of pharmaceutical intelligence for details) From January to September 2019, according to the bid winning database, memantine hydrochloride tablets are the best-selling In the paper "new drug discovery of anti Alzheimer's disease re location based on global drug data", it is pointed out that it is an important strategy to actively find multi-target targeted ligand (mtdl) that can act on multiple ad related targets at the same time In the research, we predict and mine the global drug database, and select 13 anti AD drug targets to analyze Although the pathogenesis of ad is complex and unclear, a large number of biological targets with potential therapeutic effects have been identified, including: β amyloid protein, tau protein, cholinergic receptor, glutamate receptor, 5-hydroxytryptamine receptor, dopamine receptor, noradrenaline receptor, acetylcholinesterase, butyrycholinesterase, α -, β - and γ - secretory enzymes, monoamine oxidase A and monoamine oxidase B, etc Through a variety of screening tests and analysis, the research direction of AD treatment drugs in the future has a new guidance Conclusion rosiglitazone has obvious neuroprotective effect and is considered to be a potential drug for the treatment of AD Secondly, more importantly, agomelatin can act on HTR2A, adora2a, ache, BACE1, PTGS2, gabrg1, MAOB, sigma R1 and ESR1, which indirectly indicates that agomelatin may repair cholinergic system dysfunction, 5-hydroxytryptamine system dysfunction, glutamine / GABA system dysfunction, clear β - amyloid protein, inhibit oxidative stress, neuritis, etc Multi target and multi-channel to play the role of anti ad In this way, agomelatin is likely to become a potential multi-target drug for the treatment of AD, once its in vivo and in vitro activity is further verified Agomeladine can play the role of anti ad through multiple targets and multiple ways, which can provide an important information basis for the in-depth study of new anti ad drugs, and also provide reference for the reorientation of other drugs on the market Content source: new drug discovery of anti Alzheimer's disease re location based on global drug data, current research on drug treatment of Alzheimer's disease, 2018 China dementia and cognitive disorders diagnosis and treatment guide Statement: this opinion only represents the author, not the position of yaozhi.com, welcome to exchange and supplement in the message area; if you need to reprint, please be sure to indicate the author and source of the article.