Hey, AD! Gold mine under the fog of drug research and development

The most common Alzheimer's disease is Alzheimer's disease (AD), accounting for about 60% - 80% of the cases of Alzheimer's disease It is a fatal neurodegenerative disease with progressive development Its clinical manifestations are continuous deterioration of cognitive and memory functions, progressive decline of daily living ability, and various neuropsychological symptoms and behavioral disorders Since ad is still incurable, only drug and non drug treatment can help relieve cognitive and behavioral symptoms, so the mortality caused by the disease is also very high The annual mortality report of AD from the American Center for health statistics shows that the mortality rate of the disease remains around 25 / 100000 Neglected: China's 90% undiscovered international team led by University of London Kings College researchers has published and published the findings of Alzheimer's disease incidence rate in many developing countries, including China China The results showed that the incidence rate of Alzheimer's disease in these developing countries was about two times that before China, which was close to that of developed countries, and some even exceeded that of developed countries This is surprising to those who believe that Alzheimer's disease incidence rate in developed countries is higher than that in China What's more, more than 90% of dementia cases in China have not been found According to the survey, 80% of Chinese people mistakenly believe that ad is a typical manifestation of aging, while only 59% of the world's average people have this wrong view With the aging of the world population, Alzheimer's disease is becoming a major global public health problem China has a large population base and a large number of dementia patients Unfortunately, so far, compared with cancer and other causes of great concern, the disease is still a disease easy to be ignored Incurable: two types of symptomatic drugs in view of the status quo of incurable diseases, FDA approved two types of drugs to relieve patients' cognitive symptoms One is NMDA antagonists, and the representative drug is memantine More and more evidences show that glutamatergic neurotransmitter dysfunction (especially when NMDA receptor function is damaged) will show the clinical symptoms and disease progress of neurodegenerative dementia, and memantine can block the neuronal damage caused by pathological increase of glutamate concentration, so it is widely used in patients with moderate and severe Alzheimer's disease with memory dysfunction The second type is cholinesterase inhibitor, represented by donepezil, kabaratin, galanthamine, etc these drugs can keep the high level of acetylcholine and support the nerve transmission between nerve cells by preventing the decomposition of acetylcholine, which is clinically used in the treatment of mild to moderate ad In China, the drugs for treating nervous system have always been the world of foreign enterprises According to the data of minenet, in the markets of memantine, donepezil, kabaratin and galanthamine, the share of foreign enterprises continues to rise, and domestic enterprises still have a lot of work to do in this field Misty: the road to research and development is difficult In fact, pharmaceutical workers around the world are trying to find a cure for dementia, but the risk is also huge According to the statistics of Pharma, from 1998 to 2011, the achievements of new drug research and development in more than ten years were 3-101, and the failure came face to face Is it possible for human beings to be caught? The answer is No After the failure of phase III of solanezumab, a monoclonal antibody invested more than US $1 billion by Lilly, it invested US $500 million to bet on azd3293, an oral β - amyloid precursor protein lyase inhibitor Surprisingly, the success rate of the drug is said to be only 9% Is Lilly crazy? In fact, at present, experts tend to recognize that drug intervention in the early stage of disease may be the "key" of AD treatment Therefore, if azd3293 is successful, its annual sales may reach 5-10 billion US dollars At present, only a few drugs have been approved for ad symptomatic treatment on the market, and no one can reverse the disease process In reality, the huge medical demand, coupled with the temptation of new drug sales potential, is crazy not only for Lilly, but also for Baijian Aidi Recently, the clinical trial results of biib037 showed that biib037 can reduce β - amyloid plaques in patients' brain and has a positive effect on cognition The company's share price surged 10% on the news In fact, before this, in order to achieve some success in the field of AD, last year Baijian Aidi and Japan Weicai reached a cooperation to jointly develop two kinds of ad drugs (bace inhibitor e2609 and MAb ban2401) in Weicai pipeline and two kinds of ad drugs (mAb biib037 and an anti tau mAb) in Baijian Aidi pipeline, which has a great momentum of "sticking to Qingshan and not stopping until reaching the goal" However, the reality is always inadvertently giving people a slap in the face Recently, a new study from Mayo Clinic, a well-known research institution, pointed out that the real culprit of ad is the abnormal accumulation of tau protein Although β - amyloid protein is related to the decline of cognitive function, if the two are put together, tau protein is the "bad molecule" The target of bain037 and most of the other varieties under study is amyloid beta protein Search up and down: we will not retreat before exploration Although the road of AD drug research and development is arduous and foggy, human beings have not given up and are on the way of exploration Recently, it has been found that azd0530, a failed cancer drug in AstraZeneca trial, has the potential to become a new therapy for AD The researchers found that azd0530 can antagonize an enzyme called Fyn, which is thought to block the establishment of synaptic connections between brain cells and affect the memory of patients In addition, researchers in the UK recently found that Lintuzumab, a drug that has passed human safety tests but failed to treat leukemia, may be the killer of AD The researchers speculate that Lintuzumab, as an inhibitor of CD33, may activate delayed microglia, thus reducing the risk of AD and even surpassing the protective effect of CD33 gene mutation Although the focus of the above research is still to clear the aggregation and dead cells of amyloid β, as Dean Harley, director of scientific initiative of Alzheimer's Association, said, the Mayo Clinic research does not reduce the high degree of thought that β amyloid may participate in the progress of the disease Therefore, it is necessary to study multiple methods and explore multiple targets in the condition that human beings have not mastered the "mechanism" of AD treatment In China, medical workers are also indignant in the field of AD drug research and development Huperzine A, an anti AD drug independently developed in China in the 1990s, is an outstanding representative Huperzine A belongs to alkaloids, which comes from the Senecio of huperzine family It is more selective to acetylcholinesterase than carbamate and donepezil It is clinically used to improve the memory impairment of dementia patients and brain organic diseases As early as a few years ago, the Chinese Academy of traditional Chinese medicine, Shenwei pharmaceutical and the University of Western Sydney in Australia jointly signed a major international cooperation project of traditional Chinese medicine, the international multi center clinical research cooperation agreement of serotong capsule, to carry out international clinical research on the treatment of vascular dementia and Alzheimer's disease with five new drugs, trying to explore a way in the field of AD treatment A new way of medicine internationalization It's a long way to go I'll go up and down to look for it The famous sentence in Qu Yuan's Lisao more than 2000 years ago is exactly the reality of AD drug research and development On the way to the exploration of ad therapeutic drugs, human beings will not shrink back.