Seoul, May 10, 2001 – With 280,000 people over the age of 65 in Korea and four million American suffering from Alzheimer's disease, it is a serious disease being one of the four major causes of elderly death. Domestic researchers have discovered a new compound effective in the prevention and treatment of Alzheimer's disease and the result has been published in a renowned foreign academic journal. If the compound is commercialized, it will open a path for a Korean company to enter the global Alzheimer's disease treatment market which reaches US $200 billion or KR \260 trillion ($1=\1,300) in size.
According to latest issue of British Journal of Pharmacology (www.brjpharmacol.org), an official academic journal of the British Pharmacology Society, Hallym Medical University's Institute of Natural Medicine (Director: D.K. Song, Ph.D.) and a domestic biotech venture company, Scigenic Co., Ltd. (C.E.O.: H.S. Lee) succeeded in separating ferulic acid from the natural extract INM-176. Result of administering this compound to animal subjects for four weeks showed FA's potent neuro-protective effect against ©¬-amyloid, a toxic substance known to cause Alzheimer's disease. Furthermore, the new compound has shown to have antioxidant effect against aging brain cells.
Such finding was made as a result of Scigenic Co., Ltd. and Hallym University's Institute of Natural Medicine's joint research to reaffirm INM-176's efficacy in prevention and treatment of Alzheimer's type dementia. INM-176 is a natural extract discovered from a plant grown domestically. For the purpose of developing a new drug against Alzheimer's disease, Scigenic and its research team have made an effort to separate single compounds from INM-176. In addition to FA, many candidate compounds have been also discovered and systematic researches are under way for new drug development. INM-176 has shown remarkable result in the pre-clinical test using animal subjects, as well as human subjects in preliminary clinical test conducted in Korea. Currently, INM-176 is commercialized and sold in Korea as special nutrition product under the brand name, 'Alzhima 176'.
Scigenic's psychiatric specialist Dr. Jae Gyeong Kim Ph.D. said, "Much study has been done on Alzheimer's disease and ©¬-amyloid's role in the onset of Alzheimer's type dementia is a pathologic hallmark most recognized by the academic community. Similarly, how to effectively block ©¬-amyloid has been a key issue in treating Alzheimer's disease." "The publication of our research result is meaningful in the sense that it presented a possibility of developing a new drug that fundamentally treats Alzheimer's disease", he added.
©¬-amyloid is a toxic substance that is produced by the degeneration of brain cells. It is widely known that the accumulation of ©¬-amyloid causes loss of memory and progresses to Alzheimer's type dementia. The currently available treatments on the market, rather than fundamentally blocking ©¬-amyloid, delays the declining concentration of Acetacholine so as to slow the memory retardation and temporarily alleviate major symptoms. Similarly, while some improvement was shown at the early stage of administration it failed short of treating the disease from its origin.
Domestic researchers' progress of discovering a single compound that fundamentally block ©¬-amyloid and prevent oxidation of brain cells is being credited for opening a new path in the prevention and treatment of Alzheimer's disease. With the success in separating the single compound, it is expected that the new drug development will shift into high gears.
According to the study done by domestic researchers under the title, 'Protection against ©¬-amyloid peptide toxicity in vivo with long-term administration of ferulic acid', they divided lab rats in two groups with ten in each group. One group was treated with the new compound FA for four weeks and the other was not. After four weeks, ©¬-amyloid was administered via intracerebroventricular(i.c.v.) injection to both groups and various memory tests were conducted. The result showed that the group pretreated with the new compound performed significantly better than the other group in terms of memory and cognitive skills.
Currently there are approximately 280,000 patients suffering from Alzheimer's disease in Korea and the number is expected to reach 400,000 by the year 2002 (Korea Ministry of Health and Welfare). In the case of U.S., there are approximately 4 million people suffering with Alzheimer's disease and that number is expected to rise to 14 million by the year 2050. Globally, there will be approximately 22 million patients by 2025(U.S. Alzheimer's Association: www.alz.org).
The aging society can be responsible for the sharp increase in the number of Alzheimer's type dementia patients around the world. In other words, increase in average life expectation is fueling the number of elderly and the Alzheimer's disease patients. According to the latest statistic by FAO, the population increase of people over 60 years of age is taking place all over the world, where in Asia, in particular, the proportion of seniors over 60 years of age is predicted to rise from 8% in year 2000 to 25% by year 2050 (www.fao.org/sd/2001/PE0403a_en.htm).
There is a close correlation between aging and onset of Alzheimer's disease. In the case of Korea, 15% of people between 75-79 years of age and 39% of people over 80 years of age are suffering from Alzheimer's disease. While females are more prone to the disease than males, there is no exact reason to explain other than that decrease in female hormone during menopause is likely to be the case.
The British Journal of Pharmacology is a drug clinical and research science journal belonging to the Nature Publishing Group, which also publishes a scientific journal, Nature. It is also an official journal of the British Pharmacological Society (www.brjpharmacol.org).
New possibility of treating Alzheimer's disease from its origin
The single compound, FA, jointly developed by Hallym Medical University Institute of Natural Medicine and Scigenic Co., Ltd. is fundamentally different from existing Alzheimer's disease treatments. The drugs developed to date only functions as far as alleviating dementia symptoms by maintaining constant level of neurotransmitters in the brain. On the other hand, the newly discovered compound systematically blocks ©¬-amyloid toxicity before it damages brain cells.
According to the Hallym University Institute of Natural Medicine's study results by recently published in British Journal of Pharmacology, oral administration of FA for four weeks to mice effectively blocked ©¬-amyloid toxicity and hardly caused memory loss. The mouse without any pretreatment of FA, on the other hand, exhibited a sharp decrease in memory skills.
US $200 billion global Alzheimer's disease market
According to the report, 'Strategic Healthcare Market Analysis' by Frost & Sullivan, a U.S. market research firm, the Alzheimer's disease treatment market has experienced an average annual growth of 32.2% and its size will reach $2.4 billion by year 2006. The number of Alzheimer's disease patients will double by year 2030 and experience an enormous increase of 350% to 14 million patients by year 2050. Frost & Sullivan also added that patients who are disappointed with simple memory enhancers are looking forward to the development of new drugs. The global market size for Alzheimer's disease treatment including the cost of nursing and caring reaches an astounding US$200 billion.
Current Alzheimer's disease treatments
Japan's Eisai Co. with its product, Aricept, is currently dominating the global Alzheimer's disease market. There are also Cognex by U.S.'s Park Davis and Excelon by Novartis, which are closely following the lead by Aricept. If the single compound developed by D.K. Song's team and Scigenic can gain U.S. FDA approval for a new drug, it would make possible for a domestic company to enter the rapidly expanding global Alzheimer's disease market.
Animal Tests using Ferulic Acid
The new compound INM 176 has reached the preclinical test stage of development. Using lab mouse, the efficacy and safety of the single compound is being extensively tested. Preclinical test takes place before the clinical test, which is done on human subjects. The result of the preclinical test determines whether or not the clinical test will be carried out. In other words, only the compounds that "passed" the efficacy and safety test can be eligible for clinical trials. Only with the successful results obtained from 1st, 2nd, and 3rd stage of clinical trials can INM 176 be registered as a new drug. Currently, INM176 is near completion of the preclinical testing taking place in Korea. In efficacy and safety tests, the new compound is showing very optimistic results.
1) Passive avoidance test
A shuttle box, sized approximately 50 x 15 x 40cm is used. The box is divided into two areas by a wall with a small opening at the bottom. The opening is designed so that when a mouse goes from one area to the other, the door will shut automatically. One of the areas is equipped with an electrifiable grid on floor.
After placing a bright light in one area and releasing a mouse inside, it will momentarily observe the surrounding before dashing into the dark area through the opening. As soon as the mouse enters the dark area, the door will shut close and 0.25mA of electric current will flow along the stainless grid on the floor for one second, applying a foot shock to the mouse.
Latency time is measured from when the mouse is released into the bright area to the point when the door is shut close following the entrance into the dark area. The subject animal will subsequently remember the relation between the dark area and the electric foot shock. When the same subject animal is placed in the box again after 24 hours, it will exhibit some hesitation before going into the dark area. Measurement and comparison of the latency time between the control and test group will be made.
2) Y-maze task
Y-shape maze measurement device has three arms (close-end pathway) forming he shape of an alphabet 'Y', and each arm has identical measurement of 25x14x5cm. At the end of one arm, the mouse is first placed facing the close-end of the pathway and it is allowed to freely move around for 8 minutes. When the rear foot of the animal crosses the entrance of the arm, it is counted as an arm entry and the movement of the subject is carefully recorded. The movement of the subject is shown as the number of alternations and one alternation is made when the subject makes consecutive entries in all three arms. Spontaneous alternation behavior is the percentage of the total number of arm entries over alternation number of arm entries.
3) Water maze task
A cylindrical water tank measuring r100cm x h35cm, filled with 23¡É water with 15cm depth is prepared. Milk powder is added to cloud the water so that the platform (r4.5cm x h14.5cm) placed below the surface of the water will be kept out of sight. When using a mouse, the platform is placed in the center of one of the fan-shaped quadrants in the bottom of the tank, and the top of the platform must sit 0.5cm below the surface of the water. There will be a special mark in the lab with which the subject can reference the location of the platform.
Training trial will take place 3 times a day for 5 days. When the mouse locates the platform, it will be allowed to remain on the platform for 10 seconds, after which it will be taken to the cage. Five minutes later, the next trial will take place. If the subject is unable to locate the platform with 120 seconds, then the subject is manually placed on the platform for 10 seconds before ending the trial. For the test subjects that completed this training, probe tests will be conducted 24 hours after the last training trial. During this test, the platform is removed from the tank and the subject is allowed to search for the platform for 90 seconds.
Here, measurement is taken for the total time the subject swims around the quadrant where the platform was previously located, and this figure is expressed in percentage.
What is Dementia?
Originating from the Latin word meaning 'out of mind'. Psychiatric interpretation of dementia commonly refers to a syndrome characterized by multiple cognitive defects that include impairment in memory without the impairment in consciousness. Dementia is not a disease with a single symptom. It causes a wide range of cognitive impairment in general intelligence, learning, memory, language, problem solving, perception, concentration, and judgment.
Causes of Dementia
Dementia is generally caused by the chronic or progressive ailment of the brain. Degeneration, regression and metamorphosis of brain tissue, infection in the central nervous system (neurosyphilis, tubercular meningitis, viral encephalitis, etc.) cerebrovascular infarction, head trauma, toxic metabolic impairment, and Parkinson's disease are known to be the main causes of dementia.
The waste matter ©¬-amyloid is known as the main cause of Alzheimer's disease. Although many drugs have been attempted as a treatment but there has not been any with proven efficacy thus far. The acetylcholineesterease inhibitor, which works on the neurotransmitter acetylcholine is the only treatment used against the disease. While this drug has shown some improvement in the cognitive skills, it has no effect in the progression of the disease.
Types of Dementia
There are three types of dementia: Alzheimer's type dementia, vascular dementia, and combination type. 50-60% of dementia patients over the age of 65 suffer from Alzheimer's disease, 15-30% vascular dementia, and the remaining 10-15% suffer from a combination of the two in Korea. Vascular dementia is caused by alcoholism, depression and folate deficiency, and majority of the cases can be reversed by treating its main cause.
Alzheimer's disease patients take up over 50% of all dementia patients and people commonly think of it as senility. It is rare to have an onset before the age of 45 and the chance of suffering from the disease increases with the age. Because of the slow progression, by the time the family members recognize the symptoms it may have already progressed considerably.
When the brain of an Alzheimer's disease patient is observed with a microscope, accumulation of ©¬-amyloid inside the brain can be found. It is known that the accumulation causes infection, which in turn causes necrosis of the brain cells, thereby leading to the onset of Alzheimer's disease. Alzheimer's disease threatens 8.3% of all seniors over the age of 65 who are prone to many ailments. In year 2000, Alzheimer's disease is classified as four major causes of elderly death and its seriousness is being recognized around the world.
Social cost of Alzheimer's disease
The pain and suffering of Alzheimer's disease do not limit themselves to the burden of the patients. There are considerable cost and suffering on the part of the families and relatives as well. According to the statistics by U.S. Alzheimer's association, 4 million patients and 19 million of their families and relatives suffer together from the disease.
Alzheimer's disease does not accompany any complication. Instead, the patient's 5-7 years of survival after the onset inflicts a tremendous amount of nursing costs. In the case of Korea, the monthly cost of senior nursing homes can run as high as KRW1,000,000-1,500,000. In-patient care at a hospital with a personal nurse will cost as high as 2,500,000 won per month.
Study has found that Alzheimer's disease rank third after heart diseases and cancer in terms of the social cost in the U.S. The cost of treating the disease totals over $100 billion. The economic loss and accompanied cost reaches as high as $33 billion. Last year alone, U.S. government spent $466 million in research cost.
Reference data: Status of Alzheimer's disease patients
- 280,000 people, approximately 8.3% of people over 65 years of age are diagnosed as Alzheimer's disease patients.
Number of Patients (2000)
Classification Percentage Number of patients
Total 8.3% 279,000
Advanced 1.1% 38,000
Intermediate 2.3% 76,000
Mild 4.9% 165,000
Korea Institute for Health and Social Affairs, 'Alzheimer's disease management and mapping development research', 1997
Scigenic Co., Ltd.
Scigenic Co., Ltd. is a biotechnology incubation company that specializes in new drug discovery and development. While the company is in the process of registering as a new drug, INM176, a compound proven effective in the prevention and treatment of Alzheimer's disease, other successful projects such as painkiller, anticancer, and arthritis treatment are also in the pipeline.
Scigenic has an affiliate company, Scigen Harvest Co., Ltd., that specializes in the development of plant genetic engineering technologies. Last October, using gene transformation technology the company, together with a team led by Prof. Ja O. Guh of Chonnam National University, successfully developed a transgenic rice plant with an average of 20%, up to a maximum of 26% yield increase. While Scigen Harvest also developed a new gene transformation method using bundled acupuncture needles last March, it was once again in the spotlight in April when the company announced that it has deciphered a gene related to plant's self-defense. Scigen Harvest is also handling other genetic engineering projects including the development of herbicide-, pest-, as well as stress-resistant crops.
Hallym Medical University, Institute of Natural Medicine
- An affiliate research center of Hallym Medical University established in 1991.
- Established for the purpose of researching natural compound¡¯s pharmaceutical properties and development of pharmaceutical and functional foods.
- The center's main activity is to focus in basic and clinical research to promote the development of pharmaceutical and functional foods.
- Basic research, development research, and clinical research department work together to conduct research of natural and synthetic compounds and their effects in the central nervous system.
- The center currently possesses 300 herbal crude extracts and 500 compounds separated from natural plants.
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Contact:
Jong-Bin Yoon / Scigenic Co., Ltd.
Office: (822) 3442-6744
Fax: (822) 3442-6747
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Discovery made for a compound preventing Alzheimer¡¯s Disease 
