My Alzheimer's Journey
Part 99 - Development of Aricept
I finished yesterday’s essay (Part 98) by stating in the early 1980s, multiple neurotransmitter deficits were found in autopsy studies of seventeen patients with Alzheimer’s disease. These studies led to the discovery that Cholinesterase (ChE) inhibitors can interfere with the progression of Alzheimer’s disease (AD).
The leader of the these studies, Hachiro Sugimotohas, has a fascinating life story that highlights his brilliance and tenacity.
He was born in 1943 in Tokyo. He was the eighth child among nine children. “His mother worked at a factory in the daytime and moonlighted at home every day as the breadwinner. Even so, his family sometimes got pinched for money, and had no choice but to borrow money. She did anything she could do, including the peddling of basket clams, but I could not understand why she had to suffer." [ChuoOnline - Chuo University Gakuin Jihou, Issue 464]
Hachiro’s older brothers and sisters went to evening high school while working at daytime jobs. He abandoned his dream of becoming a poet or a novelist and entered high school studying chemical engineering. After high school, he joined Eisai, a Japanese pharmaceutical company in 1961. Hachiro chose Eisai because it was a small company with about two hundred employees. He worried that at a larger company he would be at a disadvantage due to his lack of a college degree.
At Eisai, Hachiro was immediately assigned to a new drug development team. He quickly realized that to be a full-fledged researcher, a college degree would be necessary. Developing drugs during the day and taking classes at night, Hachiro graduated from Chuo University in 1969.
At the age of 26, Eisai promoted Hachiro to Chief Researcher developing the blood pressure-lowering drug bunazosin hydrochloride (Detantol). Always humble, Hachiro credited his education at Chuo University for his success leading the Detantol team. The drug is still on the market, primarily in Japan.
Soon after the completion of Detamtol, Hachiro’s mother was diagnosed with cerebrovascular dementia. This shocking event was the catalyst for him to develop a drug to treat dementia. Sadly, his mother died during the new medicine development period. Near the end of the dementia drug development, severe side effects were discovered, and the drug development was aborted.
Hachiro transitioned to developing a new drug to treat AD.
In early 2002, Hachiro published an article in the Japanese Journal of Pharmacology explaining how Donepezil Hydrochloride (Aricept) was developed. He wrote, “the earliest known ChE inhibitors, namely, physostigmine and tacrine, showed modest improvement in the cognitive function of AD patients. However, clinical studies show that physostigmine has poor oral activity, brain penetration and pharmacokinetic parameters, while tacrine has hepatotoxic liability.”
Facing this challenge, the team led by Hachiro focused on finding a new type of acetylcholinesterase (AChE) inhibitor that would overcome the disadvantages of these two compounds. After four years of research, the team found donepezil hydrochloride (donepezil). Donepezil had the positive characteristics to effectively treat AD patients. During clinical trials, Donepezil was proven to improve cognitive function of mild to severe moderate AD patients.
To manage the stress of drug development, Hachiro practiced kendo. This is a Japanese martial art derived from samurai swordsmanship. He had started kendo in high school. Apparently, Eisai had a kendo club that was very strict. Hachiro once said that, “compared with the kendo practice, the difficulty in creating medicines seemed nothing."
The research and development of donepezil began in 1983. Donepezil (brand name Aricept) was approved by the United States FDA on November 25, 1996, for the treatment of mild-to-moderate AD. It was later approved for the treatment of severe AD in 2006, and a higher 23 mg dose was approved in July 2010.
Hachiro obtained his doctorate in pharmacology at Hiroshima University in 2002. The next year, he retired from Eisai, and became guest professor of Graduate School of Pharmaceutical Sciences, Kyoto University. For his many achievements and his exceptional leadership, he received several prestigious awards:
The Award of Science from Eisai in October 1993
The Award of Engineering from the Pharmaceutical Society of Japan in March 1998
The Special Galien Prize in the United Kingdom in April 1998
The Chemistry-Bio Tsukuba Award in May 1998
The Imperial Award for Invention in June 2002
At the age of 82, Hachiro continues to be in involved in dementia research. A few weeks ago, the Standard (an English-language free newspaper in Hong Kong) published an article listing Hachiro’s 5 daily brain health secrets:
Exercise
Independent Living (“not blindly following others’ instructions, but making your own decisions and taking action”)
Having Hobbies
Healthy Diet
Being Grateful To Family
I read that Dr. Hachiro Sugimoto could be stubborn at times. He overcame so many challenges as a child and a young man that I think he earned the right to be a bit stubborn. You can’t argue that he is a brilliant man who continues to achieve success in his endeavors.