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June 09, 2020

Investigator-initiated clinical trial for familial Alzheimer's disease

Haruhisa Inoue, Professor, Center for iPS Cell Research and Application (CiRA), Kyoto University, along with Hidekazu Tomimoto, Professor, Department of Neurology, Mie University Graduate School of Medicine, and Haruhiko Banno, Associate Professor, Kyoto University Hospital, is leading a new investigator-initiated clinical trial to study safety and efficacy of TW-012R (bromocriptine, Towa) for Alzheimer's disease patients with mutations in presenilin-1 gene1). This study consists of an initial double-blind trial period2) and the latter open-label trial period2).

A new clinical trial notification was approved by the Pharmaceuticals and Medical Devices Agency (PMDA), and the clinical trial starts at the participating institutes.

Background Information

Alzheimer's disease is a neurodegenerative disease due to progressive damage and death of brain cells; a brain size shrinks progressively. Patients suffer in most cases cognitive disorder such as memory loss, forgetting things including date and place etc. More than a half of dementia cases is caused by Alzheimer disease with an increase its number as societies age worldwide. Currently only symptomatic treatment is available and pharmacological treatments to cure the disease is desperately awaited.

CiRA Junior Associate Professor Takayuki Kondo and Prof. Inoue have prepared iPS cells derived from Alzheimer's patient and differentiated them into cortical neurons3) to screen efficacy of medicinal compounds. Many of these agents have been marketed as approved medicine for treating other diseases. One of the main causes of Alzheimer's disease is an accumulation of amyloid beta protein in the brain. Thus, agents that abbreviate its accumulation will be effective for Alzheimer disease. Our screening4) results identified bromocriptine with the most potent effect among the screening compounds. Bromocriptine is an approved medicine with indications Parkinson's syndrome and pituitary disorders such as hyperprolactinaemia in Japan.

See "iPSC trials and informatics find new drugs for Alzheimer's disease" for information of the method and results in the paper by Kondo and Inoue.

Information of clinical trial by the Japan Registry of Clinical Trials:
Organization of the clinical trial

1) Principal Investigator: Haruhisa Inoue, Professor, Dept. of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, and Institute for Advancement of Clinical and Translational Sciences (iACT), Kyoto University Hospital

2) Coordinating Investigators: Hidekazu Tomimoto, Professor, Department of Neurology, Mie University Hospital, and Haruhiko Banno, Associate Professor, iACT, Kyoto University Hospital

3) Clinical Trial Coordination Office: Taro Okunomiya, Yoko Amino and Haruhiko Banno at iACT, Kyoto University Hospital

Other supporters of the clinical trial

Time Therapeutics, Inc. (Toshifumi Watanabe, President and CEO), a start-up company from Kyoto University, provides financial support.

Towa Pharmaceutical Co., Ltd. (Itsuro Yoshida, President) provides Bromocriptine and placebo.

Glossary

1) Familial Alzheimer's disease with presenilin 1 gene mutations.
The vast majority of Alzheimer's disease cases (>95 %) are sporadic. However, mutations in presenilin 1, along with mutations in presenilin 2 and amyloid beta protein precursor, are found in the majority of the remaining familial cases. Most of the patients with familial Alzheimer's disease with presenilin 1 gene mutations show symptoms of dementia before their 50th birthday, and progression of the disease is relatively fast.

2) Double-blind, open-label clinical trial
Double-blind trials describe the circumstance in which neither the investigators nor the patients know which group received the drug and which received the placebo. In an open-label study, both parties know which group received the drug and which received the placebo.

3) Cortical neurons
These neurons in the brain are responsible for higher-order function such as thinking, reasoning and memory, along with perception and voluntary movement.

4) Screening
A test that identifies from a large number of compounds those with possible therapeutics effects.

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