Kinopharma

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Central nervous system disease curative medicine

We kinopharma aim to develop drugs that treat central nervous system diseases.

What are Down’s syndrome and Alzheimer’s disease?

Down’s syndrome is a disease that is caused by the trisomy of the 21th chromosome, and is the most frequently occurring chromosome disorder. The symptoms include deformity, developmental disorder, and intellectual disability.
Alzheimer’s disease is the most common form of dementia, and the cause is thought to be the neuronal death by the aggregation of β-Amyloid and tau protein.
In addition, 25 % of the over 35 year old patients of Down’s syndrome develop Alzheimer’s disease, which is five times more frequent than that of people without Down’s syndrome.

The relationship between Down’s syndrome and Alzheimer’s disease

 The genomic region of DYRK1A lies in the critical region of chorosome 21, the cause of Down’s syndrome.
It is reported that there is an up-regulation in the expression of DYRK1A in the brains of the patients of Down’s syndrome.
It is reported that DYRK1A is over-expressed in the brains of patients with Alzheimer’s disease (figure below), and the DYRK1A overexpressing mouse exhibits abnormal formation of the brain and exhibits learning disability and behavioral disorder.
DYRK1A kinase directly phosphorylates TAU protein. Phosphorylated TAU aggregates and leads nerve cell death, causing Alzheimer's disease.

Drugs against central nervous system diseases that Kinopharma aims to develop

 We are developing drugs by targeting the kinase “DYRK1A” that is deeply related to these diseases. We aim to develop unprecedented drugs against central nervous system diseases by targeting DYRK1A.

Current state of development

We have succeeded in developing chemical compounds that specifically inhibit DYRK1A and inhibit the phosphorylation of cellular tau protein. Currently, we are confirming the therapeutic effect in Alzheimer’s disease and Down’s syndrome model animal.

Bibliography

Ogawa, Y., Nonaka, Y., Goto, T., Ohnishi, E., Hiramatsu, T., Kii, I., Yoshida, M., Ikura, T., Onogi, H., Shibuya, H., Hosoya, T., Ito, N., Hagiwara, M., et al. (2010) Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A. Nat Commun 1, 1-9.
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