Curative medicine, Diagnostic products

# Creation of methionine dehydrogenase for homocystinuria diagnosis

## Life Sciences

Keyword: Basic studies on enzyme chemistry, A technology transfer to contribute to our society by putting the basic studies into practice

Organizations Involved

Yasuhisa Asano, Professor, Toyama Prefectural University

○ Mr. Noriyoshi Kishimoto, President, Sapporo Immuno Diagnostic Laboratory Co. Ltd.

President Kishimoto

## 【Abstract】

Toyama Prefectural University has created a new enzyme methionine dehydrogenase, based on the basic studies on the development of new enzymes and their industrial uses, together with the experience of Sapporo Immuno Diagnostics Laboratories (Sapporo IDL), who has been producing several mass-screening kits for diagnosis of inborn errors of metabolism such as phenylketouria (PKU) and other diseases. They have enough know-how on phenylalanine dehydrogenase which has been practically used as a component of the diagnosis kit of PKU for more than 10 years, developed by Prof. Asano.

## 【Summary of the technology transfer】Technological Impact

With the new enzyme, it is possible to determine the concentration of L-methionine in the blood of neonates for the diagnosis of homocystinuria. It has been noticed that the current method tends to have false positive errors. Since the fluorometric detection of L-methionine uses the same chemistry with other enzymatic detection methods for phenylketonuria, maple syrup urine disease, and galactosemia, it would be possible to diagnose the four diseases simultaneously in the future.

## ●Social Impact

The development of the new method of diagnosis of homocystinuria will much contribute to an early treatment of neonates with the disorder, since it would cause mental retardation, dislocation of lens of eye, cataract, skeletal abnormalities, thrombosis, etc, if left uncured. It is expected that the kit will be utilized in the public experimental stations of the local Governments as one of the tools of the mass-screening of neonates for diagnosis of inborn errors of metabolism.

## ●Special Features of the Collaboration

It is expected that an integrated multi-enzyme chip, such as that with functions to diagnose homocystinuria, phenylketonuria, maple syrup urine disease, and galactosemia, will be developed. Production of enzymatic diagnosis kits and enzyme chips will be extended to the development of industries related to biotechnology, electronics, and machineries.

## Project Background

In 1992, Sapporo IDL launched a commercial kit for the diagnosis of PKU using phenylalanine dehydrogenase, discovered by Prof. Asano. Since 2003, the studies on the development of a diagnosis kit of homocystinuria has been started.

## Funding History

Since 2003, Prof. Asano has been funded by the project “Toyama medical bio cluster” (Ministry of Education, Culture, Sports, Science and Technology), coordinated by Toyama New Industry Organization.

## I ntellectual property protection

Four domestic and one PCT patents; Phenylalanine dehydrogenase with altered functions, and the analysis of amino acids in the biological samples with the enzyme (JP 2006-243967).

## A kit for detection of Homocystinuria (an image)

The blood of neonates will be spotted on a paper and dried. The extract from the blood will be analyzed by enzymatic fluorometry.

## The chemistry of L-methionine determination

Resazurin will be reduced with NADH formed by the action of methionine dehydrogenase and diaphorase. Resorufin formed shows fluorescence.

## Turning point in the Project

Both the University and the company have strong wills to put their technologies into practice. There has been a mutual understanding between the University and the company, based on the previous success in the development of the diagnosis kit for PKU.