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Change in animal test heightens possibilities of developing dementia drugs‘Unifies evaluation method for clinical, animal tests,’ says Yonsei professor introducing touchscreen cognitive behavior assessment system
  • By Song Soo-youn
  • Published 2018.12.13 15:28
  • Updated 2018.12.13 16:22
  • comments 0

Startups can succeed in researching and developing new products but often experience difficulties in commercializing them because of fund shortages and other reasons. Industrial experts call such a period “death valley.” Developers of new drugs also undergo the “death valley” – throwing out new development when animal tests do not lead to successful clinical trials.

There are countless cases, in which pharmaceuticals’ efforts to develop new treatments end up as failures, as their hard-found new drug candidates, which show good effects in animal experiments, fail to prove the same efficacy and safety in clinical trials. What if the causes of failure do not lie in the candidate substances but in the method of conducting animal tests, however? Particularly if the cognitive behavior evaluation system is different between animal test and clinical trials as is the case of dementia, there can be limi

Touchscreen-based pre-clinical animal model evaluation system (Credit: Ministry of Health and Welfare)

tations in proving the efficacy of the candidate substances of new drugs.

In animal experiments, researchers usually test how much time lab mice with dementia can save in finding their ways in mazes or water. Sometimes, they jolt mice with electricity to make the animals memorize where specific substances are located.

In the clinical trials of dementia patients, however, researchers do not adopt the same methods applied to animals. Usually, they give 12 words to the patients and assess how many of them are remembered after a specific time. In short, researchers use a completely different method to measure the efficacy of the candidate substances of new dementia drugs between animal tests and clinical trials.

And that explains why the University of Cambridge has developed a touchscreen cognitive behavioral evaluation system. A research team at the U.K. school developed a touchscreen system, in which it can apply various cognitive behavior assessment items used for humans to animal tests, too.

Yonsei University College of Medicine (YUMC) introduced the system in 2016. Professor Kim Eo-su, who was studying at the University of Cambridge took the lead in bringing it to Korea. Professor Kim said he expects the system will play a role in narrowing the gap between animal tests and clinical trials by overcoming the limits of the existing animal experiments. It will also prove to be effective in finding out causes that result in cognitive behavioral disorder, he added.

And the Yonsei professor, along with research teams at the Cambridge University and Kings College London, used this system to find out “TDP-43 (transactive response DNA binding protein 43 kDa, TARDBP) genetic mutation causes brain behavior dysfunction related to frontal lobe dementia or Lou Gehrig’s disease. The study results were published in” Nature Neuroscience” on March 19, a journal with the highest authority in this field.

“Associate memory is important for dementia patients, but researchers do not assess associative memory in animal experiments. In clinical trials, they evaluate simple memory or recall memory by giving 12 words,” Professor Kim said. “Global pharmaceuticals are developing dementia treatments. In many cases, however, the developed therapies show good effects in animal tests but fail to do so in clinical trials. Or researchers might have failed to prove their efficacy properly.

Kim noted that “death valley” occur for various reasons in the course of developing new drugs, adding that one of them is the different evaluation methods between animal tests and clinical trials. He emphasized that the touchscreen cognitive behavioral evaluation system has unified the two different ways.

“Candidate substances that have little effects had better be termed failures -- sooner than later – before they enter into the clinical phase that could require several trillion won, to minimize losses,” Kim said. “By making the use of this system, we can enhance prediction ability in the intermediate phase from basic research to clinical study. In other words, we can predict more precisely whether and how much the results of animal tests could be repeatedly shown in clinical trials.”

Professor Kim Eo-soo of Yonsei University College of Medicine explains about touchscreen cognitive behavior assessment system, during an interview with Korea Biomedical Review at the Severance Hospital on Monday.

Unlike in the existing animal tests, this system can also carry out a multi-area evaluation, such as cognitive flexibility and attention concentration, Professor Kim said. Furthermore, researchers can assess dementia-related behavioral disorder and grasp which part of the brain causes specific conduct disturbance, he explained, adding that clinical translational researches are possible.

He also expected touchscreen cognitive behavioral evaluation system could change the trend of animal experiments.

“Many researchers do not believe the existing animal tests at all, because results could vary depending on circumstances,” Kim said. “As there were few alternatives, researchers had conducted tests according to conventional methods, but the introduction of this system will be able to narrow the gap.”

He went on to say, “Given the recent trends, it will likely be meaningless if researchers try to prove study results in brain science area using the existing animal tests.”

Yonsei University College of Medicine is operating three units of touchscreen cognitive behavioral evaluation system. Each system can test four mice at the same time. YUMC is using this system to assess candidate substances of new dementia treatments.

soo331@docdocdoc.co.kr

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