'Biorchestra' BioOrchestra to conquer Alzheimer's

14 January 2020

[Interview] Ryu Jin-hyeob, CEO, "Performing hope-promising research" Alzheimer's 'fundamental therapy' using RNA

By Lee Won-hee, staff reporter lwh3756@HelloDD.comInput: 2019.11.04 | Modified: 2019.11.06

Alzheimer's is one of the most desperate diseases that humans are experiencing. Unlike physical pain, mental pain is a serious disease in that one forgets the most precious memories one by one. For this reason, various studies have been conducted for the treatment of Alzheimer's disease. But it's true that many research about Alzheimer's was caught on an important threshold.

Even large global pharmaceutical companies are not able to make it easy. A bio company in Daejeon is getting attention by throwing a new ticket. Ryu Jin-hyeob, the CEO of Biorchestra, which is designed to study as if he or she played a single orchestra, is setting the research chord to conquer Alzheimer's.

◆ RNA, the choice for underlying therapies

New drug trends have shifted from cell to cell. Rather than acting on antigens outside of cells like antibodies, they are essentially treating problems within cells. At this time, the material is largely divided into DNA, RNA, and protein, and a biorchestra is developing a therapeutic drug using RNA.

There are two major obstacles to using RNA. The duration of action in the blood and the rate of penetration of the cerebrovascular barrier. "Blood is a harsh environment for external therapeutic substances," said Ryu. "It is difficult to expect a therapeutic effect because normal RNA is degraded around 5 minutes."

"In order to treat a degenerative brain disease called Alzheimer's, we have to cross the cerebrovascular barrier, but it also has an average penetration rate of 0.1 to 0.2 percent of antibodies," he added.

The biorchestra extended the survival time of RNA to about 100 minutes by applying OTV (Oligonucleotide Transport Vehicle). At the same time, small molecules preferred by receptors overexpressed on the surface cerebrovascular barrier were coated to increase penetration.

We also noticed the therapeutic substances in the brain after infiltration. Alzheimer's has abnormalities in β-amyloid and tau protein, leading to memory loss. Existing treatment methods such as Biogen and Lilly used target antibodies to eliminate abnormal aggregate proteins (toxic proteins), but failed as a result.

The biorchestra's chosen direction is 'immune cells'. "It activates the patient's immune cells to remove toxic proteins by themselves," said Ryu. "It is to strengthen the patient's innate immune system, which is different from the existing Alzheimer's treatment direction and has great interest in the pharmaceutical industry." ”He said.

Currently, Denali and Alector are in the early stages of development of therapeutics using immune cells, but there are problems to be solved. TREM2, a protein expressed on the surface of immune cells, is a receptor that recognizes toxic proteins. When the drug is activated to activate the receptor, the phagocytosis is active, and the substances IL-1β and TNFα are generated. These two substances are inflammatory factors that attack normal neurons and cause them to become toxic. In other words, by activating the receptor called TREM2 and at the same time inhibit the immune factor was able to enjoy the optimal therapeutic effect. The Biorchestra took note of this and began to develop new drugs.

Lyu noted the pattern of degenerative brain diseases, including Alzheimer's. "Alzheimer's disease is aggravated by the accumulation of toxic proteins and immune cells," he said. "We've focused on finding therapeutics that don't degrade or replace immune cells."

The solution found by the biorchestra was microRNA. The microRNA has the control effect of two genes: one is a macrophages CD **, like TREM2, and the other is S ****, which inhibits inflammation. The more the microRNA is removed, the more the CD ** and S **** are activated, which activates macrophages and inflammation.

Representative Ryu said, "The experiments in rats showed that toxic proteins disappeared and inflammation did not occur." "OTV penetrating cerebrovascular barrier (OTV) and one microRNA decomposing technology (RNAi) "The regulation of these two genes is at the heart of our treatment, and we're currently at the patent entry stage, especially in the United States."

The idea of ​​biorchestra did not stop here. It has also been applied to other degenerative brain diseases that show the same pattern as Alzheimer's. "Degenerative brain diseases such as Lou Gehrig's disease, Parkinson's disease, and Huntington's disease are also caused by the accumulation of toxic proteins," said Ryu. Was there. "

◆ Players

who were difficult to collect ... Now it's time to play together "It's a research-intensive field, so it was hardest to gather people who could help me. I had to invest half a year in public relations and a year in preclinical strategy.

After completing his Ph.D. in pathological and immune microbiology at the University of Tokyo, Japan, Ryu's choice was a startup. "When I had Alzheimer's patient right in front of me, I wondered what could be the fastest solution," he said. "There were various ways including universities, companies, and research institutes. said.

Since its founding in Tokyo in late 2016, it has built a nest in Korea in April 2017. The biggest difficulty was the workforce problem. There was a lack of high-level researchers and a network for advice. In the meantime, it was the BHA.

Mr. Ryu said, “We have been able to expand our network through BHA, and at the same time, we have been able to understand trends in related fields.” “BHA has now joined Series B, which has led to additional funding.” Told.

Biorchestra's Series B includes BHA, Daily Partners, CKD Changtu, LSK Investment, NHN Investment, E & V Ventures, etc., and Chong Kun Dang Holdings, a holding company of Korea's largest pharmaceutical company, has made a strategic investment of KRW 5 billion. The total attraction is 20 billion won.

"The goal is to license out through continuous technology supplementation and verification," said Ryu. "We are also considering establishing an overseas branch in Boston for this purpose."

"Alzheimer's is a very sad disease. Many pharmaceutical companies, research institutes, universities, etc. are working to solve this problem. Biorchestra will also conduct research that can give hope to many patients."

※ This series was prepared by Daedeok Net and Daejeon Techno Park BIO Convergence Center and appeared in Daejeon BIO Convergence Center Magazine (VOL.1).
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