Brain Science Research: Humans’ Challenge to the “Ultimate Frontier” of Natural Science

In 2021, the Lasker Prize, one of the most prestigious international biomedical awards, was awarded to three scholars in the field of optogenetics: Peter Hegemann, Karl Deisseroth and Dieter Oesterhelt

They discovered the basic mechanism of microbial channels that convert photons into ion currents, and thus opened up the exploration of brain cell functions, and then tried to unlock the mysteries of neurology, psychiatry and other medical sciences, and once again attracted the public's vision to nature The "ultimate frontier" of science-brain science

The development process of brain science and its basic research

The human brain is a very complex and sophisticated organ, with a complex neural network composed of at least 100 billion neurons connected to each other

In recent years, in order to take the lead in the field of brain science, the United States, Japan, China and other countries have successively launched government-led brain science research programs, which have greatly promoted the development of this field

Figure: The publication of papers and patent applications in the field of brain science in major countries from 2016 to 2020

The development of brain science is inseparable from the iterative upgrade of brain imaging technology

Early brain imaging research methods mainly used optical microscopy technology combined with chemical staining to detect and observe brain morphology and function

In the early 1990s, functional magnetic resonance imaging technology was born and widely used in the field of neuroscience

Figure: 3D magnetic resonance imaging scan of the human brain after artificial staining

Source: KH Fung/Science Photo Library

In recent years, with the addition of new technologies such as genetic technology, genetics technology, and nanotechnology, brain science has developed explosively.

Figure: Integrated neurophotonics technology based on photonic neural probe array

In October 2020, researchers from the California Institute of Technology published a new technology called "Integrated Neurophotonics" in Neuron

At present, the development of brain science has entered a specific application stage.

Application of the development of brain science in brain diseases

At present, brain-related diseases, including various neurological and mental diseases, have surpassed cardiovascular diseases and cancer as the greatest threat to human health

Optogenetics technology and eye diseases

Combining Optics and Genetics optogenetics technology can effectively control the activity of specific types of neurons in the brain, spinal cord, and peripheral nerves of living animals and even free-moving animals

Figure: Optogenetics technology

In April 2020, the French biological company GenSight Biologics, which focuses on innovative gene therapy for neurodegenerative retinal diseases and central nervous system diseases, announced that its PIONEER GS030 Phase I/II clinical trial based on optogenetics and gene therapy is accepting DSMB (Independent Data Security Board) second planned security review

GS030 is a new type of optogenetics technology platform developed based on GenSight technology.

Currently, GS030 is awarded the title of "Orphan Drug" in the United States and Europe

Tau-PET brain imaging technology and Alzheimer's disease

Alzheimer's disease (AD) is the leading cause of dementia, and it has quickly become one of the most burdensome diseases in this century

It has two main symptoms: one is senile plaques formed by abnormal deposition of β-amyloid outside of neuronal cells, and the other is NFTs (neuronal fibrillary tangles) formed by abnormal phosphorylation of tau protein
.
Many elderly people with amyloid deposits in the brain have no symptoms of dementia, but NFTs have been shown to be related to symptoms such as memory loss and confusion
.

Scientists recognize that tau is more directly responsible for brain degeneration in Alzheimer’s disease than amyloid, and also confirmed that the recently developed tau-based PET (positron emission tomography) brain imaging technology (tau-PET) can be Accelerate clinical trials for Alzheimer's disease and improve personalized patient treatment
.
For example, in May 2020, the Tau protein tracer fluroxypyr F18 was approved by the FDA and began to be used in clinical practice
.

Figure 5 Aβ and Tau mechanism

With the development of brain science, the ability to diagnose and treat AD has also been effectively improved, especially in the field of biomarkers.
At present, the three most effective neuroimaging biomarkers are the medial temporal lobe atrophy shown by MRI.
, Posterior cingulate gyrus and temporal parietal hypometabolism shown by FDG-PET, and Aβ deposition shown by amyloid PET imaging
.
Amyloid PET is the most useful in excluding AD, and FDG-PET is the most valuable for the diagnosis of neurodegenerative diseases, predicting short-term clinical results, and determining the course of neurodegenerative diseases
.
The credibility of the three neuroimaging markers has been confirmed, but the clinical validity remains to be verified
.
Future prospective studies need to explore the clinical application and validity of Aβ imaging
.

Neuronal transcription and epilepsy

Epilepsy (Epilepsy) is a chronic neurological brain disease that affects more than 68 million people worldwide
.
Active epilepsy is a devastating disease.
Patients need continuous care, which brings physical, psychological and social burdens to patients and their families
.
The number of new epilepsy patients in China is increasing year by year, among which children account for the largest proportion.
It is a clinical syndrome characterized by highly synchronized discharges of neurons in local lesions in the brain
.
If the activity of the temporal lobe area of ​​the brain of a severe epilepsy patient is inhibited, it will also lose the ability to learn new knowledge, which makes the drug treatment of temporal lobe epilepsy very difficult
.

Figure 6 Based on comprehensive analysis of neuron subtypes most vulnerable to epilepsy

In order to determine the dysfunctional neuronal subtypes associated with epileptic seizures in the human brain, in October 2020, researchers at the University of Copenhagen, Denmark, conducted a mononuclear transcriptomic analysis of 117,000 neuronal transcriptomes to determine epileptic cortical transcription Large-scale changes in multiple neuron subtypes were distributed in the group, and the neuron most affected by epilepsy was found
.
Studies have also found that glutamate signaling is one of the most serious signals of epilepsy disorders
.

In addition, in December 2020, researchers from the Glaston Institute in the United States found that the continuous and rapid monitoring effect of microglia can help prevent the brain from epileptic activity caused by excessive excitability, which may be Alzheimer’s disease and epilepsy.
Many neurological diseases, including autism, open up new treatment avenues
.

The layout of domestic enterprises in the field of brain science

At present, China has formed three main types of research subjects in the field of brain science
.
The first is the North and South centers of the China Brain Project (Shanghai Brain Science and Brain-like Research Center, Beijing Brain Science and Brain-like Research Center); the second is the Frontier Science Center of Brain Science, Fudan University, and the Frontier Science Center of Brain and Brain-Computer Fusion of Zhejiang University Represented by the Frontier Science Center of the Ministry of Education; the third is a variety of research institutions established by domestic universities and research institutes, such as Tsinghua University, Peking University, Beijing Normal University, the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences and the McGovern Brain Academy of Sciences
.

According to public reports and statistics, the relevant layout companies are as follows.
Most of them are start-up technology companies, and there are also leading companies in the industry such as Ali.
The products focus on health monitoring and diagnosis and treatment of epilepsy and brain diseases
.

The brain science layout companies currently in a leading position in China should not be able to bypass You Nao Yinhe
.

Younao Galaxy completed an angel round financing of 42 million yuan led by Fengrui Capital in September 2019, and completed a 500 million yuan A round of financing on August 30, 2021.
The reason why it has attracted much attention is that Younao Galaxy The world’s only "Precision Brain Platform for Individuals", for the first time on an individual clinical level, can help doctors observe human brain functions and connections on the scale of neural function circuits
.

Figure: There are obvious differences in the precise brain function areas of individual humans

This technology is called "POINT Therapeutics", which uses a non-invasive "brain-computer-computer-brain" interaction method to "read signals, decode signals, and write signals" on the human brain to perform precise detection and analysis at the individual level.
Diagnose, and realize precise intervention of brain diseases under the guidance of personalized brain function areas
.
Previously, Professor Liu Hesheng's team used the method of individual brain function network analysis for schizophrenia and obsessive-compulsive disorder symptom analysis, and published related papers in multiple journals
.
At present, You Nao Yinhe is conducting clinical diagnosis and treatment trials with many top hospitals in China for depression, Alzheimer's disease, Parkinson's disease, autism, post-stroke aphasia and other serious brain diseases
.
Hope to make a breakthrough soon
.

It is also worth mentioning that hospitals are gradually playing a more important role in the field of brain science
.
On September 28, 2021, Xuanwu Hospital of Capital Medical University announced the signing of a strategic cooperation agreement with United Imaging Medical and the establishment of the Xuanwu-United Imaging Brain Function and Molecular Imaging Joint Laboratory to focus on major neurological diseases and prospective research in brain science.
A world-class brain science innovation center
.
Based on this cooperation, Xuanwu Hospital and United Imaging will jointly create a brain function and molecular imaging joint laboratory to promote chip-level source innovation and full-chain linkage innovation
.
Close cooperation is carried out on early diagnosis, precise treatment, efficacy follow-up, drug development and efficacy evaluation of neurological and senile diseases
.

summary

At present, brain science research has entered a critical period of development.
Countries are seizing the commanding heights of brain science.
The development momentum of brain science is rapid and continuous breakthroughs.
However, the challenges behind prosperity cannot be ignored
.
It is hoped that a group of innovative companies in China will be able to squeeze the young phoenix into the voice of the old phoenix, and strive for the first in the "ultimate territory"-the field of brain science
.

Note: The original text has been deleted

references

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1038/d41586-019-00677-x.

[3] doi: 10.
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[4] Karl Deisseroth, et al.
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[5] Lancet.
2021 Mar 2: S0140-6736(20)32205-4.

[6] DOI: 10.
1038/s41467-020-18752-7.

[7] "2021 Global Brain Science Development Report" China Institute of Electronics, Zhongcheng Think Tank Consulting (Beijing) Co.
, Ltd.
, Fuxi Jiuzhen Intelligent Technology (Beijing) Co.
, Ltd.
All rights reserved

[8] You Nao Yinhe, United Imaging Medical's official website