There is a new strategy for the treatment of fundus neovascular diseases

There is a new strategy for the treatment of fundus neovascular diseases

There is a new strategy for the treatment of fundus neovascular diseases.

The number of patients with fundus neovascular diseases is more than 40 million, and as the population ages, the number of patients is still rising
.

As a patient with fundus neovascular diseases, he has to go to a follow-up visit and inject relevant drugs almost every month, otherwise the damage to his eyesight will seriously affect his life

Recently, a study revealed the close interaction between angiogenesis and inflammation in the development of fundus angiogenesis, and based on this, proposed a new idea of ​​"anti-VEGF-anti-inflammatory" synergistic therapy
.

This research, co-authored by researchers from the Institute of Process Engineering of the Chinese Academy of Sciences, Beijing Chaoyang Hospital Affiliated to Capital Medical University, and the University of Queensland in Australia, can significantly improve the efficiency of treatment and is expected to reduce the troubles of frequent medications for the above-mentioned patients
.

The results were published in "Nature-Biomedical Engineering" recently

Existing methods are inefficient and complicated to operate

Existing methods are inefficient and complicated to operate

With the increase of people’s age, the aggravation of myopia or the development of related metabolic diseases, such as pathological myopia, age-related macular degeneration, diabetic retinopathy and other fundus diseases, some unnecessary blood vessels will be newly formed in the fundus
.

These new blood vessels invade choroidal blood vessels, retinal photoreceptor cell layer and other normal fundus tissues, impairing visual function and, in severe cases, blindness

It has been found that Vascular Endothelial Growth Factor (VEGF) plays an important role in the formation of new blood vessels
.

Therefore, intravitreal injection of VEGF antibody drugs such as conbercept, aflibercept and ranibizumab is the main method for clinical treatment of neovascular diseases

Unfortunately, these drugs are difficult to concentrate on the fundus lesions for a long time, and clinical treatment usually requires injections once a month
.

Even so, its effective rate is only 40%-60%

"This has always been a bottleneck in clinical treatment
.

We want to know what can be done to improve the efficiency of treatment?" Dr.

Tao Yong, the corresponding author of this article and professor of ophthalmology at Beijing Chaoyang Hospital, has been engaged in relevant clinical diagnosis and treatment for many years.
Through the establishment of intraocular fluid clinical sample library and the development of microfluidic intraocular fluid detection methods, it is found that fundus neovascular diseases not only contain high levels of VEGF, but also Moreover, a large number of inflammatory factors such as IL-6, IL-1β, and TNF are enriched, and there is an obvious positive correlation between the two
.

"This suggests that if we can control VEGF while also antagonizing these inflammatory factors, it is possible to improve its therapeutic effect
.

" Tian Ying said

New strategy: "Bind and transport, fight separately"

New strategy: "Bind and transport, fight separately"

The State Key Laboratory of Biochemical Engineering has long been committed to solving engineering scientific problems in the industrialization of biotechnology, and biological formulation engineering is an important research direction of the laboratory
.

In recent years, the laboratory has developed a series of intelligent delivery systems and platforms for vaccines, antibodies, and genetic drugs in response to people's lives and health and major national needs, and has actively promoted the clinical transformation of scientific research results
.

Previous studies have found that exosomes (rEXS) derived from regulatory T cells (Treg) in the body have anti-inflammatory function, but simple injection of it and VEGF antibody (aV) is not ideal
.

"At the same discovery, rEXS can chemotaxis to the corresponding target at the focus, expand antagonistic work, but VEGF antibodies can not accurately reach the appropriate target
.
" Tied for the first author of this paper, the CAS process engineering doctorates by Zhang Fan said, "If the aV with rEXS simple connection, although the agreement reached space, but because the two mutual restraint, can not find their target release, is not conducive to the two co-treatment
.
"
.

Chinese Academy of Sciences

This is like two soldiers who have their own missions.
To facilitate their tying together and sending them to the combat zone, if they are not "unbound" when performing their missions, it will affect their work efficiency
.

After design exploration, the researchers plan to work hard on the "rope
.
" If you get to the "combat zone," the rope used for binding can be automatically cut off.
Isn't it the best of both worlds?

It is found that there are a large number of matrix metalloproteinases (MMP) in the neovascular lesions of the fundus.
Some researchers have designed peptides that can be cleaved by MMP enzymes, namely matrix metalloproteinases (MMP) sensitive peptides (cL).
A large number of applications in the field of tumor neovascularization research
.

"We used cL as the'rope' and created the rEXS-cL-aV system to realize the binding and transportation during injection.
When the MMP enzyme is encountered at the lesion, the cL of the'rope' is automatically lysed
.
" Zhang Fan said
.

Choroidal neovascularization (CNV) animal model experiments in mice and cynomolgus monkeys have proved that a single injection of rEXS-cL-aV can significantly inhibit the occurrence and development of neovascular diseases, and the effect is significantly better than the existing single VEGF antibody treatment methods
.

Multiple adjustments to enhance the therapeutic effect

Multiple adjustments to enhance the therapeutic effect

"Fundus neovascular disease is an important cause of blindness.
Traditional single anti-VEGF therapy still has limitations.
The development of new treatments has important clinical significance
.
Through clever methods to connect exosomes and VEGF antibodies, it can achieve anti-inflammatory and anti-inflammatory effects.
The dual effect of VEGF, realizing the spatial and temporal coupling of treatment, is an innovative research with great practical prospects
.
” commented Xie Lixin, academician of the Chinese Academy of Engineering
.

Wei Wei, the corresponding author of this article and a researcher at the Institute of Process Engineering of the Chinese Academy of Sciences , said that the above results are still animal-level preclinical studies, and the actual clinical efficacy remains to be further studied
.
In view of the safety of autologous cell components and approved antibodies, the effectiveness and reproducibility of treatment results, the preparation has good transformation potential
.

Chinese Academy of Sciences

"In the future, we will continue to develop more new preparations for exosomes, explore new treatments for other eye diseases, improve research before clinical trials, and strive to let patients with eye diseases enjoy this technology as soon as possible
.
" Tao Yong accepted "China Science Daily" said in an interview
.

This work is the team's new breakthrough in the field of fundus disease treatment based on previous research foundations
.
Dr.
Tian Ying and Dr.
Zhang Fan are the co-first authors, and Professor Tao Yong, Researcher Wei Wei, and Professor Yu Di are the co-corresponding authors
.
Related work was supported by the National Natural Science Foundation of China General Program, the Beijing Municipal Education Commission Science and Technology Program and the Beijing Chaoyang Hospital Talent Training Program
.
(Source: China Science News Liu Runan and Zhang Siwei)

Related paper information: http://dx.
doi.
org/10.
1038/s41551-021-00764-3

http://dx.
doi.
org/10.
1038/s41551-021-00764-3