Summary: Scientists have developed a fat particle system that enables mRNA to traverse the blood-brain hurdle, a long-standing problem in biology. These nanoparticles safely delivered healing mRNA in studies using mice and people brain cells, opening the door to possible treatments for neurological disorders like Alzheimer’s, ALS, and brain cancer.
This system breaks down barriers safely and effectively using organic transport systems, as opposed to traditional drug supply techniques. The leading development, MK16 BLNP, showed better mRNA supply compared to FDA-approved fat particles.
Important Information:
- Breakthrough Delivery System: Newly designed lipid nanoparticles ( BLNPs ) enable mRNA to bypass the blood-brain barrier, overcoming a major hurdle in treating brain disorders.
- Prospective for Multiple Diseases: The program may be adapted for neurological disorders, psychiatric disorders, and brain tumors by instructing brain cells to produce medical protein.
- Better Performance: The MK16 BLNP development demonstrated substantially higher mRNA supply performance compared to existing FDA-approved nanoparticles.
Origin: Mount Sinai Hospital
A challenge that has long been constrained by the protective nature of the blood-brain barrier has been solved by researchers at Mount Sinai’s Icahn School of Medicine by developing a lipid nanoparticle system capable of delivering messenger RNA ( mRNA ) to the brain via intravenous injection.
The results, in mouse designs and isolated people brain cells, were published in the February 17 website topic of , Nature Elements.
They demonstrate the potential of this technology to pave the way for potential solutions for a wide range of problems such as Alzheimer’s disease, amyotrophic lateral sclerosis, brain tumor, and drug dependency.  ,
The blood-brain challenge serves as a protective helmet, preventing some substances—including potentially useful therapies—from reaching the mind. While earlier studies at Mount Sinai  focused on a different method: using specially designed lipid nanoparticles to carry mRNA across the roadblock. This review focuses on a new approach.
By replacing missing proteins, reducing harmful ones, or activating the body’s defenses, researchers could instruct brain cells to produce therapeutic proteins that can help treat or prevent disease.
” Our study shows that these blood-brain barrier-crossing lipid nanoparticles ( BLNPs ) can safely and efficiently deliver mRNA into the brain”, says co-corresponding senior author , Yizhou Dong, PhD, Professor of Immunology and Immunotherapy, and a member of the Icahn Genomics Institute and the Marc and Jennifer Lipschultz Precision Immunology Institute, at the Icahn School of Medicine at Mount Sinai.
This may lead to the development of mRNA-based treatments for a range of neurological and psychiatric disorders.
To maximize their ability to cross the blood-brain barrier, the research team created and tested a library of lipids. They discovered a lead formulation, known as MK16 BLNP, through a series of structural and functional analyses, that had significantly higher mRNA delivery efficiency than other existing lipid nanoparticles that had been approved by the Food and Drug Administration ( FDA ) ( FDA ).
This system takes advantage of natural transport mechanisms within the blood-brain barrier, including caveolae- and γ-secretase-mediated transcytosis, to move nanoparticles across the barrier, say the investigators.
The BLNP platform successfully delivered therapeutic mRNAs to the brain, showing its potential for clinical use in studies using mouse disease models.
According to Dr. Dong,” Our lipid nanoparticle system is a significant step in the development of mRNA-based treatments for central nervous system disorders.”
The study provides “provedance of concept” for a range of diseases in which gene therapy or mRNA therapies might be effective.
The researchers point out that additional studies, including toxicology studies, are necessary to evaluate long-term safety and efficacy in accordance with FDA recommendations. Future research will concentrate on developing the technology for clinical translation.
According to co-corresponding senior author Eric J. Nestler, MD, PhD, Director of The Friedman Brain Institute, Dean for Academic Affairs, Nash Family Professor in the Nash Family Department of Neuroscience at the Icahn School of Medicine at Mount Sinai, and Chief Scientific Officer of the Mount Sinai Health System,” Our findings highlight the potential of lipid nanoparticles in overcoming one of the major challenges in treating brain diseases.”
” We are very excited to keep evaluating this novel platform for wider therapeutic applications.”
The paper is titled” Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system”.
The study’s authors, as listed in the journal, are Chang Wang, Yonger Xue, Tamara Markovic, Haoyuan Li, Siyu Wang, Yichen Zhong, Shi Du, Yuebao Zhang, Xucheng Hou, Yang Yu, Zhengwei Liu, Meng Tian, Diana D. Kang, Leiming Wang, Kaiyuan Guo, Dinglingge Cao, Jingyue Yan, Binbin Deng, David W. McComb, Ramon E. Parsons, Angelica M. Minier-Toribio, Leanne M. Holt, Jiayi Pan, Alice Hashemi, Brian H. Kopell, Alexander W. Charney, Eric J. Nestler, Paul C. Peng and Yizhou Dong.
Funding: The study was supported by the National Institute of General Medical Sciences ( R35GM144117 ), the National Institute on Drug Abuse ( P01DA047233 ), and Biogen.
About this news about neuroscience and nanotechnology research
Author: Karin Eskenazi
Source: Mount Sinai Hospital
Contact: Karin Eskenazi – Mount Sinai Hospital
Image: The image is credited to Neuroscience News
Original Research: Closed access.
” Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system” by Yizhou Dong et al. Nature Materials
Abstract
Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system
Because they must cross the blood–brain barrier ( BBB ) before entering the brain, the systemic delivery of mRNA molecules to the central nervous system is challenging.
We use these to create BBB-crossing lipid nanoparticles for mRNA delivery. We here design and synthesize 72 BBB-crossing lipids made by combining BBB-crossing modules and amino lipids.
A lead formulation with significantly higher mRNA delivery efficiency than those exhibited by FDA-approved lipid nanoparticles was the result of screening and structure optimization studies.
After being well tolerated across a number of dosage regimens, studies in different mouse models demonstrate that these BBB-crossing lipid nanoparticles can transfect neurons and astrocytes of the entire brain. Moreover, these nanoparticles can deliver mRNA to human brain ex vivo samples.
Overall, these broad-brain regions ‘ BBB-crossing lipid nanoparticles deliver mRNA to neurons and astrocytes, making them a promising treatment for a variety of central nervous system conditions.
