In a development that could transform treatment for neurological diseases, Mount Sinai researchers have engineered a way to deliver messenger RNA (mRNA) directly to the brain through a simple intravenous injection. The breakthrough, published today in Nature Materials, overcomes one of medicine’s most persistent challenges: getting therapeutic molecules past the brain’s protective barrier.
The research team, led by Dr. Yizhou Dong at the Icahn School of Medicine at Mount Sinai, developed specialized lipid nanoparticles that can transport mRNA through the blood-brain barrier – a natural defense system that typically blocks most drugs from reaching the brain. Their successful delivery system could open new possibilities for treating conditions ranging from brain tumors to drug addiction.
“Our study shows that these blood-brain barrier-crossing lipid nanoparticles (BLNPs) can safely and efficiently deliver mRNA into the brain,” says Dong, Professor of Immunology and Immunotherapy at Mount Sinai. “This could open up opportunities to use mRNA-based therapies for a variety of neurological and psychiatric disorders.”
The team’s approach involved creating a library of 72 different lipid molecules specifically designed to cross the blood-brain barrier. Through extensive testing, they identified one formulation, dubbed MK16 BLNP, that showed remarkably higher efficiency than existing FDA-approved delivery systems. The nanoparticles successfully delivered their cargo to neurons and other brain cells, achieving therapeutic effects in multiple disease models.
In experiments with brain cancer, the system effectively delivered tumor-suppressing mRNA to glioblastoma, an aggressive form of brain cancer. When tested in a model of cocaine addiction, the nanoparticles successfully delivered mRNA that altered drug-seeking behavior. The system also worked in tests on human brain tissue samples, suggesting potential for clinical applications.
“Our lipid nanoparticle system represents an important step in the effort to develop mRNA-based treatments for central nervous system disorders,” Dong explains. “The study provides proof of concept that such an approach is viable and could be adapted for a range of diseases where gene therapy or mRNA therapeutics might play a role.”
Dr. Eric J. Nestler, Director of The Friedman Brain Institute at Mount Sinai and co-senior author of the study, emphasizes the broader implications: “Our findings highlight the potential of lipid nanoparticles in overcoming one of the major challenges in treating brain diseases. We are very excited to continue evaluating this novel platform for broader therapeutic applications.”
The development builds on the recent success of mRNA technology in COVID-19 vaccines but takes it in a new direction. While those vaccines primarily target the immune system, this new delivery system aims to influence brain cells directly. The nanoparticles can carry instructions for producing therapeutic proteins directly to brain cells, potentially allowing for more targeted and effective treatments.
The researchers found their system particularly effective at reaching neurons and astrocytes – key brain cell types involved in many neurological disorders. In mouse studies, a single injection could deliver functional mRNA to broad regions of the brain, with effects lasting several days. The system showed minimal toxicity and could be safely administered multiple times.
Before clinical trials can begin, additional safety studies following FDA guidelines will be needed. The researchers also plan to refine the technology to enhance its specificity and efficiency. However, the current results represent a significant advance in the field of brain therapeutics.
The research was supported by the National Institute of General Medical Sciences, the National Institute on Drug Abuse, and Biogen. The findings suggest a promising path forward for treating a wide range of brain disorders that have long proved resistant to conventional therapies.