Scientists crack code that delivers mRNA drugs to the brain

In the development of treatments that can alter neurological diseases, Mount Sinai researchers directly designed a method to deliver messenger RNA (mRNA) directly to the brain through simple intravenous injections. The breakthrough published today in Natural Materials overcomes one of the most persistent challenges in medicine: bringing therapeutic molecules beyond the protection barriers of the brain.

A research team led by Dr. Yizhou Dong of Mount Sinai’s Iwang Medical College has developed specialized lipid nanoparticles that transport mRNA through the blood-brain barrier, a natural defense system that usually prevents most drugs from entering the brain. Their successful delivery system can open up new possibilities for treating diseases ranging from brain tumors to drug addiction.

“Our research shows that these blood-brain barrier lipid nanoparticles (BLNPs) can safely and effectively deliver mRNA to the brain,” said Dong, a professor of immunology and immunotherapy at Mount Sinai. “This can be used based on Therapy of mRNA provides opportunities for a variety of neurological and psychiatric disorders.”

The team’s approach involved creating a specially designed library of 72 different lipid molecules that cross the blood-brain barrier. Through extensive testing, they identified a formula called MK16 BLNP that is more efficient than existing FDA-approved delivery systems. The nanoparticles successfully deliver their cargo to neurons and other brain cells, achieving therapeutic effects in a variety of disease models.

In experiments with brain cancer, the system effectively delivers tumor-suppressed mRNA to glioblastoma, an aggressive brain cancer. When tested in a cocaine addiction model, the nanoparticles successfully delivered mRNA that alters drug behavior. The system also examines tests of human brain tissue samples, suggesting possible clinical applications.

“Our lipid nanoparticle system is an important step in the efforts to develop mRNA-based treatment for central nervous system diseases,” Dong explained. “This study provides a feasible proof of concept that this approach can adapt to a range of gene therapies or Diseases where mRNA therapy may play a role.”

Dr. Eric J. Nestler, director of the Friedman Brain Institute at Mount Sinai, co-training of the study highlights a broader implication: “Our findings highlight lipid nanoparticles The potential to overcome one of the major challenges in treating brain diseases. We are pleased to continue to evaluate this novel platform for a wider range of therapeutic applications.”

The development is based on the latest successful establishment of MRNA technology in the Covid-19-19-19-19 vaccine, but in a new direction. Although these vaccines are primarily targeting the immune system, this new delivery system is designed to directly affect brain cells. Nanoparticles can directly produce therapeutic protein instructions to brain cells, making it possible to carry out more targeted and effective treatments.

The researchers found that their system was particularly effective in contacting neurons and astrocytes—the key brain cell types involved in many neurological diseases. In mouse studies, a single injection could deliver functional mRNA to a wide range of brain regions, and its effects lasted for several days. The system exhibits minimal toxicity and can be safely administered multiple times.

Other safety studies that follow FDA guidelines will be required before starting a clinical trial. The researchers also plan to refine the technology to improve its specificity and efficiency. However, the current results represent a significant advance in the field of brain therapy.

The study was supported by the National Institute of General Medicine, the National Institute of Drug Abuse and Biogen. These findings suggest promising pathways to treat a variety of brain diseases that have long been resistant to conventional therapies.