Researchers at the Icahn School of Medicine at Mount Sinai have developed an innovative approach-;demonstrated in mouse models and isolated human brain tissue-;to safely and effectively deliver therapeutics into the brain, providing new possibilities for treating a wide range of neurological and psychiatric diseases.
Published in the November 25 online issue of Nature Biotechnology [https://doi.org/10.1038/s41587-024-02487-7], the study introduces a first-of-its-kind blood-brain barrier-crossing conjugate (BCC) system, designed to overcome the protective barrier that typically blocks large biomolecules from reaching the central nervous system (CNS).
The blood-brain barrier is a natural protective shield that prevents harmful substances from entering the brain. However, it also blocks the delivery of life-saving drugs, creating a significant challenge in treating conditions like amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, addiction, and many other CNS disorders.
The BCC platform takes advantage of a specialized biological process called γ-secretase-mediated transcytosis to deliver large therapeutic molecules, like oligonucleotides and proteins, directly into the brain through a simple intravenous injection.
The blood-brain barrier is an essential defense mechanism, but it also presents a significant challenge for delivering drugs to the brain. Our BCC platform breaks this barrier, allowing biomacromolecules, including oligonucleotides, to reach the CNS safely and efficiently.”
Yizhou Dong, PhD, co-corresponding senior author, Professor of Immunology and Immunotherapy, and a member of the Icahn Genomics Institute and the Marc and Jennifer Lipschultz Precision Immunology Institute, at Icahn Mount Sinai
The study showed that when the researchers injected a compound called BCC10 linked to specialized genetic tools known as antisense