Breakthrough Method Delivers Therapeutics Across Blood-Brain Barrier: Promising Advances in Neurological Treatments
Researchers at the Icahn School of Medicine at Mount Sinai have developed a new method to help deliver large therapeutic molecules into the brain. This breakthrough addresses a major challenge in treating brain diseases: getting drugs past the blood-brain barrier (BBB). Their study, published in Nature Biotechnology, shows that this new platform could lead to effective treatments for diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and various forms of addiction.
The blood-brain barrier acts as a protective filter, preventing harmful substances from entering the brain but also blocking many beneficial drugs. The Mount Sinai team created a blood-brain barrier-crossing conjugate (BCC) platform that allows large molecules like proteins and oligonucleotides to reach the brain.
This platform uses a biological process called γ-secretase-mediated transcytosis. By connecting antisense oligonucleotides to a compound named BCC10, researchers successfully delivered these molecules through an intravenous injection. In tests with mouse models and human brain tissue, the method silenced harmful genes linked to neurological disorders.
Dr. Yizhou Dong, a senior author of the study, stated that their BCC platform enables safe and efficient delivery of biomacromolecules to the central nervous system. In their experiments, the researchers injected antisense oligonucleotides linked to BCC10 into mice, showing significant reductions in gene activity related to ALS and Alzheimer’s disease. For example, they reduced the expression of the Sod1 gene, which is associated with motor neuron degeneration in ALS. They also targeted the tau protein gene MAPT to tackle Alzheimer’s.
Dr. Eric J. Nestler emphasized the potential of this platform to improve treatments for a wide range of brain diseases. The BCC system showed good safety in mice, with minimal impact on major organs. Next, the researchers plan to test their method in larger animal models to further explore its therapeutic potential.