Schizophrenia is a severe mental health condition linked to the disruption of chemical neurotransmitters affecting cognitive functions. Existing treatments for schizophrenia have limitations primarily due to the challenge of the blood-brain barrier’s selectivity, necessitating the exploration of new approaches.
Schizophrenia is a complex mental illness characterized by various symptoms such as hallucinations, cognitive impairments, and disorganized speech or behavior, attributed to neurotransmission imbalances. Current treatment methods involve antipsychotic drugs that can have side effects and pose a risk of cardiovascular issues. Additionally, drug efficacy is often limited by the blood-brain barrier’s strict control over substance movement into the brain.
To overcome this obstacle and enable the delivery of therapeutic substances to the brain for treating schizophrenia, researchers have investigated receptor-mediated transcytosis (RMT) using low-density lipoprotein receptor-related protein 1 (LRP1). A study led by Associate Professor Eijiro Miyako from Japan Advanced Institute of Science and Technology (JAIST), along with other researchers, published their findings in the JACS Au journal on June 20, 2024.
The researchers were motivated by previous research on vasoactive intestinal peptide receptor 2 (VIPR2) gene duplication in schizophrenia and their own discovery of the peptide KS-133, which acts as a selective antagonist to VIPR2 but faces challenges in crossing the blood-brain barrier. To address this issue, they developed a brain-targeting peptide, KS-487, that binds specifically to LRP1, facilitating RMT. They also created a novel nanoparticle-based drug delivery system (DDS) containing KS-133 and KS-487 for treating schizophrenia.
The administration of the peptide formulations through the DDS effectively delivered the drug to the brains of mice. Pharmacokinetic analysis confirmed the brain-targeting peptide’s role in transporting KS-133 into the brain. Mice treated with KS-133/KS-487 nanoparticles exhibited improved cognitive functions in novel object recognition tests by inhibiting VIPR2 activation.
Dr. Miyako highlighted the potential of their research, stating, “Our peptide formulation could offer a new approach to address cognitive dysfunction in schizophrenia, distinct from current treatments focused on neurotransmitter modulation.” This study provides promising preclinical evidence for a novel therapeutic strategy targeting VIPR2 to alleviate cognitive impairments in schizophrenia.
Looking forward, Dr. Miyako expressed optimism about advancing the research to cell and animal models, and eventually human clinical trials within five years to validate the efficacy and safety of this peptide formulation as a potential new treatment for schizophrenia.
