Research from the Centre National de la Recherche Scientifique (CNRS) in France indicates that proteins derived from the antibodies of camels and llamas may offer new avenues for treating neurological disorders, including Alzheimer’s disease. These nanoscopic proteins, known as nanobodies, can penetrate cellular spaces more effectively than traditional antibodies, potentially providing a novel approach to combating difficult-to-treat conditions.
According to the CNRS team, nanobodies are significantly smaller than typical antibodies, being about ten times smaller than the common Immunoglobulin G antibody. Given their diminutive size and unique structural properties, they can navigate biological barriers that larger antibodies cannot. These proteins are naturally produced by members of the camelid family, which includes llamas and alpacas, and have been refined in laboratories for therapeutic applications.
Nanobodies have already demonstrated effectiveness in protecting humans from various pathogens, including influenza and COVID-19. Despite this progress, researchers faced significant challenges in utilizing them for brain disorders. Previously, the human body’s kidneys would eliminate these proteins before they could reach their intended targets, particularly across the blood-brain barrier, a critical checkpoint for any drugs designed to act on the brain.
Recent studies have shown promise in overcoming these obstacles. Animal model experiments indicate that engineered nanobodies can traverse the blood-brain barrier and target crucial markers associated with Alzheimer’s, such as tau and amyloid beta. Philippe Rondard, a neuropharmacologist at CNRS, states, “Camelid nanobodies open a new era of biologic therapies for brain disorders and revolutionize our thinking about therapeutics.” He believes these proteins could represent a new class of drugs that bridge the gap between conventional antibodies and small molecules.
Challenges in Development
Despite their potential, significant work remains before these therapies can be safely administered to humans. Researchers must assess the stability and proper folding of the nanobodies to ensure they do not aggregate, which could compromise their effectiveness. Pierre-André Lafon, a functional genomicist, emphasizes that while these proteins are highly soluble and can enter the brain passively, understanding their behavior in the brain is crucial for effective dosage and long-term treatment.
Research teams are currently investigating how these nanobodies cross the blood-brain barrier and how long they persist in brain tissues. Their findings will be essential for developing clinical-grade formulations that can withstand long-term storage and transport, paving the way for eventual patient use.
“Our lab has already started to study these different parameters for a few brain-penetrant nanobodies and has recently shown that conditions of treatment are compatible with chronic treatment,” Lafon adds.
While the prospect of using camel and llama proteins to combat Alzheimer’s is exciting, significant research and development are still necessary. The findings, published in Trends in Pharmacological Sciences, suggest that while we may be far from practical applications, advancements in this area could someday lead to transformative therapies for conditions that currently lack effective treatments.
