Khaberni - Nanobodies made from antibodies in animals such as camels and llamas can penetrate cellular spaces in ways that no other antibodies can.
Increasing evidence suggests that these tiny molecules could be used to protect the brain from difficult-to-treat conditions, such as Alzheimer's and schizophrenia, according to Science Alert based on the journal Trends in Pharmacological Sciences.
A team of scientists at the French National Centre for Scientific Research (CNRS) explained in a new research paper that the small size of the antibodies makes them ideal for accessing and treating the brain with fewer side effects, although the nanobody-based treatments medically approved so far are intended for other parts of the body.
Ultra-precise biological cleaning
Antibodies are proteins used by the immune system to identify viruses, toxins, and others as waste, for the "biological cleaning team" to handle.
Nanobodies are simplified versions of these proteins, having a sleek and precise structure that allows them to sneak between virus defenses and disable their most dangerous parts.
Camels, llamas, and alpacas
The camel family (camels, llamas, and alpacas) produces antibodies that are smaller than their human counterparts. Scientists have been able to refine these antibodies in the lab to be about 10 times smaller than the traditional Y-shaped immunoglobulin G antibody. While sharks are also known for producing nanobodies, mammals closer to humans have biological mechanisms that make them more capable of supporting human immunity.
Nanobodies derived from camels have proven their ability to protect humans from influenza A and B, norovirus causing gastroenteritis, COVID-19, and even the Human Immunodeficiency Virus.
Two major obstacles
Until recently, it was believed that nanobodies were unsuitable for treating brain disorders; because the kidneys accelerate their elimination before they reach their target, in addition to the difficulty of their crossing the blood-brain barrier, a critical checkpoint that prevents most drugs from reaching the central nervous system.
Engineered models that cross the barrier
However, recent studies have overcome these challenges; laboratory experiments on animal models have shown that engineered nanobodies can cross the blood–brain barrier, targeting and removing tau proteins and beta-amyloid associated with Alzheimer's disease.
A new therapeutic era
Philippe Rondard, a specialist in neuropharmacology at CNRS, said, "Nanobodies derived from camels open a new era of biological treatments for brain disorders and revolutionize thinking about therapeutic approaches."
He also confirmed that they could become "a new class of drugs situated between traditional antibodies and small molecules".
Clear benefits and many questions
Meanwhile, Pierre Andre Lafont, a functional genomics scientist, explained that these proteins "are small and highly soluble, and can passively enter the brain". In contrast, small drugs that can penetrate the blood-brain barrier are often hydrophobic, which reduces their bioavailability and increases the likelihood of binding to unintended sites, thereby increasing the risk of side effects.
Lafont also emphasized the need to understand how these proteins cross the blood–brain barrier and how long they stay in the brain to determine the optimal doses. Researchers will also need to develop stable formulations that withstand long-term storage and transportation from the lab to the patient.
He concluded, saying, "Studies have already begun on these factors for some of the nanobodies capable of penetrating the brain, showing that treatment conditions are compatible with chronic use."
