Tiny protein molecules derived from the blood of llamas and camels could be useful in treating brain disorders such as Alzheimer’s disease with fewer side effects, a new study says.
These nanobodies are a form of the immune system’s antibodies, and were first discovered in the 1990s in the camelid family, which includes camels, llamas, and alpacas.
They are about one-tenth the size of conventional antibodies and have not been found in any other mammals.
While current treatment approaches for diseases like cancer often centre around antibodies, these therapies have had limited effect in treating brain disorders, as the antibody molecules struggle to cross the body’s natural blood-brain barrier.
But due to their much smaller size, nanobodies have the potential to be developed into more effective treatments for brain diseases with fewer side effects, researchers say.
“Camelid nanobodies open a new era of biologic therapies for brain disorders and revolutionise our thinking about therapeutics,” said Philippe Rondard of Centre National de la Recherche Scientifique (CNRS) in France.
“We believe they can form a new class of drugs between conventional antibodies and small molecules,” said Dr Rondard, an author of the new study published in the journal Trends in Pharmacological Sciences.
A previous study also showed in mice that nanobodies can restore behavioural deficits of schizophrenia.
“These are highly soluble small proteins that can enter the brain passively,” said Pierre-André Lafon from CNRS.
“By contrast, small-molecule drugs that are designed to cross the blood-brain barrier are hydrophobic in nature, which limits their bioavailability, increases the risk of off-target binding, and is linked to side effects,” explained Dr Lafon, another author of the study.
Nanobodies are also easier to produce, purify, and engineer and can be fine-tuned to their targets compared to conventional antibodies, scientists say.
However, several steps are needed before nanobodies can be tested in human clinical trials for brain disorders, they say.
Mainly, optimising the delivery of nanobodies and ensuring their safety are major challenges, according to scientists.
“Regarding the nanobodies themselves, it is also necessary to evaluate their stability, confirm their proper folding, and ensure the absence of aggregation,” said Dr Rondard.
“It will be necessary to obtain clinical-grade nanobodies and stable formulations that maintain activity during long-term storage and transport,” he said.