Chemicals from camels and alpacas used to treat human brain disorders

Tiny, antibody-like proteins - called nanobodies - from animals in the camelid family, such as alpacas and llamas, could play a key role in treating conditions including schizophrenia, say scientists.

They explained that nanobodies’ small size allows them to treat neurological conditions more effectively and with fewer side effects in mice.

The study, published in the journal Trends in Pharmacological Sciences, outlines the next steps towards developing nanobody treatments that are safe for humans.

Study co-author Dr. Philippe Rondard, of Centre National de la Recherche Scientifique (CNRS) in France, said: "Camelid nanobodies open a new era of biologic therapies for brain disorders and revolutionise our thinking about therapeutics.

“We believe they can form a new class of drugs between conventional antibodies and small molecules.”

Nanobodies were first discovered in the early 1990s by Belgian scientists studying the immune systems of camelids.

They found that, as well as making conventional antibodies, which are composed of two heavy chains and two light chains, camelids also produce antibodies with just heavy chains.

The antigen-binding fragments of those antibodies - now known as nanobodies - are one-tenth the size of conventional antibodies.

They have not been found in any other mammals, say scientists, although they have been observed in some cartilaginous fish.

Therapeutic approaches for diseases such as cancer and autoimmune disorders often centre around antibodies.

But, until now, antibody therapies have had limited effect in treating brain disorders.

The treatments that have shown some therapeutic benefits, including a few drugs for Alzheimer’s treatment, are often associated with secondary side effects.

But, with their much smaller size, scientists say nanobodies have the potential to offer better efficacy for brain diseases with fewer side effects.

In previous studies, the team has shown that nanobodies can restore behavioural deficits in mouse models of schizophrenia and other neurologic conditions.

Co-author Dr. Pierre-André Lafon, also of CNRS, said: “These are highly soluble small proteins that can enter the brain passively.

“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.”

He says nanobodies are also easier than conventional antibodies to produce, purify, and engineer and can be fine-tuned to their targets.

But the researchers acknowledge that several steps need to be taken before nanobodies can be tested in human clinical trials for brain disorders.

They say toxicology and long-term safety testing are essential, and the effect of chronic administration needs to be understood.

Pharmacokinetics and pharmacodynamics will also need to be studied to determine how long the molecules stay in the brain - a step that is important for developing dosing strategies.

Dr. Rondard said: “Regarding the nanobodies themselves, it is also necessary to evaluate their stability, confirm their proper folding, and ensure the absence of aggregation.

“It will be necessary to obtain clinical-grade nanobodies and stable formulations that maintain activity during long-term storage and transport.”

Dr. Lafon added: “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."