Camelid 'Nanobodies' — Tiny Proteins from Camels and Llamas Could Pave the Way to Alzheimer’s Treatments

Camelid nanobodies offer a promising route to brain therapies

Tiny protein molecules taken from the blood of camels, llamas and alpacas — known as nanobodies — could become useful treatments for brain disorders such as Alzheimer’s disease while producing fewer side effects, a new review study reports.

Nanobodies are a naturally occurring antibody variant first identified in the 1990s in members of the camelid family. They are roughly one-tenth the size of conventional antibodies and, so far, have not been observed in other mammal groups.

Why size matters for brain disease

Many existing biologic therapies rely on full-size antibodies, which have proven effective in cancer but less successful for disorders of the central nervous system because they have difficulty crossing the blood-brain barrier. Researchers say nanobodies’ much smaller size and high solubility enable better brain penetration, raising the potential for targeted, brain-directed therapies with reduced off-target effects.

“Camelid nanobodies open a new era of biologic therapies for brain disorders and revolutionise our thinking about therapeutics,” said Philippe Rondard of the Centre National de la Recherche Scientifique (CNRS) in France.

Dr Rondard, an author of the review published in Trends in Pharmacological Sciences, suggests nanobodies could form an intermediate drug class between conventional antibodies and small molecules. Earlier animal studies have also hinted at broader applications: one mouse study reported that nanobodies restored behavioural deficits linked to schizophrenia.

Advantages of nanobodies

• Smaller, highly soluble proteins: Can enter the brain more readily and be less prone to hydrophobic off-target interactions seen with some small-molecule drugs.
• Easier engineering and production: Simpler to produce, purify and modify for precise targeting compared with full-size antibodies.
• Potential for fewer side effects: Improved specificity and reduced non-specific tissue binding are expected to lower adverse effects.

Remaining challenges before human trials

Despite their promise, several important steps remain before nanobodies can advance to human trials for brain disorders:

• Optimising reliable delivery methods to the brain and confirming passive or assisted transport mechanisms.
• Comprehensive safety testing in relevant animal models and eventual human safety studies.
• Biophysical characterisation to ensure stability, correct folding and absence of aggregation.
• Production of clinical-grade nanobodies and development of stable formulations that retain activity during long-term storage and transport.

“It will be necessary to obtain clinical-grade nanobodies and stable formulations that maintain activity during long-term storage and transport,” Dr Rondard said, underscoring the translational steps ahead.

In summary, camelid nanobodies represent a compelling new approach for central nervous system therapeutics, but careful optimisation and rigorous testing are required before they can be evaluated in people.