Tiny proteins from camels, llamas, and alpacas—known as nanobodies—may transform treatments for brain disorders like schizophrenia and Alzheimer’s.
Their tiny size allows them to penetrate the brain more effectively and with fewer side effects than conventional antibody therapies.
Tiny Camelid Proteins With Big Potential
Nanobodies, which are tiny proteins found in members of the camelid family such as camels, llamas, and alpacas, may offer a promising new approach for treating brain disorders including schizophrenia and Alzheimer’s disease. According to a study published today (November 5) in the Cell Press journal Trends in Pharmacological Sciences, researchers report that the exceptionally small size of these molecules enables them to target neurological conditions in mice more effectively and with fewer side effects. The study also outlines the steps needed to adapt these treatments for safe use in humans.
“Camelid nanobodies open a new era of biologic therapies for brain disorders and revolutionize our thinking about therapeutics,” says co-corresponding author Philippe Rondard of Centre National de la Recherche Scientifique (CNRS) in Montpellier, France. “We believe they can form a new class of drugs between conventional antibodies and small molecules.”
Discovery of Nanobodies: A Scientific Surprise
Nanobodies were first identified in the early 1990s by Belgian scientists examining the immune systems of camelids. They discovered that, in addition to producing conventional antibodies composed of two heavy and two light chains, camelids also generate a unique type of antibody made solely of heavy chains. The active, antigen-binding portion of these antibodies—now known as nanobodies—is about one-tenth the size of a typical antibody. While similar molecules have been seen in some cartilaginous fish, they have not been found in any other mammals.
The Challenge With Current Antibody Treatments
Many treatments for conditions such as cancer and autoimmune diseases rely on antibody-based drugs, but these have shown only limited success against brain disorders. Even the therapies that do provide some benefit, such as certain Alzheimer’s medications, can cause unwanted side effects.
Because of their much smaller structure, nanobodies could potentially deliver stronger therapeutic effects for brain diseases while reducing these adverse reactions. In earlier studies, researchers demonstrated that nanobodies were able to reverse behavioral problems in mouse models of schizophrenia and other neurological disorders, suggesting a promising path forward for future brain-targeted treatments.
Smarter, Safer, and Easier to Make
“These are highly soluble small proteins that can enter the brain passively,” says co-corresponding author Pierre-André Lafon, also of 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.”
Nanobodies are also easier than conventional antibodies to produce, purify, and engineer and can be fine-tuned to their targets.
From Lab to Clinic: The Road Ahead
The authors acknowledge that several steps need to be taken before nanobodies can be tested in human clinical trials for brain disorders. 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 these molecules stay in the brain—a step that is important for developing dosing strategies.
“Regarding the nanobodies themselves, it is also necessary to evaluate their stability, confirm their proper folding, and ensure the absence of aggregation,” Rondard says. “It will be necessary to obtain clinical-grade nanobodies and stable formulations that maintain activity during long-term storage and transport.”
Steady Progress Toward Human Trials
“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.
Reference: “Nanobodies: a new paradigm for brain disorder therapies” by Pierre-André Lafon, Laurent Prézeau, Jean-Philippe Pin and Philippe Rondard, 5 November 2025, Trends in Pharmacological Sciences.
DOI: 10.1016/j.tips.2025.10.004
This work was supported by the Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, French National Research Agency (ANR-20-CE18-0011; ANR-22-CE18-0003; ANR-25-CE18-0434), Fondation pour la Recherche Médicale (FRM EQU202303016470 and FRM PMT202407019488), LabEX MAbImprove (ANR-10-LABX-5301), Proof-of-concept Région Occitanie and the transfer of Technology Agency SaTT AxLR Occitanie.
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