A Cell Press review published on November 5, 2025, highlights tiny camelid-derived antibodies known as nanobodies as potential tools for treating conditions such as Alzheimer’s disease and schizophrenia. The authors say these proteins can reach brain targets in mice more readily than conventional antibodies and outline key steps before human testing.
Nanobodies—single-domain fragments derived from the heavy-chain–only antibodies found in camels, llamas, and alpacas—are drawing attention as candidates for brain therapies. Identified by Belgian scientists in the early 1990s, these molecules are roughly one-tenth the size of conventional antibodies and have also been observed in some cartilaginous fish.
In a review in Trends in Pharmacological Sciences (published November 5, 2025), researchers from CNRS and the University of Montpellier argue that nanobodies’ compact, highly soluble structure can help them reach targets in the brain more efficiently than traditional antibody drugs. They contend that, in mice, this approach could deliver efficacy with fewer off‑target effects than hydrophobic small‑molecule drugs. “Camelid nanobodies open a new era of biologic therapies for brain disorders,” said co‑corresponding author Philippe Rondard of CNRS. Co‑corresponding author Pierre‑André Lafon added that these proteins “can enter the brain passively,” a claim the team bases on animal studies.
What prior studies show
Evidence in animals underpins the review’s optimism. A CNRS‑led study published in Nature on July 23, 2025, reported that a peripherally injected, engineered bivalent nanobody reached the brain and corrected cognitive deficits in two mouse models characterized by NMDA receptor hypofunction—an experimental framework relevant to aspects of schizophrenia. The authors of the new review also note prior work in mice suggesting nanobodies can restore behavioral deficits in schizophrenia models and other neurological conditions.
Next steps toward human testing
The review outlines requirements before clinical trials: comprehensive toxicology, long‑term safety assessments, and studies of pharmacokinetics and pharmacodynamics to determine how long nanobodies persist in the brain to guide dosing. The authors also call for evaluations of protein stability, proper folding, and the absence of aggregation, along with clinical‑grade manufacturing and stable formulations for storage and transport. According to the team, early lab work has begun to examine these parameters for several brain‑penetrant nanobodies and indicates conditions compatible with chronic treatment—still in preclinical settings.
Production and engineering advantages
Beyond their potential to reach brain targets, nanobodies are generally simpler to produce and purify than full‑length antibodies and can be engineered to bind precisely to chosen receptors. The authors argue this flexibility could position nanobodies as a new class of biologic therapy that sits between conventional antibodies and small molecules for neurological diseases.
Funding for the work summarized in the review was provided by French institutions including CNRS, INSERM, the University of Montpellier, the French National Research Agency, the Fondation pour la Recherche Médicale, LabEX MAbImprove, the Région Occitanie, and the technology transfer agency SATT AxLR.
