From nose to brain

Antibodies against specific target molecules or structures in the brain and spinal cord are currently reaching the stage of clinical application for several neurological diseases like Alzheimer’s, Parkinson’s, Multiple Sclerosis, and spinal cord injury. How do they reach the central nervous system, though? The blood-brain barrier blocks easy access through the blood. Therefore, a better way for therapeutic antibodies to reach the central nervous system is urgently needed.

Certain small molecules are known to be able to travel from the nose to the brain. Inspired by this, Martin Schwab and his team applied antibodies – which are large proteins – to the smell mucosa in the nose of rats and mice. The antibodies inactivate the brain protein Nogo-A, thus enhancing the regeneration of injured nerve fibers.

Using biochemical techniques, they detected the antibodies applied to the nose already a few hours later in the brain and the spinal cord of the rats and mice in relevant quantities. When the researchers used the anti-Nogo-A antibodies on rats with large brain damage after stroke, the impaired forelimbs recovered their fine motor abilities. The scientists detected new nerve connections in the brain and spinal cord of treated animals, showing that the antibody had worked there.

Instead of injecting antibodies into the brain, an application route from the nose to the brain would be less risky, less complicated, and also easy to apply at home. Dosage, formulation, and application devices for the specific antibodies and future drugs still need to be worked out.

Reference: Correa D, Scheuber MI, Shan H, Weinmann OW, Baumgartner YA, Harten A, Wahl AS, Skaar KL, Schwab ME (2023). Intranasal delivery of full-length anti-Nogo-A antibody: A potential alternative route for therapeutic antibodies to central nervous system targets. Proc. Natl. Acad. Sci. USA 120 No. 4: e2200057120.

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