Advancing nose-to-brain delivery, team treats stoke in rodents using intranasal antibody

Researchers have generated more preclinical evidence that intranasal delivery can get antibodies to the brain, presenting data that suggest the administration route can achieve concentrations close to those provided by invasive intrathecal infusions.

Antibodies against targets in the central nervous system, notably the Alzheimer’s disease drugs Aduhelm and Leqembi, are now on the market, but delivery remains a challenge. Given systemically, only a small percentage of the administered antibody gets to its target. Intrathecal infusions bypass the blood-brain barrier and thereby get more of the antibody to the target, but they are invasive.

The search for a noninvasive delivery method suitable for repeat dosing in large indications has led researchers to assess intranasal administration. Through the work, scientists have shown that the nose offers a potential alternative route to the brain.

Writing in PNAS, a team from the University of Zurich describes work to add to the evidence on the route of delivery. The paper discusses intranasal delivery of a mouse monoclonal antibody against Nogo-A, a membrane protein that restricts neuronal plasticity and has therefore been identified as a target for stroke therapy.

The study found full-size antibodies reached the brains and spinal cords of mice and rats after intranasal delivery. Daily dosing for a week resulted in concentrations that approached levels achieved through intrathecal delivery. After two weeks, rats treated with intranasal doses showed significant functional recovery.

Further preclinical work is needed to understand pharmacokinetics, mucosal toxicity and much more. It is unclear, for example, how nasal formulations will affect mucociliary clearance and local pH and immune surveillance.