Roche, Denali et NurExone découvrent de nouvelles voies pour franchir la barrière hémato-encéphalique

The blood-brain barrier represents a major barrier for drug development: around 98% of small molecules and almost all large biological active substances do not reach the brain in sufficient concentrations. This limits the effectiveness of potential therapies, particularly in neurological diseases such as Alzheimer’s or spinal cord injuries. Three companies – Roche, Denali Therapeutics and NurExone – are pursuing different approaches to overcome this hurdle: Roche is relying on a bispecific antibody technology that crosses the blood-brain barrier via the transferrin receptor. In an early Phase-III study, a drug candidate achieved an amyloid-beta PET threshold of 91% of the participants in the 3.6 mg/kg dose group, which suggests high penetration – although still without any clinical evidence of benefit. The company is now testing the drug, Trontinemab, in Phase-III studies in which cognition and daily function are crucial. Denali Therapeutics also uses the transferrin receptor to transport various drugs. In March 2026, AVLAYAH received expedited FDA approval for neurological manifestations of Hunter syndrome in paediatric patients – the first drug in a new class of drugs targeting the transferrin receptor for the blood-brain barrier. In its first full-year revenue, the product generated $3.6 million in net sales. NurExone Biologic is relying on a different strategy: the ExoTherapy platform uses exosomes – natural transport vesicles derived from mesenchymal stem cells – which are targeted using active substances. The leading candidate, ExoPTEN, is intended for use in acute traumatic spinal cord injuries and contains a siRNA targeting PTEN. In a preclinical study published in 2024, labelled ExoPTEN particles were detected in the spinal cord several days after injury in rats, demonstrating the vesicles’ ability to deliver targeted therapy. However, safety and efficacy in humans remain unproven. NurExone plans intrathecal administration, which is distinct from systemic passage through the blood-brain barrier. While Roche and Denali rely on molecular shuttles that utilise existing receptors, NurExone combines natural transport mechanisms with local administration. The three companies are not direct competitors but illustrate how the problem of the blood-brain barrier can be solved in different ways. For NurExone, however, there is still much to prove: reproducible production and loading of exosomes, targeted release of active substances, and safety and efficacy in clinical trials. Denali has already shown that transport technologies can be of regulatory relevance; Roche demonstrates the need for clinical depth. NurExone is still in the process of proving this.