Roche, Denali und NurExone entdecken neue Wege zur Überwindung der Blut-Hirn-Schranke

The blood-brain barrier constitutes a crucial barrier for drug development: approximately 98% of small molecules and almost all large biological active substances do not reach the brain in sufficient concentration. This limits the effectiveness of potential therapies, particularly for neurological disorders such as Alzheimer’s or spinal cord injuries. Three companies – Roche, Denali Therapeutics and NurExone – are pursuing different approaches to overcome this hurdle: Roche relies on a bispecific antibody technology that circumvents the blood-brain barrier via the transferrin receptor. In an early phase III study, a lead compound reached a PET threshold level for amyloid-beta in 91% of subjects in the 3.6 mg/kg dose group, indicating high penetration – although without proof of clinical benefit. The company is now testing the compound, trontine-mab, in phase III studies, where cognition and daily functioning are critical. Denali Therapeutics likewise uses the transferrin receptor to transport various active substances. In March 2026, AVLAYAH received accelerated FDA approval for the neurological manifestations of the Hunter syndrome in paediatric patients – the first medicinal product in a new class of active substances that specifically use the transferrin receptor for the blood-brain barrier. In its first full-year sales, the product generated US$ 3.6 million net sales. NurExone Biologic is relying on a different strategy: The ExoTherapy platform uses exosomes, natural carrier vesicles derived from mesenchymal stem cells, that are specifically loaded with active substances. The leading candidate, ExoPTEN, is to be used in acute traumatic spinal cord injuries and contains a PTEN-directed siRNA. In a preclinical study published in 2024, labelled ExoPTEN particles were detected in the rat spinal cord several days after injury, demonstrating the ability of the vesicles to deliver the therapeutic agent specifically. However, safety and efficacy in humans have yet to be proven. NurExone plans intrathecal administration, which deviates from systemic access via the blood-brain barrier. While Roche and Denali rely on molecular shuttles that use existing receptors, NurExone combines natural transport mechanisms with local application. The companies are not direct competitors but illustrate how the problem of the blood-brain barrier can be solved in different ways. However, there is still much for NurExone to prove: reproducible production and loading of exosomes, targeted delivery of the active substance, and safety and efficacy in clinical trials. Denali has already demonstrated that transport technologies can become relevant for regulation; Roche demonstrates the need for clinical depth. NurExone is still at the beginning of this proof.