Roche, Denali y NurExone exploran nuevas formas de superar la barrera entre sangre y cerebro

The Blood-brain barrier represents a central barrier to drug development: approximately 98% of small molecules and almost all large biological active substances do not enter the brain in sufficient concentrations. This limits the effectiveness of potential therapies, especially 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 relies on a bispecific antibody technology that uses the transferrin receptor to cross the blood-brain barrier. In an early phase III study, a candidate drug achieved a PET threshold for amyloid beta in 91% of the subjects in the 3.6 mg/kg dose group, which suggests high penetration – although without clinical proof of efficacy. The company is now testing the drug, Trontinemab, in phase III studies, in which cognition and everyday functions are crucial. Denali Therapeutics also uses the transferrin receptor to transport various active substances. In March 2026, AVLAYAH received accelerated FDA approval for neurological manifestations of the Hunter Syndrome in pediatric patients – the first drug in a new class of drugs that specifically uses the transferrin receptor for the blood-brain barrier. The product generated US$ 3.6 million net sales in its first full year of operation. NurExone Biologic follows a different strategy: the ExoTherapy platform uses exosomes – natural transport vesicles derived from mesenchymal stem cells – that are selectively loaded with active substances. The leading candidate, ExoPTEN, is intended for use in acute traumatic spinal cord injuries and contains an siRNA targeting PTEN. In a preclinical study published in 2024, marked ExoPTEN particles were detected in the rat spinal cord several days after injury, which demonstrates the ability of the vesicles to deliver targeted therapy. However, the safety and efficacy in humans remain unproven. NurExone is planning intrathecal administration, which differs from systemic passage through the blood-brain barrier. While Roche and Denali rely on molecular shuttles that exploit existing receptors, NurExone combines natural transport mechanisms with local administration. The companies are not direct competitors, but illustrate how differently the problem of the blood-brain barrier can be solved. However, there is still much to prove for NurExone: reproducible production and loading of exosomes, targeted drug delivery, and safety and efficacy in clinical trials. Denali has already shown that transport technologies can become regulatively relevant; Roche demonstrates the need for clinical depth. NurExone is still at the beginning of this proof.