Bradykinin

EMA's CHMP recommended garadacimab for HAE, ages 12+, as a once-monthly preventive treatment. The European Commission will review the recommendation, with a decision expected in Q1 2025. Garadacimab, designed to block FXII activation, reduced swelling attack rates by over 85% in a Phase 3 trial, with ongoing extension study showing 95% reduction and half of patients free from attacks. Common side effects were injection site reactions.

A Phase 2 clinical trial of gene-editing therapy NTLA-2002 showed that 50 mg doses led to an 80% reduction in swelling attacks over 16 weeks, with 8 out of 11 patients free from attacks. The 25 mg dose also showed positive results, with 40% of patients experiencing no attacks. Intellia Therapeutics, the developer, plans to advance the 50 mg dose to Phase 3 trials.

Hereditary angioedema (HAE) treatment options have expanded with eight FDA-approved medications and more in development. HAE, a rare genetic disorder, involves C1 esterase inhibitor gene mutations causing severe swelling. While no cure exists, therapies like kallikrein inhibitors (Lanadelumab-flyo, Berotralstat, Ecallantide) and C1 esterase inhibitors (Cinryze, Haegarda, Ruconest, Berinert) aim to prevent and manage attacks.

Strategies to enhance drug transport across the BBB include temporary disruption via physical/chemical means, targeting endogenous transporters, and using bradykinin or claudin-5 for permeability. FUS technology offers targeted, non-invasive BBB opening with controlled parameters. Nanocarriers and magnetic field-assisted methods also show promise for drug delivery, with ongoing research to improve efficacy and safety.