The Blood-Brain Barrier: A Defensive Line Still Missing its Star Player, Neuroprotection

By Aniv Brukner • December 11, 2025

Executive Summary Drug delivery vs. neuroprotection: The pharmaceutical industry has heavily invested in blood brain barrier (BBB)-crossing technologies (e.g., Roche’s Brainshuttle™, GSK’s Grabody-B, and intranasal agents such as SPRAVATO), but far less in therapies that maintain or restore barrier integrity. Neuroprotective approaches: Strategies currently under evaluation include modulation of endothelial cell transporters, upregulation of tight junction proteins (e.g., claudins and occludins), suppression of neuroinflammatory pathways, exogenously supplying extracellular matrix-derived biopolymers to rescue gaps in the endothelium triggered by the loss of tight junctions, and transplantation of neurovascular-supporting cells such as pericytes. Challenges: Failures such as natalizumab’s (TYSABRI) inability to reduce seizure frequency in drug-resistant focal epilepsy underscore the heterogeneity of BBB-related pathology and the need for tailored therapeutic approaches; natalizumab targets the BBB’s α4-integrin-VCAM-1 interaction, a pathway central to multiple sclerosis etiology, but likely less relevant in epilepsy. Outlook: Approximately ten companies are currently exploring neuroprotective candidates across various indications. However, most programs have remained in early- to mid-stage development for an extended period. Accelerating progress by strategically shifting gears in the discovery and development process is therefore of paramount importance: BBB-targeted neuroprotection could be a paradigm-shifting, billion-dollar opportunity, reframing the BBB from an obstacle to a frontline therapeutic target in some disease areas. Success will depend on mapping actionable targets, advancing biomarkers/imaging, and aligning interventions with disease-specific mechanisms.

After recent federal funding cuts, what's next for mRNA therapeutics?

By Stephanos Nicolaou • October 9, 2025

In August 2025, the U.S. Department of Health and Human Services (HHS) announced the termination and restructuring of 22 federally funded mRNA vaccine and therapeutic projects, totaling nearly $500 million under the Biomedical Advanced Research and Development Authority (BARDA). This marks a significant strategic shift away from mRNA platforms toward alternative vaccine technologies, which HHS indicated may offer broader or more durable protection against certain viral threats. The affected projects involved major universities, biotech companies, and pharmaceutical firms. Contracts with Emory University and Tiba Biotech were terminated outright, while funding was reduced or projects de-scoped at Luminary Labs, ModeX, and CSL Seqirus. Pre-award proposals from Pfizer, Sanofi Pasteur, Gritstone, and CSL Seqirus were cancelled, and collaborations involving Moderna-UTMB, AstraZeneca, Access to Advanced Health Institute, and HDT Bio were restructured. Some mature programs by Arcturus Therapeutics and Amplitude were allowed to proceed. These initiatives addressed critical public health priorities, including vaccines for respiratory viruses such as COVID-19, influenza, and RSV, rapid-response pandemic preparedness, novel delivery methods such as inhaled or dry-powder formulations, and universal vaccines targeting viral mutation.