If you missed our September 2025 Thought Leadership webinar on Unlocking the Brain – Innovations in CNS Drug Discovery and Neurodegenerative Treatment, you can catch up on demand now and this article provides a brief overview of the insightful discussion. Leading voices from academia and industry came together to discuss the future of CNS drug discovery and the treatment of neurodegenerative conditions. This one-hour webinar captures an exclusive interview with Dr. Emma Mead, Chief Scientific Officer at Alzheimer’s Research UK, and a lively panel discussion with Professor Moein Moghimi of Newcastle University, Dr. Shadi Farhangrazi of SMDG Discovery Group, and Dr. Ralph Minter of Alchemab – examining new technologies, translational approaches, and therapeutic opportunities while addressing the challenges that continue to hinder progress in this complex field.
Dr. Mead opens by highlighting the priorities at the Oxford Drug Discovery Institute, which include identifying and validating new therapeutic targets for conditions such as Alzheimer’s, Parkinson’s, and vascular dementia. Genome-wide association studies have emphasized neuroinflammation, endolysosomal dysfunction, and organelle abnormalities as critical drivers of pathology. These insights are being leveraged to identify tractable targets, validated using human iPSC-derived models, before progressing to screening cascades and small molecule development. Mead emphasises the importance of co-pathologies, noting that vascular dementia often overlaps with Alzheimer’s disease, representing a promising but underexplored avenue for therapeutic intervention.
Technological innovation underpins much of this work. Mead describes how isogenic iPSC models, complex tri-culture assays, and organoid systems are transforming target validation, while artificial intelligence and machine learning approaches enhance protein structure analysis and virtual screening. These tools enable evaluation of modalities such as PROTACs, long considered unsuitable for CNS disorders, and accelerate biomarker discovery, crucial for patient stratification and clinical readiness. Advances in CNS shuttle technologies are also expanding therapeutic possibilities. Receptor-mediated transport, particularly through transferrin receptors, has enabled antibody delivery across the blood–brain barrier, with potential to extend this approach to PROTACs, peptides, and other biologics. Mead also highlights ultrasound-mediated opening of the blood–brain barrier as a promising non-pharmacological strategy.
Nevertheless, significant challenges remain. Mead notes concerns with receptor distribution and affinity in shuttle systems, structural considerations in ligand binding, and the risks of off-target effects or toxicity with lipid nanoparticles. Translational research must therefore balance innovation with careful validation. Preclinical models present another hurdle: while animal systems offer insight into specific pathologies and pharmacodynamics, no model faithfully replicates the complexity of human neurodegenerative disease. Advances in humanised mouse models provide some progress, but Mead stresses the continued importance of human-based systems, coupled with rigorous decision-making processes that incorporate clear milestones and ‘no-go’ points.
The lively panel discussion expands on these themes. Professor Moghimi emphasises that despite decades of research, delivery systems such as exosomes, viral vectors, and nanoparticles remain inconsistent and often poorly understood at the level of blood–brain barrier biology. He advocates for fundamental research into barrier dynamics, alongside combinatorial approaches that address inflammation - a central yet underappreciated driver of neurodegeneration. Farhangrazi echoes these concerns, particularly regarding the limitations and safety issues of antibody-based approaches, while noting her company’s advances in receptor-mediated delivery platforms. She envisions a future in which neurodegenerative diseases are treated with cocktails of therapies, combining anti-inflammatory agents, nucleic acids, and other modalities tailored to disease stage and patient need.
Minter noted that even without shuttle technologies, some amyloid-targeting antibodies have demonstrated pharmacodynamic effects. Recent receptor-mediated shuttle systems appear to boost brain penetration substantially. Moreover, antibody engineering can reduce inflammatory side effects, offering opportunities for refinement. He also outlined Alchemab’s approach of studying resilient patients to identify shared antibodies, using these as a basis for novel target discovery.
Another strong theme throughout the webinar was the importance of collaboration. Dr. Farhangrazi calls for new models of partnership that bring academia, industry, non-profits, and investors together more effectively, overcoming barriers such as lengthy contractual negotiations. Professor Moghimi stresses the importance of training the next generation of scientists to value patience and rigour over the pressure for rapid publication. Dr. Minter emphasises the benefits of industry–academia partnerships, which provide access to cutting-edge models and clinical expertise, though he acknowledged that administrative processes can slow progress.
Our expert panel agrees that much remains to be learned about the fundamental biology of the blood–brain barrier and the mechanisms driving neurodegenerative disease. At the same time, innovations in iPSC models, AI-driven target discovery, and novel delivery technologies are creating new opportunities for therapeutic development. All panellists’ express optimism that combination strategies, involving gene therapies, antibodies, and small molecules will be central to future treatment – and the discussion concludes that the ultimate goal remains unchanged: to accelerate translation from discovery to clinic and deliver effective therapies to patients living with neurodegenerative disease.
