Life Molecular Imaging (LMI) has received a $2.16 million investment from the Alzheimer's Drug Discovery Foundation (ADDF) to advance research into neuroinflammation in Alzheimer's disease. The three-year funding will support the development of [18F]F-DED, an investigational PET imaging agent designed to target monoamine oxidase B (MAO-B), an enzyme closely linked to neuroinflammatory processes.
The research initiative brings together experts from the University Hospital of Ludwig-Maximilian University (LMU) in Munich, Germany, and the Barcelona Beta Brain Research Center (BBRC) in Spain. This collaborative effort combines expertise in neurology, nuclear medicine, psychiatry, and dementia research to explore neuroinflammation's role in Alzheimer's disease progression.
Overcoming Challenges in Neuroinflammation Imaging
Previous attempts to visualize neuroinflammation using PET imaging have been hampered by genetic polymorphisms that affect ligand binding, resulting in inconsistent findings. The [18F]F-DED tracer represents a potential breakthrough in this area, as it specifically targets MAO-B activity, which increases in reactive astrocytes during astrogliosis—a key neuroinflammatory process.
Andrew Stephens, Chief Medical Officer at LMI, highlighted the significance of the ADDF funding: "This new research provides a unique opportunity to investigate the spatial and temporal dynamics of neuroinflammation and its association with established biomarkers."
The research team anticipates that [18F]F-DED PET imaging will provide critical insights into both sporadic and genetically predisposed Alzheimer's patients, potentially bridging knowledge gaps about neuroinflammation's contribution across different disease stages.
Exploring Neuroinflammation's Role in Disease Progression
Matthias Brendel, Professor for Nuclear Medicine at LMU, emphasized the potential mechanistic insights: "Neuroinflammation could be a potential key driver in the spread of tau pathology to the cortex in Alzheimer's disease. Leveraging PET imaging to explore its role presents a unique opportunity to deepen our understanding of disease progression."
The project aims to combine data from diverse Alzheimer's disease cohorts to unravel the complexities of how the disease advances. Gemma Salvadó Blasco, Group Leader of Neuroimaging Research at BBRC, expressed enthusiasm about the collaboration: "By combining data from diverse Alzheimer's disease cohorts, we aim to unravel the complexities of disease progression. We're thrilled to embark on this exciting journey."
Howard Fillit, MD, Co-Founder and Chief Science Officer of the ADDF, emphasized the potential clinical impact: "PET-Imaging tools provide important insights into understanding Alzheimer's disease and other neurodegenerative disorders and are integrated now into clinical care. New imaging tools exploring neuroinflammation may offer a non-invasive approach to visualize astrocyte activity alongside established biomarkers to further examine the relationship between inflammation and Alzheimer's."
Technical Aspects of [18F]F-DED
The PET tracer [18F]F-DED is a deuterated deprenyl derivative specifically designed to bind preferentially to areas with increased MAO-B activity. Neuroinflammation represents a key pathologic mechanism in many neurodegenerative diseases, including Alzheimer's, movement disorders, and multiple sclerosis.
In the brain, neuroinflammation can be mediated by reactive astrocytes (astrogliosis), which show increased activity of the MAO-B enzyme. By targeting this specific molecular pathway, researchers hope to gain more consistent and reliable imaging results than previous approaches.
Broader Implications for Alzheimer's Research
If successful, this innovative approach could significantly enhance our understanding of Alzheimer's disease pathophysiology. By visualizing neuroinflammatory processes alongside established biomarkers, researchers may uncover new insights into how inflammation contributes to disease progression and potentially identify new therapeutic targets.
The ADDF's investment in this project aligns with its mission to accelerate drug discovery for Alzheimer's disease. The foundation has played a pivotal role in bringing the first Alzheimer's PET scan (Amyvid®) and blood test (PrecivityAD®) to market and continues to support innovative research approaches.
This collaboration between LMI, academic institutions, and the ADDF represents a significant step forward in Alzheimer's research, potentially opening new avenues for both diagnosis and treatment of this devastating neurodegenerative disease.
