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The long-term goal of our research is to develop safe and effective therapeutics for CNS disorders such as Alzheimer’s disease (AD) and related dementias and acute brain injuries (ICH, TBI) by targeting dysregulated neuroinflammation in the brain. The focus is on identification of signal transduction pathways that mediate the neuroinflammatory responses of activated astrocytes and microglia, and determination of how aberrant glial-neuronal interactions influence neurodegenerative processes. When injury or change occurs in the brain, glia mount a beneficial activation response to fight off the insult and restore the brain to its proper functioning. While a controlled activation response is important in protecting the brain, this beneficial process sometimes gets out of balance and the activation becomes too strong or too prolonged. In CNS diseases, glia are over-activated, producing detrimental proinflammatory cytokines that can contribute to neuron damage and accelerate disease progression. We have developed selective, small molecule experimental therapeutics that suppress proinflammatory cytokine overproduction, and we are developing them into effective future drugs. Most recently, our collaborative studies have resulted in the discovery of new classes of orally active, CNS-penetrant, small molecule drug candidates that modulate glia dysfunction with resultant attenuation of neuropathology progression in animal models. These novel small molecules are candidates for drug development as well as tools to explore the potential of improved neurologic outcomes by restoration of activated glia back towards homeostasis. For example, in collaborative efforts at the biology-chemistry interface, we have shepherded a set of small molecule compounds from design and synthesis, through IND-enabling preclinical development. This led to successful phase I clinical trials with three of our compounds, which are currently being moved into further clinical development.
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论文共 223 篇作者统计合作学者相似作者
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STATISTICA NEERLANDICAno. 3 (2023): 304-321
medRxiv (Cold Spring Harbor Laboratory) (2023)
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Adam D. Bachstetter,Jenny Lutshumba, Edric Winford,Erin L. Abner, Barbra J. Martin,Jordan P. Harp,Linda J. Van Eldik,Frederick A. Schmitt,Donna M. Wilcock,Ann M. Stowe,Gregory A. Jicha,Barbara S. Nikolajczyk
BRAIN COMMUNICATIONSno. 5 (2023)
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Adam D Bachstetter,Jenny Lutshumba, Edric Winford,Erin L Abner, Barbra J Martin,Jordan P Harp,Linda J Van Eldik,Frederick A Schmitt,Donna M Wilcock,Ann M Stowe,Gregory A Jicha,Barbara S Nikolajczyk
Brain communicationsno. 5 (2023): fcad259-fcad259
Acta neuropathologica communicationsno. 1 (2023): 89-19
PloS oneno. 5 (2023): e0286495-e0286495
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Radhika Avadhani,Wendy C Ziai,Richard E Thompson,W Andrew Mould,Karen Lane, Angeline Nanni,Michael Iacobelli,Matthew F Sharrock,Lauren H Sansing,Linda J Van Eldik,Daniel F Hanley, BEACH trial consortium
Neurocritical careno. 2 (2023): 807-815
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