Thanks for posting Kelsee. The full text of the abstract for the ACC presentation is embargoed until March 6th. I did find an abstract for the AD/PD conference:

SCIENTIFIC PROGRAMME

A06.h  Theme A: β-Amyloid Diseases

A06.h. Cell, Molecular and Systems Biology: Epigenetics, histone modification, DNA methylation

29-Mar-2017 08:00 18:00 

Abstract: 091

APABETALONE, A BET BROMODOMAIN INHIBITOR, SUPPRESSES INFLAMMATORY MEDIATORS IN MICROGLIA THAT CONTRIBUTE TO NEURODEGENERATIVE DISEASE

Co-authors

E. Kulikowski 1, D. Gilham 1, L. Tsujikawa 1, S. Wasiak 1, C. Halliday 1, R. Lind 1, C. Calosing 1, B. Rakai 1, J. Johansson 2, M. Sweeney 2, N. Wong 1

1Resverlogix Corp., Research and Development, Calgary, Canada

 2Resverlogix Corp., Clinical Development, San Francisco, USA

Introduction: Chronic inflammation is prevalent in neurodegenerative disorders. Activated microglia produce proinflammatory cytokines as well as complement components C3 and C1q, which promote aberrant synapse loss and dysfunction. Apabetalone is a small molecule in Phase 3 trials for cardiovascular disease. As an inhibitor of bromodomain and extraterminal domain (BET) proteins, apabetalone regulates gene expression through epigenetics. Clinical trials in cardiovascular patients and preclinical models demonstrate anti-inflammatory effects on factors in the periphery that can infiltrate the brain, suggesting therapeutic potential in neurodegenerative disease. Here we characterize apabetalone’s effects on microglia to mitigate inflammation and processes contributing to neurodegenerative pathology.

Determine whether apabetalone affects proinflammatory activation of microglia and subsequent expression of factors that promote neurodegeneration.

Method: BV-2 microglial cells were stimulated with LPS and interferon-gamma.  Apabetalone’s effect on expression of proinflammatory cytokines and synaptic pruning were examined by real-time PCR. Cellular proliferation and morphology were monitored. 

Results: After proinflammatory stimulation, microglia acquired the condensed morphology associated with a proinflammatory phenotype. Treatment with apabetalone reversed microglia back to a ramified, resting phenotype. Stimulation of microglia induced expression of interleukin-6, interleukin-1beta, monocyte chemoattractant protein 1, complement C3 and C1q. Apabetalone dose dependently opposed induction of these key contributors to neurodegenerative processes. Apabetalone was not cytotoxic and did not impact proliferation.

Conclusion: Apabetalone reduced activation of microglia and suppressed expression of proinflammatory factors that drive chronic neuroinflammation and overactive synaptic pruning associated with cognitive decline. BET inhibition offers a new frontier for neurodegenerative therapeutics through simultaneous regulation of multiple pathogenic processes.