Abstract

Alzheimer's disease (AD) is an increasing medical burden due to the aging demographics of the US population. The most common form of dementia among older adults, AD affects parts of the brain important for memory formation and retrieval, seriously impairing a person's ability to live independently and cope with daily activities. In collaboration with the NIH Blueprint Neurotherapeutics Program, we seek to develop phosphodiesterase Type 4 (PDE4) allosteric modulators for improving cognition in accordance with the Target Product Profile below. Ideally, the therapeutic will improve cognition in MCI patients and impact AD pathophysiology, thereby slowing conversion to probable AD. Drug PropertiesMinimum Acceptable ResultIdeal ResultPrimary Drug IndicationImprovement of cognition in persons with Mild Cognitive Impairment (MCI) due to probable ADSlowing of conversion from MCI to probable ADPatient PopulationPatients with MCI due to probable AD according to the NIAA/AA working group criteriaPatients with MCI due to probable AD according to the NIAA/AA working group criteriaDelivery ModeOralOralTreatment DurationChronicChronicRegimenOral, once dailyOral, once daily

Public Health Relevance

With a growing elderly population in industrialized nations world-wide, drugs to treat Alzheimer's disease (AD) are a critical unmet medical need. We are seeking to develop a new treatment for AD based on allosteric modulation of phosphodiesterase 4D (PDE4D). Ideally, the treatment will reverse or stabilize cognitive decline due to AD.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01NS078034-03
Application #
8675970
Study Section
Special Emphasis Panel (ZNS1-SRB-E (52))
Program Officer
Cywin, Charles L
Project Start
2012-06-15
Project End
2017-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
3
Fiscal Year
2014
Total Cost
$235,406
Indirect Cost
$35,355

  Institution

Name
Tetra Discovery Partners, LLC
Department
Type
DUNS #
967529939
City
Grand Rapids
State
MI
Country
United States
Zip Code
49506

  Publications

Zhang, Chong; Xu, Ying; Zhang, Han-Ting et al. (2017) Comparison of the Pharmacological Profiles of Selective PDE4B and PDE4D Inhibitors in the Central Nervous System. Sci Rep 7:40115
Gurney, Mark E; Cogram, Patricia; Deacon, Robert M et al. (2017) Multiple Behavior Phenotypes of the Fragile-X Syndrome Mouse Model Respond to Chronic Inhibition of Phosphodiesterase-4D (PDE4D). Sci Rep 7:14653
Gurney, Mark E; D'Amato, Emily C; Burgin, Alex B (2015) Phosphodiesterase-4 (PDE4) molecular pharmacology and Alzheimer's disease. Neurotherapeutics 12:49-56
Hagen, Timothy J; Mo, Xuesheng; Burgin, Alex B et al. (2014) Discovery of triazines as selective PDE4B versus PDE4D inhibitors. Bioorg Med Chem Lett 24:4031-4
Fox 3rd, David; Burgin, Alex B; Gurney, Mark E (2014) Structural basis for the design of selective phosphodiesterase 4B inhibitors. Cell Signal 26:657-63