Under the parent grant, Tetra Discovery Partners is developing phosphodiesterase 4B (PDE4B) allosteric inhibitors as a treatment for major depressive disorder. Uniquely, the Tetra drug will address inflammation as a contributor to depression. This is a new mechanism of action for an antidepressant drug which should prove complimentary to current therapeutics. The company estimates that 10-20% of patients with depression have co-morbid inflammation and will be ideal candidates for the Tetra drug. Addressing inflammation will target currently untreatable patients, such as those receiving interferon-? (IFN?) for viral illness, depressed patients with co-morbid psoriasis, inflammatory bowel disease, traumatic brain injury, or post-traumatic stress disorder. Given the limitations of current treatments, there is a need for new medications with novel mechanisms of action. The supplemental fund request will allow the company to assess the benefit of lead PDE4B allosteric inhibitors in preclinical mouse models of Alzheimer?s disease.

Public Health Relevance

The prevalence of major depression is staggering with around 20% of people experiencing depression at some point in their lives. Thus, there is a need for new medications with novel mechanisms of action. The company proposes to develop phosphodiesterase-4B (PDE4B) inhibitors with a unique antidepressant/anti-inflammatory profile for treating depression. The supplemental funding request will allow assessment of lead compounds in preclinical mouse models of Alzheimer's disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
3R44MH091791-08S1
Application #
9707027
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Grabb, Margaret C
Project Start
2011-05-23
Project End
2019-08-31
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
8
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Tetra Discovery Partners, Inc.
Department
Type
DUNS #
967529939
City
Grand Rapids
State
MI
Country
United States
Zip Code
49503
Titus, David J; Wilson, Nicole M; Alcazar, Oscar et al. (2018) A negative allosteric modulator of PDE4D enhances learning after traumatic brain injury. Neurobiol Learn Mem 148:38-49
Wilson, Nicole M; Gurney, Mark E; Dietrich, W Dalton et al. (2017) Therapeutic benefits of phosphodiesterase 4B inhibition after traumatic brain injury. PLoS One 12:e0178013
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
Titus, David J; Wilson, Nicole M; Freund, Julie E et al. (2016) Chronic Cognitive Dysfunction after Traumatic Brain Injury Is Improved with a Phosphodiesterase 4B Inhibitor. J Neurosci 36:7095-108
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