This program project envisions running two small proof of concept phase I clinical trials in human subjects. To facilitate the work of this program project grant, Pathologica will be responsible for all aspects of the manufacture, quality control, and quality assurance required to produce an investigational new drug. This component includes, the manufacture of the compound(s), packaging of the drug(s), stability testing, production of clinical investigator brochures, and filing of the INDs for both trials. The first trial is envisioned to involve the polyamine biosynthesis inhibitor PA-001 in the setting of HIV associated dementia and related syndromes. PA-001 has shown excellent activity against SIV encephalitis in rhesus macaque model (see Project 2: Animal model studies for more details). The compound for the second trial will be chosen based on the results of the in vitro and animal studies performed during the first two years of the program project, but will also be a polyamine biosynthesis inhibitor. Pathologica LLC is fortunate to have rights to evaluate and commercialize many PBIs including the polyamine analog CG47, and the PBI manufacture core will ensure that sufficient quantity and quality of these polyamine analogs will be available for comparative studies with PA-001 as described more fully in Projects 1 and 2 of this program project grant. To provide the drugs Pathologica will be assisted by Dr Fredrick Johnson, who has more than 20 years of experience in the manufacture and quality assurance testing of both small molecule and biological pharmaceutical products.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19MH081835-03
Application #
7812200
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
3
Fiscal Year
2009
Total Cost
$201,915
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Chow, Dominic C; Kagihara, Jamie M; Zhang, Guangxiang et al. (2016) Non-classical monocytes predict progression of carotid artery bifurcation intima-media thickness in HIV-infected individuals on stable antiretroviral therapy. HIV Clin Trials 17:114-22
Soulas, Caroline; Autissier, Patrick J; Burdo, Tricia H et al. (2015) Distinct phenotype, longitudinal changes of numbers and cell-associated virus in blood dendritic cells in SIV-infected CD8-lymphocyte depleted macaques. PLoS One 10:e0119764
Meyza, Ksenia; Nikolaev, Tomasz; Kondrakiewicz, Kacper et al. (2015) Neuronal correlates of asocial behavior in a BTBR T (+) Itpr3(tf)/J mouse model of autism. Front Behav Neurosci 9:199
Jin, Xia; McGrath, Michael S; Xu, Hua (2015) Inhibition of HIV Expression and Integration in Macrophages by Methylglyoxal-Bis-Guanylhydrazone. J Virol 89:11176-89
Ndhlovu, Lishomwa C; Umaki, Tracie; Chew, Glen M et al. (2014) Treatment intensification with maraviroc (CCR5 antagonist) leads to declines in CD16-expressing monocytes in cART-suppressed chronic HIV-infected subjects and is associated with improvements in neurocognitive test performance: implications for HIV-associa J Neurovirol 20:571-82
Chow, Dominic; Nakamoto, Beau; So, Edison et al. (2013) Rates of autonomic dysfunction in HIV patients receiving antiretroviral therapy. J Neurovirol 19:511-2
Nakamoto, Beau K; Shikuma, Cecilia M; Ogata-Arakaki, Debra et al. (2013) Feasibility and potential role of ferumoxytol-enhanced neuroimaging in HIV-associated neurocognitive disorder. J Neurovirol 19:601-5
Kallianpur, Kalpana J; Shikuma, Cecilia; Kirk, Gregory R et al. (2013) Peripheral blood HIV DNA is associated with atrophy of cerebellar and subcortical gray matter. Neurology 80:1792-9
Shikuma, Cecilia M; Nakamoto, Beau; Shiramizu, Bruce et al. (2012) Antiretroviral monocyte efficacy score linked to cognitive impairment in HIV. Antivir Ther 17:1233-42
Kallianpur, Kalpana J; Kirk, Gregory R; Sailasuta, Napapon et al. (2012) Regional cortical thinning associated with detectable levels of HIV DNA. Cereb Cortex 22:2065-75

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