Fiscal Year:
2007
Title:
Novel Engineered Synthetic Metallodrugs Directed Against HCV
Agency:
HHS
Contract:
1R43AA016712-01
Award Amount:
$256,722.00
Abstract:
DESCRIPTION (provided by applicant): Alcohol is a high risk factor in hepatitis C virus (HCV) infection and increases the severity of the infection. It has been estimated that 35% of alcohol-dependent people carry HCV. HCV is associated with cirrhosis, liv
er failure, and hepatocellular cancer, and alcohol exacerbates all of these pathogenic conditions. The major purpose of this application is to create new metallodrug constructs that catalytically and irreversibly destroy the virus in infected cells.
HCV is a positive, single-stranded RNA enveloped virus that contains about 10,000 nucleotides that are translated into a single polyprotein of about 3,000 amino acids. A full length negative strand is the intermediate that contains the core, envelope and
non-structural protein regions. Substantial sequence variation is caused by hypervariable regions in the envelope region, thus contributing to the difficulty in making robust vaccines and therapeutic drugs. The polyprotein is converted by host and viral p
roteases into structural and non-structural proteins necessary for viral replication and infection. About 10,000 people die each year in the US as a result of HCV infection. Most hepatitis is caused by HCV that is transmitted through contact with infected
blood, sexual contact, or contact between fetus or infant and mother. About 85% of those with acute infections develop chronic infections of HCV. Chronic infection is almost never spontaneously cleared without treatment and alcohol increases the infection.
Millions of people worldwide (about 170,000,000 people or 2% of the world's population) are infected and a significant portion of the US population (about 4 million) carry HCV. Current therapy uses a combination of interferon and ribavirin. Treatment is e
xpensive and not very effective. Moreover, it does not clear the virus from the patient. MetalloPharm has novel technology that uses an innovative metallodrug to catalytically inactivate the virus and clear it from the infected cell. New metallodrugs will
be made and tested for their ability to inhibit the virus in cell culture assays using human cells infected with HCV replicons, which are subgenomic pieces of HCV. After optimization, selected constructs will be tested for their pharmacokinetic and biodist
ribution properties in rodents. Alcohol and hepatitis C virus (HCV) are a deadly combination. HCV infects about one third of alcoholics. Metallopharm has created novel technology (metallodrugs) that have the potential to clear the virus from infected cells
and thereby improve the ineffective and expensive treatment that is currently offered to patients.
Business Contact:
Donna Palmer
Small Business Information at Submission:
METALLOPHARM, LLC
METALLOPHARM, LLC 3225 MONTCLAIR AVE LEWIS CENTER, OH 43035
EIN/Tax ID:
114053584
DUNS:
N/A
Number of Employees:
N/A
Woman-Owned:
No
Minority-Owned:
No
HUBZone-Owned:
No