Researchers Find Potential Target to Treat Several Diseases

Attacking protein could potentially treat a number of conditions, including the Ebola virus, brain cancer, and hepatitis.

Researchers have found a potential therapeutic target for the treatment of several diseases, including brain cancer, the Ebola virus, influenza, hepatitis, and bacteria such as MRSE and MRSA.

In a pre-clinical study published in the December 2014 issue of the Journal of Cellular Physiology, researchers evaluated the use of a drug combination of the clinically tested OSU-03012 (AR-12) and FDA approved Phosphodiesterase 5 Inhibitors (Viagra, Cialis) to target the GRP78 protein, and other related proteins. The researchers were able to prevent the replication of several major viruses in infected cells while making antibiotic-resistant bacteria vulnerable to treatment with common antibiotics.

The study also revealed evidence that brain cancer stem cells were killed and provided data in a number of brain cancer stem cell types.

"Basically, we've got a concept that by attacking GRP78 and related proteins: (a) we hurt cancer cells; (b) we inhibit the ability of viruses to infect and to reproduce; and (c) we are able to kill superbug antibiotic-resistant bacteria," study lead investigator Paul Dent, PhD, said in a press release.

GRP78 is part of a family of proteins called chaperones, which help to shape chains of amino acids into proteins and keep them active in the correct shape. The OSU and Viagra drug combination attacks chaperone proteins, which kills the cancer cells as a result.

The OSU and Viagra combination has also been found to eliminate tumor cells without harming normal tissues like the liver and the heart in mice. The combination reduced levels of proteins in the mouse brain that are responsible for producing tumor cells resistant to chemotherapy, which stops the treatment from entering the brain and killing cancer cells.

With the drug combination's effect on GRP78 in cancer cells, the researchers then set out to target the protein in other infectious diseases, including viruses and bacteria.

Cancer cells and cells infected with a virus produce extra proteins compared with normal or uninfected cells, which makes the chaperone proteins vital. The OSU and Viagra drug combination was found to decrease the infectivity by reducing viral receptor expression on the surface of target cells and by preventing viral replication in infected cells.

The drug combination was found to reduce expression of viral receptors for the Ebola virus, Marburg virus, hepatitis A, B, and C, and Lassa fever viruses. Additionally, the drug combination decreased expression of oncogene receptors in cancer cells and reduced expression of the equivalent protein in bacteria called Dna K.

This subsequently caused cell death in pan-antibiotic resistant forms of E. coli, MRSE, MRSA, and N. gonorrhoeae.

"The findings open an avenue of being able to treat viral infections, infections that certainly most people would say we'll never be able to treat. They prove that GRP78 is a ‘drugable’ target to stop viruses from reproducing and spreading," Dent said. "In the case of bacteria, we have a new antibiotic target, Dna K, that if we're careful and only use the OSU drug in hospitals, we've got something that can help to treat the superbugs."