The USC School of Pharmacy department of pharmaceutical sciences and the Keck School of Medicine of USC have been awarded a five-year National Institutes of Health grant to find ways of transporting complex drug molecules into the cells through the lacrimal gland.

The research is led by Sarah Hamm-Alvarez, Gavin S. Herbert Professor and interim chair of the department of pharmaceutical sciences.

Co-investigators include Wei-Chiang Shen, also a professor of pharmaceutical sciences, and Judy Garner, associate professor and assistant dean for faculty affairs at the Keck School. The National Eye Institute made the award.

“We are searching to find out if viral proteins or pieces of proteins are able to carry protein/DNA-based drugs into the cell. While our research is looking specifically at the lacrimal gland, the basic processes we are studying are applicable beyond the eye,” Hamm-Alvarez said.

Finding routes into the lacrimal gland, commonly called the tear gland, allows efficient delivery of peptide, protein or DNA-based therapeutics to treat diseases like Sjogren’s Syndrome.

Since the lacrimal gland sustains the health of the cornea through the release of tear proteins and fluid, delivering these therapeutic agents into the lacrimal gland also treats other corneal diseases and injuries, including scarring resulting from corneal transplant. Sjogren’s Syndrome alone affects over four million Americans.

“Loss of sight ranks among the chief concerns of adults. Whether from disease or injury, if we’re able to treat an ailing lacrimal gland effectively, we then have a much greater chance to preserve sight,” Hamm-Alvarez said.

The grant supports the exploration of drug trafficking at the cellular level. Trafficking is the ability to move membrane-encapsulated materials in and out of a cell. While it is easier to successfully get a small-molecule drug into a specific cell, today’s newer drugs are typically large-molecule drugs and require special trafficking to move them into cells and then to their intracellular targets.

Initially, the research explores the unique interactions that enable a particular protein to efficiently enter the cells of the lacrimal gland, and the identification of the receptor(s) and trafficking mechanisms involved in this process.

“We’re using viral proteins as targeting and delivery agents because a virus has an ability to trick cells into thinking it is what the cell wants,” Garner said. “So by fusing the therapy to the viral pieces, we create a new molecule that is able to gain entrance into the target cell, overcoming barriers and able to render the intended therapy.”

While this project is specifically looking at trafficking into the lacrimal gland, the research bears greatly on the emergent biotech drugs in today’s therapeutic arsenal.

With the exception of insulin, drugs were not typically protein-based as recently as 10 years ago. Now the protein-based therapeutics present the greatest potential for treating cancer, neurodegenerative diseases and autoimmune diseases.

“It is projected that by 2010, we will have double the number of protein-based drugs,” said Shen, whose work also extends to oral and inhalant drug-delivery methods supported by two other NIH grants. “Because these are large-molecule therapies, delivery is a major challenge. Genomics and proteomics have enhanced our ability to identify the right targets. However, unless we can deliver these hopeful drugs to the right targets, they will have no therapeutic use.”

Hamm-Alvarez said, “The impact of drug targeting and delivery is far reaching. If you’re able to target therapeutic molecules [drugs] to the right cells, you are also able to use less drug more efficiently. This saves money on the cost of the drug. Further, the drug only goes to where it is needed, not to the wrong place where it might cause negative side effects. Fewer side effects create more compliant patients.”