Researchers at UC Berkeley and Pfizer Worldwide Research and Development reported Tuesday their discovery of a new method to prevent the formation of disease-bearing proteins within cells.
The small molecule, named PF-06446846, was found to inhibit a protein called PCSK9 that plays a role in controlling the amount of LDL-C, or “bad cholesterol,” in an organism, according to the research article. PF-06446846 inhibits human ribosomes, cellular structures that translate DNA into new proteins, from producing PCSK9 proteins.
The discovery was co-authored by UC Berkeley researchers Jennifer Doudna and Jamie Cate, among others. It was published Tuesday in the Public Library of Science, or PLOS.
“Particularly surprising was the degree of specificity — the drug only stalled ribosomes that were synthesising a handful of the thousands of proteins that a cell makes,” said PLOS Biology editor Roli Roberts in an emailed statement.
This discovery may lead to pathways for future small molecules to selectively target disease-mediating proteins that scientists previously thought could not be treated with drugs, according to the research article. Cate added that the method could eventually be used to treat neurological diseases and cancer.
Although both antibiotics and the new method treat diseases by eliminating the production of disease-mediating proteins, Cate said the new method from the study works very differently from antibiotics. Antibiotics cause organic molecules to target protein synthesis by blocking translation of bacteria. In the research, however, they were able to specifically inhibit certain human ribosomes without disturbing the cells containing them.
According to Roberts, the immediate medical implications of this research are still limited because tests on rats showed that PF-06446846 can only be given in a certain dosage before the subject experiences side effects related to blood production.
Roberts added that in the long-term this research may lead to the creation preventative drugs that attack the source of unwanted proteins before they are formed.
“From my perspective this was a really great collaboration between a pharmaceutical company Pfizer and academics like me to do fundamental research that in the longer run is going to have practical benefits,” Cate said. “It’s not a project that my group could have developed on its own, and not one that Pfizer could have developed, but the collaboration was really what made it possible.”