A team led by a longtime Oregon Health & Science University researcher has demonstrated in mice what could be a revolutionary new technique to cure a wide range of human diseases — from cystic fibrosis to cataracts to Alzheimer’s disease — that are caused by “misfolded” protein molecules.
Misfolded protein molecules, caused by gene mutation, are capable of maintaining their function but are misrouted within the cell and can’t work normally, thus causing disease. The OHSU team discovered a way to use small molecules that enter cells, fix the misfolded proteins and allow the proteins to move to the correct place and function normally again.
The researchers were led by P. Michael Conn, Ph.D., who was a senior scientist in reproductive sciences and neuroscience at OHSU’s Oregon National Primate Research Center and professor of physiology and pharmacology, cell biology and development and obstetrics and gynecology at OHSU for the past 19 years. This month, Conn joined Texas Tech University Health Sciences Center as senior vice president for research and associate provost.
The team’s work will be published this week in the early online edition of the Proceedings of the National Academy of Sciences. The work was the culmination of 13 years of work on the process by Conn andJo Ann Janovick, former senior research associate at the ONPRC who is now also at TTUHSC. Richard R. Behringer, Ph.D., from the University of Texas MD Anderson Cancer Center, M. David Stewart, Ph.D., from the University of Houston, and Douglas Stocco, Ph.D., andPulak Manna, Ph.D., from the department of biochemistry/microbiology at TTUHSC, also contributed to the work.
Conn and his team perfected the process in mice, curing them of a form of disease that causes males to be unable to father offspring. The identical disease occurs in humans and Conn believes the same concept can work to cure human disease as well.
“The opportunity here is going to be enormous,” said Conn, “because so many human diseases are caused by misfolded proteins. The ability of these drugs – called ‘pharmacoperones’ – to rescue misfolded proteins and return them to normalcy could someday be an underlying cure to a number of diseases. Drugs that act by regulating the trafficking of molecules within cells are a whole new way of thinking about treating disease.”