Many diseases are caused by proteins that did not fold correctly after translation or have undergone genetic mutation that prevents them from being folded correctly. Repairing correct function has the capability to reverse the disease in mice, and could potentially work on humans as well. After 13 years of study, these results were reported by P. Michael Conn of Oregon Health & Science University and were posted in the Proceedings of the National Academy of Sciences.

There are a number of ways that a misfolded protein could cause disease, such as resulting in receptors, channels, and enzymes that do not function normally. Because cellular functions are not optimal, disease occurs and the entire organism is affected. Cellular structures are very precise, so any deviation from the expected 3D conformation can be devastating. Many diseases are caused this way, including cataracts, cancers, Alzheimer’s disease, type II diabetes, and more. Often, treatments are unable to get to the root of the problem; the improperly folded protein.

This study focused on male mice who were unable to sire offspring, due to an induced mutation in the gonadotropin-releasing hormone receptor (GnRHR), which starts the signal for puberty and fertility. The mutation prevents the GnRHR from activating, and the onset sperm production or ovulation never begin. The same problem affects tens of millions of people worldwide, rendering them infertile. The research team used special drugs, called pharmacoperones, to reverse the genetically-encoded problem by correcting the protein, which allowed the mice to become fertile and make babies. 

Though this technique has worked on individual cells in the past, this is the first documented case of success within a living organism. The researchers are very pleased with these results and are confident that these principles can also be applied to humans for clinical purposes. Though an incredible amount of additional research is required and clinical use is over a decade away, there is a possibility that next-generation treatments for diseases like certain cancer and Alzheimer’s can be treated at the protein level to cure the patient.