One of the major problems with developing treatments for medicine is the inability for certain compounds to pass through the blood/brain barrier. Larger, more effective compounds are known to exist, but infeasible to utilize due to their inability to get to the infected cells.
However, a study from The Scripps Research Institute (TSRI) offers an intriguing new way to work around this problem. Primarily, by convincing the diseased cell to commit acts of sabotage on itself.
"We're using a cell as a reaction vessel and a disease-causing defect as a catalyst to synthesize a treatment in a diseased cell," said TSRI Professor Matthew Disney. The smaller compounds which were previously ineffective against disease have been found to take on new life when they become bound to targeted cells expressing an RNA defect.
The study focused on cells affected with myotonic dystrophy type 2, a mild form of muscular degeneration that effects roughly 1 in 8000 people worldwide (this number refers to type 1 and 2 together, exact proportions are unknown). The cause of this disease is a defect within RNA cells, where a series of four nucleotides are repeated more times than normal in an individual’s genetic coding. In this case, a cytosine-cytosine-uracil-guanine (CCUG) repeatedly binds to the protein MBNL1, rendering it inactive and causes the RNA division abnormalities that, in turn, lead to the disease.
During this study, a pair of small molecules, developed by the scientists, bind to adjacent poles of the defective RNA. Think of it like two hydrogen atoms in an H2O molecule. But unlike a water molecule that would have natural attraction between smaller and larger molecules, the two smaller molecules reach out to each other, to do what Disney describes as “holding hands”.
The effect this has is to create a new, larger, compound within the infected area, utilizing the infected cells as to create their own destruction. The two small molecules bind so tightly to the defective cell, that they reverse disease defects on the molecular level. Effectively, destroying the disease from within. Cue Independence Day soundtrack.
Such an application opens the door to developing countless amounts of treatments that would otherwise not be able to pass through the blood/brain barrier. Bypassing the need for injections of drugs, and instead creating the drug within the human body itself. The original notion behind this application was first developed by Nobel laureate K Barry Sharpless, a chemist at TSRI, who dubbed it “click chemistry”.
“In my opinion, this is one unique and a nearly ideal application of the process Sharpless and his colleagues first developed,” Disney said.
Further research continues with the hope of uncovering new treatments for similar RNA defective diseases such as ALS, Huntington’s disease and more than 20 others where there is no known cure.