The central dogma of biology is simply that DNA makes RNA makes protein. Messenger RNA (mRNA) transfers the information from DNA and is used to create protein. The question this study ultimately seeks to answer is “How much mRNA is needed to have healthy retinal function in CHM patients?” It is important to know this information when conducting gene therapy clinical trials so an effective “dose” can be delivered.
This study looked at two patients with CHM who had slower vision loss than the other 28 included in another study. These two patients have a unique CHM mutation, a splice site mutation. This mutation disrupts the splicing at intron 7 which should cause exon 7 to be completely skipped and no full-length mRNA to be produced.
This study shows that some full-length mRNA actually is produced by these patients. The levels are low (less than 1% of what an unaffected person would have), but the study hypothesizes that they are high enough to be the reason these patients have better vision and slower degeneration than other patients. While no REP1 protein was discovered in the patient’s blood, the levels may be too low to be detected.
Previous studies, like this one, have claimed that it does not matter the type of CHM mutation you have; if you have a mutation you will lose your vision at a similar rate compared to other mutations. This is still broadly true (as far as we know almost all mutations fall into this category.) But this recent study has highlighted a specific mutation that is unique in that it can be associated with a milder phenotype.
These patients still do have CHM and still are loosing their vision. However, the fact that the slow progression may be due to low levels of CHM mRNA is promising for gene therapy trials. If even a low “dose” of mRNA ends up in a patient’s eye after gene therapy, this may be enough to slow progression.