New treatment trials for FXS

Fragile X Syndrome (FXS) is one of the leading causes of mental retardation and developmental disabilities and it tends to have a variable range of expression. This range is due to variations in the mutation of the FMR1 gene. The mutation that is responsible for this disorder is the number of CGC trinucleotide repeats in the 5' untranslated region of the FMR1 gene, and the number of these mutations is what can be used to determine whether an individual has a premutation or full mutation. Typically in normal unaffected individuals, the repeats could number anywhere from 5 to 50, in unaffected male carriers the repeats usually number from 50 to 200, and affected individuals (male and female) will have much longer stretches of these repeats. 

When it comes to risk, increased penetrance is seen when there are affected individuals in each successive generation of a family, a phenomenon that is commonly known as genetic anticipation. Another interesting thing about this disorder is that males tend to be more often and more severely affected than females because females will have two X chromosomes (one that is usually normal and one that is mutated) and X chromosome inactivation is often seen in females. If the mutated X chromosome tends to be turned off more than the normal, unaffected X chromosome, the female would not show any signs of the disease but she would be a carrier for it and could pass it to her children. Mosaicism is also seen from cell to cell in the body, which will often result in a mix of premutation and full mutations being expressed, and depending on the ratio, the disorder could end up being more severe. There are a lot of different factors that play in the severity of the disorder and not all of the factors are known in full, so currently it isn't possible to say with certainty how the disorder will manifest based on genetics alone. 

One of the most recent trials for treatment of this disorder is being run by Zynerba, a Pennsylvania based pharma company, and it uses a transdermal ointment of CBD. In the study all of the patients receive the treatment, there is no placebo. Over a 12-week period, the CBD ointment was applied on the shoulder of FXS patients and then the patients were asked to complete a questionnaire. Eye tracking and biomarkers were also analyzed to help determine the patients' anxiety levels and whether or not their symptoms improved following treatment. There are no conclusive results for the study as of yet because the trials are still ongoing, but all of the studies are focusing on young individuals whose brains have not fully developed yet. 

I think looking into CBD ointments is an interesting approach to treatment, but most patients don't only have anxiety. Although CBD may help with anxiety and other mild symptoms, I doubt that the CBD would work as a blanket treatment. In my option, there needs to be more studies across multiple different age ranges for the CBD ointment. CRISPR-Cas9 may also be something that could be used in studies to see if the mutated X chromosome could be altered in some way. This would be very difficult though because there would need to be a model organism besides humans that could express FXS in the same manner. Regardless, multiple treatments should undergo more trials to hopefully help people with severe FXS symptoms lead a normal life. 

Links: 

The Nature and Consequences of Fragile X Syndrome: 

https://stockton.primo.exlibrisgroup.com/permalink/01SUN_INST/t0oigp/wj10.1002%2Fmrdd.1410010403

Recent Trials for Fragile X Syndrome Offer Hope: 

https://www.the-scientist.com/magazine-issue/recent-trials-for-fragile-x-syndrome-offer-hope-66305