One of my personality traits [or defense mechanisms] is that when confronted with a situation that I can not control or that affects me or someone I love in a negative way I tend to study up and research the issue. IÃ¢â‚¬â„¢m sure everyone here did the same thing when they learned that one of their loved ones/children was diagnosed with Fragile X.
So let me point out first I am in no way suggesting anything of the things I am about to tell you about but figured that knowledge sharing is the best thing we can all do. Please know that I am new to the board, new to being a father with a son with Fragile X and that I just need to post this right now.
[I am pretty sure all of you already know all of this so if you do I apologize in advance…]
So here we go friendsÃ¢â‚¬Â¦
What we know Ã¢â‚¬â€œ we know that Fragile X syndrome is a genetic disorder where on the X chromosome the FRM1 produces little to no FRMP. There is also a repeat in the CGG above what is normal [5 Ã¢â‚¬â€œ 55 depending on what resources you are reading]. In permutation there are repeats from 56 Ã¢â‚¬â€œ 200 and in full mutation there are over 200 repeats [my son has 600]. The effects of FX are almost as broad as the autism spectrum of disorders [in my opinion]. Right now they believe that the protein not being produced or under produced by the FRM1 helps in regulating communications between brain cell receptors. They believe that many of the symptoms can be attributed by overactive signaling by group 1 metabotropic glutamate receptors [or GP1 mGluRs]. fruit flies were bred to imitate human fragile X full mutation and drugs that inhibit GP1 mGluRs and given drugs that targeted this mammalian mGluRs and the defective behavior cleared up.
With the mGlurs theory findings and what we know about GP1 mGluRs activation in the brain suggested that many of the symptoms of Fragile X could be simply accounted for by an overactive mGluR signal. mGluR is necessary for normal cerebellar function and by using these drugs [one of which is Lithium chloride] you can calm down the over stimulus and bring brain functions closer to normal.
Also that the full mutation of the FRM1 and lack or underproduction of FRMP which plays an important role in AMPA receptor protein which calms the excitability of brain cell at synapses and maintaining the proper level of excitability or Ã¢â‚¬Å“strengthÃ¢â‚¬Â of these connections.
There was a study funded by FRAXA Research Foundation and carried out by Cortex Pharmaceuticals, Inc on a drug called CX516 Ampalex that has been proven to enhance glutamate transmission in the brain through activation of AMPA receptors.
Though the study didnÃ¢â‚¬â„¢t have the results we would want to see it did suggest that there were Ã¢â‚¬Å“Problems with potency of CX516 in other studies have suggested dosing may have been inadequate for therapeutic effect. In fact, when only subjects treated with an antipsychotic upon entering the CX516 study were analyzed, there appeared to be improvement in global cognitive and behavioral functioning in the CX516-treated group relative to the placebo group. Given the known ability of antipsychotics to potentiate the effect of CX516 in animal models, this would suggest that the CX516 was likely insufficiently potentÃ¢â‚¬Â
Which leaves the door open to more clinical studies.
There was a new recent article [Sept this year] that brings renewed hope to a medication that can help people with fragile X. It goes back to the mGluR5 on the surface of the neurons. When mice were treated with a mGluR5 antagonist called MPEP that they were able to reverse the effects of the mutation. This MPEP is not a suitable drug to use in humans but it puts out a path for researches to follow down in the development of a new drug that could help. They will be starting new clinical studies in the fall on people with Fragile X and these new drugs.
“This is a very hopeful message,” Hagerman said. “This means that there will be very specific treatments that will have an impact in the very near future.”
Now here is the other thing that I found which I would have never thought to be possible until I started my research. All of the problems from Fragile X come from one little gene being in the off state. There is a company that has discovered how to turn on and off genes using something called Zinc Fingers which occur naturally in a nucleus.
LINK - http://www.wired.com/medtech/health/news/2002/02/50100
LINK TO COMPANY - http://www.sangamo.com/index.php
I hope that maybe one day one of these paths will bear fruit for our community. Right now it is all about therapy, OT, PT, speech and calming techniques.
Thanks for letting me babble.