Promising treatment
Families affected by fragile X syndrome can let out a modest cheer this week: the largest-ever randomized trial of a drug to treat the syndrome has just cleared its second phase.
The drug, dubbed STX209, is further along than any other treatment for an autism-related disorder. If it passes the next, more rigorous testing phase, it could be in clinics within a few years.
At a meeting on Saturday of the National Fragile X Foundation, Seaside Therapeutics, a small biotech in Cambridge, Massachusetts, announced that in 15 children who had both fragile X syndrome and severe social impairments, STX209 significantly improved scores on several tests of social behaviors.
The drug didn't work on everyone in the trial, but for some, it was remarkable. According to the lead investigators, some participants improved so much that they stopped taking other medications, such as antidepressants and antipsychotics, which can have nasty side effects. The researchers are indefinitely continuing an 'open-label' extension study, in which the participants knowingly take the drug while the company collects data on safety and long-term effects.
In 2002, Mark Bear, one of Seaside's founders, famously showed that mouse models of fragile X syndrome have excessive activity of the chemical messenger glutamate. Accordingly, STX209 stimulates gamma-amino butyric acid type B receptors, which effectively dampen glutamate signaling. Most of the other drugs in development for fragile X either also stimulate pathways that inhibit glutamate, or directly block glutamate receptors.
Although STX209 showed a trend of improving irritability and social problems in the wider group of 54 children and adults with the syndrome, the results were not statistically significant.
Seaside is also running a preliminary open-label study to test whether STX209 improves irritability in 30 children with autism. About one in three of individuals with fragile X syndrome also have autism.
It's unlikely that drugs developed for fragile X will improve the full range of symptoms on the autism spectrum, but given the current dearth of treatments, even small gains are reason enough for good cheer.
Comments
Hello,
I read the article in Discover Magazine in 2007, discovering a way to reverse Fragie X Syndrome, by the Picower Institute for Learning and Memory at MIT.
The article said it would take 2-5 years of testing the medication. How is the testing coming along?
I have two adult children, 46 & 43 years old, with FXS. Would this medication work on adults, or will it only help young children as they are growing?
I am interested in finding out any progress that has been made.
Thank you for your help.
Sandra K. O'Brien
Hi Sandra,
Although the advancements in drug treatments for fragile X are very exciting (probably more so than anything else we write about on this site), the process of rigorously testing new compounds and getting FDA approval is long and difficult. I can only imagine how frustrating it must be for parents.
The only thing I could find about FX in Discover Magazine in 2007 is an article about an enzyme called PAK kinase: http://discovermagazine.com/2007/sep/the-goldilocks-method-for-curing-autism. When the article was written, the researchers had not yet developed a drug to capitalize on the findings. As far as I can tell from the lead researcher's website (http://web.mit.edu/picower/faculty/tonegawa.html), there still isn't any such drug.
But 2007 was also the year that Mark Bear (also of MIT) reported that mGluR inhibitors reversed fragile X symptoms in mice. This was widely reported in the popular press; our article about this work is here: https://sfari.org/news/-/asset_publisher/6Tog/content/fragile-x-symptoms-reversed-in-mice?redirect=/news.
This is the basic research that Seaside Therapeutics has been following up on. You can see the status of all of the Seaside fragile X trials (several of which are on adults) here: http://www.seasidetherapeutics.com/programs/fragile_x_clinical_trials.php. I would guess that it will still be one or two years, at least, before these drugs are on the market.
This is just one of the approaches to treating fragile X and autism; I recently wrote an article about Big Pharma's interest in these disorders, and all of the various drugs in development, here: https://sfari.org/news/-/asset_publisher/6Tog/content/pharma-companies-set-their-sights-on-autism?redirect=/news.
Thanks for reading!
Hello,
There is a newspaper article written in the Spokesman Review (Spokane, Washington). You can check it out at: http://m.spokesman.com/stories/ 2011/may/17x-factor/
It talks about a new treatment for Fragile X syndrome "minocycline" and the success it is having on a 14 yr. old boy.
Would it be possible for you to e-mail me what your findings on this common drug are and if it is being tested on adults.
My son Michael is now 44 yrs. and my daughter Susan is 47 yrs.
They say that there are several drugs that might correct or reverse Fragile X & autism. Large scale trials are going on now and may take years.
I would appreciate any information you could give me.
Thank you,
Sandra O'Brien
Hi Sandra,
Unfortunately that article link appears to be broken.
Minocycline is an antibiotic. A few studies have suggested that it may be effective for improving some symptoms of fragile X but, from what I can tell, the evidence so far is pretty weak.
Here is a link (open-access) to a recent study of a trial testing minocycline on patients with FXS. (Note, though, that it was an open-label trial, which means that the parents and participants knew they were getting the drug, and were therefore susceptible to the placebo effect.)
http://www.biomedcentral.com/1471-2377/10/91
Thanks for reading SFARI.