Do ‘protective mutations’ hold a cure for PKU?

That’s the question I asked after watching a TED Talk from Stephen Friend, co-founder of Sage Bionetworks. During the presentation, Friend describes an ambitious initiative called the Resilience Project: A Search for Unexpected Heroes, which flips traditional scientific research on its head by suggesting that rather than studying those people who are already sick, we should be studying those people science tells us would be sick with a rare disease, but for some reason have remained healthy.

The premise of the talk, titled The hunt for “unexpected genetic heroes,” asks whether having a closer look at the protective mutations of these “resilient” individuals would provide a pathway for developing new treatments or preventing diseases all together. Here’s the full video presentation:

Naturally, upon finishing the video, I immediately thought the Resilience Project might have some relevance to PKU research. That’s because there are a few, rare cases in the PKU community of individuals who are high-functioning, off-diet phenylketonuria patients, meaning that despite having what is medically considered to be dangerously high phenylalanine levels, these folks are still able to function with a high-level of intellect and lead normal, productive lives.

Friend’s TED Talk ends with a call to action—for individuals to become engaged by voluntarily submitting their DNA to the project—but there was little detail on how to go about doing so. After finding the Resilience Project’s website, and scrolling through much of its content, I was pleasantly surprised to learn that phenylketonuria (PAH) is one of the 195 metabolic gene disorders the group is looking to study. Pretty cool, huh?

After becoming disconnected from the PKU community for the 18 years that I was off-diet, I never did understand why I seemed to function just fine. But as I started to delve back into the world of PKU in 2008, I quickly started to hear in various circles about a mutation theory called the blood-brain barrier. Virginia Schuett’s PKU News has a good description for explaining the blood-brain barrier’s role in why some PKU patients are less affected by high-phe levels than others.

“There is the occasional individual with PKU, who despite poor control of the diet and chronic marked elevations of blood phe seems to escape any significant neurological impairment. It is suspected that such individuals may be protected at the level of the “blood-brain barrier.” The blood-brain barrier serves to protect the brain from exposure to potentially toxic chemicals in the bloodstream.”

Although I cannot confirm that the blood-brain barrier mutation is what the folks at the Resilience Project are specifically studying with regard to PKU, I would not be surprised if it was at least on their radar.

The Resilience Project defines an “unexpected hero” as someone who “has reached the age of 40–by which time a genetic disease known to emerge in childhood should have manifested–but who does not bear the symptoms of disease.” I’m not yet 40, but I’m seriously considering trying to participate in the project nonetheless.

What are your thoughts on the matter? Would you willingly participate given the chance of new treatments or even a cure for PKU? Or does the thought of submitting your DNA have your internal privacy alarms sounding off? Either way, I’d be interested in hearing your thoughts. And if anyone from the PKU medical community is reading this post, please also chime in!


P.S. The 2008 PKU News article referenced above discussed the blood-brain barrier in the context of an emerging therapy called Large Neutral Amino Acids, or LNAAs. The 2014 National PKU Alliance Conference in Salt Lake City July 10-13 includes a session presented by Dr. Eddy A. van der Zee from the University of Groningen who has received a NPKUA research grant to study LNAA Supplementation in PKU Mice.


Filed under Research

5 responses to “Do ‘protective mutations’ hold a cure for PKU?

  1. Anna B.

    VERY interesting and I very much would like to keep a pulse on this. Thanks for posting as this is very beneficial to keep abreast of ongoing research.

  2. Rachel

    Let me first say Thank you for having a social site that is more orientated towards adults. I have been on your mailing list for a couple months now and I great up for the new information you provide.. I have classical PKU and am enrolled in the peg pal study at Tampa General. 35 weeks in no changes in phe level yet but hopeful. I am not the most compliant patient at the low phe diet ever! Which is why I enroll in studies for hopeful outcome . I have switched career paths and able to juggle learning a new field and maintain raising 3 girls as a single mother, my PKU and other health issues. All this with out major PKU problems . Even though my levels remain at a high. I do feel some effects but not crippling of the mind and body. I just keep plugging at it.. I am a firm believer in research and would love to join the fight for better control for us who struggle and those to come. Btw, I am 42 years old and have over come some depression and learning difficulties but find keeping a active brain and body keeps me ” normal”. Thank you again for all your knowledge and research of what’s happening in the PKU world.
    Rachel S

    • Thanks for taking the time to comment and introduce yourself, Rachel. I’m so happy to have you as a follower! It sounds to be – based on what you’ve described – that you might be a good candidate for the Resilience Project. Do you know any of those folks on your medical team at Tampa General are aware of this effort? I would be curious to hear what their take on it was.

      Please continue to keep in touch and come back to comment often!


      • Rachel Schreiner

        Hi Nicole,
        I have a appointment on the 18 th and will be sure to share this with my specialist and the team.
        Dr. Valle Sanchez would be eager to comment in this. She is a fantastic doctor who is making it her mission to help the PKU community live a prosperous life.
        I am eager to learn more about this with hopes of the opportunity to be involved.

        Rachel Schreiner

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s