In Pursuit of a Treatment

It has been about 10 months since we learned about the underlying cause of Emmett’s condition.

I’ve talked a lot about what has gone on with him from a day-to-day perspective, but from January, we’ve also worked on understanding and researching his disorder to see if there’s any hope of improving his underlying disorder. Getting any sort of information and traction seemed so far-fetched when we first started, but I’m very excited about all the progress that we’ve made until now. (This is due in very large part to the help we’ve gotten from Steve’s friend Andrew, who I mentioned in a prior post. His background is in the pharmaceutical and biotech industry.) And I wanted to share our path, if for nothing else than because we’ve spent countless hours and put so much hope into it. Also, on the off chance that someone reading this might be able to either benefit or help with our next steps (mentioned at the end of the story), we’d be very grateful.

Coming Up With a Plan

It all started with a presentation Andrew put together based on research he did about where the PIGA gene is located and the function of that gene. First, some facts:

• The PIGA gene is involved in a process called glycosylation [which is why it falls under the Congenital Disorder of Glycosylation (CDG) grouping]. Broadly speaking, Emmett has a CDG. And even using that broad label, there are only about 2,000 people worldwide diagnosed with a CDG, showing just how rare it is. (In the U.S., a rare disease is defined as one that affects fewer than 200,000 people.)
• Glycosylation is a super important process to building a person, which is why Emmett’s mutation impacts almost every function in his body and mind.
• The PIGA gene is the first gene involved in a very specific kind of glycosylation… it helps to make GPI anchors, which is involved in a lot of different biological processes. So PIGA falls under the GPI anchor pathway category.

Knowing that Emmett’s gene is defective, Andrew came up with three approaches we might want to consider:

• Increasing the sugar that goes into his GPI anchor pathway (aka GlcNAc). It’s a supplement that’s available over the counter.
• Increasing the PIGA protein itself (through something called NAC). This is also a supplement that exists and can be purchased.
• Increasing what his pathway produces (aka GlcNAc-PI). This supplement doesn’t exist in a form that can be given. More to come later.

Here’s a graphic version of those approaches:

These three approaches, based on his research, seemed to have the most scientifically sound rationale for trying. Our next task? Getting doctors to review the document to let us know if it had a snowball’s chance in hell of working.

Vetting the Plan

We spent the better part of the next half year showing and sending it to every neurologist, biochemical geneticist and CDG expert we could find, and we reached out to some of the doctors that had authored past PIGA-related papers. When we got in touch with one doctor, we asked if they knew any others we should talk to. And so on and so forth.

All the feedback we got were along the lines of, “These are really interesting ideas, and in theory, they should work. But you also don’t know how these sugars – which impact many different pathways – will affect his body.” No doctor felt comfortable advocating for these treatments, but the silver lining was that they seemed to think there was promise in exploring these treatments. The last approach seems to hold the most promise, but this is more the long game since it would take much more work to find someone to create a viable supplement.

In parallel, we cycled through the next “standard” treatments our doctors suggested – pyridoxine this spring, the keto diet in the summer, then Felbamate this fall – none which worked – all the while getting expert opinions on Andrew’s presentation. The three of us cold-emailed and got referrals to anyone who might have insight to offer. And through those connections, Andrew got in touch with a professor and doctor in Osaka, Japan, who actually worked with the patient I’d mentioned in an earlier post who had the same variant as Emmett. And here was our first big break. He agreed to do in vitro (in lab) testing on our approaches, provided we could come up with the funding for his tests. It would take six to nine months to develop a cell line with the mutation and to introduce the supplements.

Creating a New Compound

Our next obstacle to tackle was the development of GlcNAc-PI (Approach 3), which is what PIGA helps to produce. And with that development comes questions about how to structure the compound and how to make it in a way that it would cross the cell membrane and blood-brain barrier and go where it needs to go. (I’ll admit, it’s over my head, but I just know it would take an expert in biochemistry and maybe even glycosylation to tackle these complexities as they develop the compound.)

Now for the next big break (out of 20 smaller breaks it took to get here). There is an individual in Germany (who heads a lab and is a carbohydrate chemist) Andrew got in touch with who seems willing to work with us to develop GlcNAc-PI. (When Steve and I heard this, we were beeeeyond ecstatic.)

Now What?

This happened a week ago. And so here we are. Lots of work to do. Lots of questions to answer. (Believe it or not, that was the short version. But if you want the movie version, you should check out Harrison Ford’s Extraordinary Measures, a movie about parents who team up with a glycobiology researcher to save the lives of their children. It’s no Indiana Jones, but we thought it was interesting.)

What We Need Help With

Right now, our main goals are to find contacts in the pharmaceutical industry (or FDA’s regulatory area that cover lab testing) to figure out how to fast-track review for the GlcNAc-PI that gets produced. (We think we might be able to use the FDA’s Expanded Access path to get approval which would, in theory, shorten approval times from years to possibly months.) Learn about the nonprofit/foundation world so we can figure out how to fund the needed research. Get Emmett the physical, occupational, vision, speech and stimulation therapies he needs. Keep him out of the hospital. (And here’s my plea for help. If there’s anyone who can help with those first two, please let me know!!)

Also, I mentioned that we were going to try cbd oil next, and that’s still the plan. But we got word that there is a cbd trial starting up again at UCLA so we’re waiting to see if we can enroll in the trial. Again, there are a number of factors impacting that decision – like whether we can try our approaches one and two while on the trial – but we’re on hold till we find out more. 😊

As Thanksgiving rolls around this week, I’m grateful for all the good in our lives. Andrew, for all the work he’s put into helping Emmett. (He has his own little one now, and since being a first-time dad is no easy feat, we’re amazed he still has the time to help us with the research.) All the doctors and researchers for their time in reviewing the presentation, offering us their feedback and connecting us to others who can help. His medical team (doctors, nurses and therapists) for making sure he’s okay on a day-to-day basis. The parents of other special needs children who we read about and connect with (mostly on social media but once in awhile in person) who give us hope and share kind words and such inspiring stories. The family and friends around us who make time to say hello or hang out and who offer help, info and food. And so many more.

Even if our miracle treatment comes to fruition, we know that there is a steep mountain to climb and that he will have life-long challenges. But after multiple doctors telling us that we may want to focus on his comfort versus trying to treat him, to think about palliative care and medical facilities for the future (well intentioned, I understand), or even medical professionals not feeling any urgency with his case because there likely is nothing we can do, the potential it presents for him and others in his situation gives us some hope.

Anyway, that’s where we are in a (long) nutshell. Happy Thanksgiving everyone! Please hug your babies extra tight this holiday season for us. And thank you for the continued support. ❤

-Ann