The Magic Sentence

As you read this, I've just gotten home to Maine. I went to Huntington Beach, California, just a few miles south of LA. I went to a rare patient advocacy summit, put on Global Genes. Why did I do this? Because I have a new job. One that doesn't pay me anything, but takes a ton of time and energy and organizational skills. My wife took on the same job, at the same time. On top of her full-time job.  

Seriously, pretty much every night these days, after dinner she and I coax the kids into bed. We shake off the evening weariness, the yearning to binge-watch a delightfully mindless season of a TV show, and put on a pot of tea. And we get to work. 

Now, I'm as puzzled as you. All this time, all thirty-seven episodes of the podcast, all I-don't-even-know-how-many blog posts over the past months and years, in the back of my mind I guess I assumed that our goal was to find other kids like Tess. And bonus if we could actually find any doctors who were addressing whatever the deal was with those kids. Here we are, checking off both of those boxes. Seven other kids like Tess, maybe even more. And yep, a genetics team at Baylor College of Medicine in Texas. We didn't have to convince the Baylor crew to take on Tess's disease. They were already doing it. They moved their chairs aside, made some room, and invited Tess to have a seat at the USP7 table, where they promised to do all they can for her and us. 

So we've made it, right? Well, no. We have work to do. Lots of work. Much of this work has to do with a single sentence in the paper that the Baylor team just put out there. This was the magic sentence:  "Finally, our results suggest that chemically activating WASH in these patients may have therapeutic potential."

WASH is a protein. And USP7, Tess's mutated gene, controls how much WASH activity there is. So in other words, the paper says that if your USP7 gene--the controller--doesn't work, there's maybe something you can do. You can chemically activate WASH in Tess. Through medication. Or gene therapy. Or who knows what.

It gets better. We had a skype call with the head researcher at Baylor who's working on this stuff. He's a German guy named Christian Schaaf. Young guy, maybe mid-30s. Before we hopped on the video call with him, I was expecting him to be reserved. Tight-lipped. Prone to laying down science-y qualifiers, like "Given what we've observed in the lab, it's unknown whether these particular deficits can be addressed in a therapeutic setting." In spite of that sentence that was in the paper. But he was quite the opposite. Cheery. Talkative. A twinkle in his eye. In a photo in a recent profile in the Houston Chronicle, he's letting a baby grip his finger, and he's got rosy cheeks and a wide smile that would rival Santa Claus. Not the sort of guy you'd expect to spend hours in labs. And he said to us, "Now I hesitate to even tell you what I'm about to tell you. I don't want to generate false hope. But I do think there's reason for hope. And that's because in another study, having to do with another gene called MAGEL2, they found that in mice, some brain deficits were able to be restored." In other words, Dr. Schaaf was telling us that maybe--maybe maybe--whatever was up with Tess' brain as a result of her USP7 mutation wasn't necessarily irreversible. Those mice in that other study did better after the deficits in their brains were addressed. They got better. Yes. Yes. Awesome.   

Dr. Schaaf oughta know about MAGEL2. He's done a ton of work on it, and even published a paper about it. The way he explained it, there are three genes he's focusing on. USP7, which is Tess's gene. MAGEL2, the one with the mice study. And another one called TRIM27. He hasn't solved every single piece of the puzzle yet, but he's fairly convinced that they're all connected and related, that if you take one away the whole complex falls apart. 

And what he told us is that there's a spectrum of disease, going from the ultra-rare (Tess and the other USP7 kids), to the not-as-rare (Prader-Willi syndrome, which occurs in 1 in 15,000 births. Prader-Willi is a disease you may have heard of. It's marked by, among other things, obesity and sleep-wake cycle disturbances. It's the one where in childhood, those affected develop an insatiable appetite, one that prevents them from realizing when they're full and don't need to eat any more. 

Again, Dr. Schaaf hasn't nailed down this entire theory, but he's pretty sure that USP7 issues land Tess sort of in the family of Prader-Willi, since MAGEL2 has implications in Prader-Willi and the USP7 symptoms have some similarities to both Prader-Willi and MAGEL2 genetic issues. A sister disease to Prader-Willi is Angelman Syndrome, which seems slightly more common--1 in 10,000, according to one study. 

Why am I telling you this? Because research and drug trials and activating the WASH protein in my daughter are, like many things in this world, about money. And if you think about it, is Dr. Schaaf likely to get funding to help a total of eight kids on this planet? Or is it more likely that he'll get funded to work on stuff like Prader-Willi and Angelman syndrome? 

Schaaf gave us some homework. And that's why I headed to California. And why my wife and I get down to business instead of watching TV every night. My wife's job is to push forward on the medical side. Tess stands apart from the other seven USP7 kids. It hasn't yet been proven that the USP7 mutation is the cause of her disease. Right now, technically, that mutation has what's called unknown significance. Is it the cause? Yeah, probably. She looks a lot like those other kids on paper, with most of the same symptoms. But it hasn't been proven. That happens in a lab, with cells. It takes time. And most important, it requires a skin sample from Tess. Luckily, there's one sitting in Boston, in liquid nitrogen. They kept it at Boston Children's Hospital after her hip surgery a couple years back. And Kate's big job right now is to get that skin sample out of Boston and into Texas, so they can test it. 

My job is PR. I need to keep getting the word out. We think there are other kids with USP7 mutations. I want to find them and get them into the next study with Dr. Schaaf. The more patients we have, the better. More patients means more attention, which could mean more funding. Yes, we see USP7 on the same spectrum with Prader-Willi, but we still need more USP7 patients. 

These are our new jobs. On top of the ones we're already doing. We are advocates. We thought we were advocates before, bringing the heat when it came time for Tess's IEP. But now the game has changed. The stakes are higher. We want to move fast. If we need to start a foundation, to get funding, to get drug trials underway, to do any of this stuff that we and Dr. Schaaf have in mind, we want to do it soon. Every day that goes by is a day that maybe we could've helped Tess and we didn't.