Busting…I’m busting! Its been almost 8 months since we sat down with our Geneticist at Children’s Hospital Colorado and were told that Whole Genome Sequencing (the most extensive genetic test available) discovered a gene that looked promising, PRKRIR. This was such exciting news, but came with the disappointing caveat that we were the only known people IN THE WORLD to suffer from a condition related to this gene, so we couldn’t really be sure it was the culprit. At first it seemed like all there was to do was wait…but waiting isn’t in my nature and over the past 8 months we have managed to make some huge strides that keep me up at night with excitement and hope.
One big development came from the Rare Genome Project out of the Broad Institute at MIT. I found this research study before Abby was even born, and they were in the process of Sequencing our family’s DNA when Abby was diagnosed. We immediately informed them that we had a second child with the same condition and submitted her blood to be added to the analysis. I talked to them shortly after our genetics appointment at Children’s. At this point they had completed their own independent sequencing of our DNA. I remember the genetic counselor telling me that they were highly suspicious of one particular gene, but since it was a hunch (granted a very confident hunch) they weren’t able to give me the name of the gene. I pitched a compromise to her…what if I already knew the gene and told her the name, would she be able to confirm if they are looking at the same one as Children’s Hospital? She agreed and I got a reassuring “yep!” when I said PRKRIR. Eeeekk!! For me this was huge! It meant that two separate entities doing their own method of genome sequencing came to the same conclusion. It was a much needed level of reassurance in this gene, and has given me the confidence to focus solely on proving this gene, rather than searching for other possibilities. I believe we have the diagnosis (and the docs do too)…now we just have to prove it.
This takes me to my next update…About 6 months ago we braved airplane travel with both girls and all their gear and traveled to Stanford University in California to become patients of the National Institute of Health’s Undiagnosed Disease Network. Along side the Rare Genome Project, this research network is the Gold Standard. I applied when Abby was first diagnosed and finally, after a decent amount of pestering, they looked at our application and accepted us. We made our trip to visit them in person and while there the girls gave blood samples, skin biopsy samples (they can use this to grow stem cells if needed), and we detailed their full medical history. The doctor even noticed how both girls have the same unique-ish shaped ears! Well fast forward to yesterday when I finally (after a bit more pestering) was given the news I had been waiting for! Animal Modeling! The Undiagnosed Disease Network has a ton of resources, including two teams that model genetics in animals. Yesterday they told us that they will start the application process to submit our case to the animal modeling core. If they accept, which docs believe they will because our case is pretty interesting, over the next year or so we may see little Emma and Abby versions of worms, or fruit flies, or fish, or if we are lucky…mice! Since we don’t have any other families to compare to, this is our only way to prove this gene is the cause of our family’s disease. If the animals have seizures, we can be confident that our broken gene is causing them. We could finally have an official diagnosis instead of floating around in a sea of symptoms of an unknown origin.
But why does it matter? What changes by being able to put a name to a disease? Well…Diagnosis is the first step towards treatment. In 2018, a little girl here in Colorado was dying of a fatal genetic condition called Batten’s disease. She became the first person to have a custom drug developed only for her based on her genetics, and so far it has stopped the progression of her disease and is saving her life. The drug is a kind of genetic treatment called Antisense Oligonucleotides Therapy (or ASO for short). I’ve done my Google/YouTube research on how this treatment works, but its pretty over my head so I won’t try to explain my rudimentary understanding of it here. But the point is….its a therapy that can target a specific genetic “mess-up” and trick the gene into working correctly again in the body. For this little girl, its a life-saving miracle. And for the rest of the rare community, its an icon of hope. She pushed open an extremely heavy door to possibilities for families like ours. Ever since catching up on her story, I have dreamed of finding a researcher that will take on our case to develop a custom ASO for the girls. Then one evening….as I’m sitting listening to one of my many genetics podcasts, it was as if someone read my mind. A brand new foundation had been created who’s mission is, and I quote, “to apply the efficiency, versatility and specificity of antisense technology to charitably provide experimental antisense oligonucleotides (ASO) medicines to treat patients with ultra-rare diseases (<10 patients)”. To translate…they want to donate, as charity, custom genetic treatments for people whose disease is “ultra-rare”, meaning it only affects 10 or less people in the world. That is us! My heart skipped a beat as I was listening to this podcast. Someone had to have hacked into my brain, I was listening to my dream coming to life. I’m not sure I slept that night, my mind was spinning with hope. This genetic journey has been a mixture of obsessive research paired with some pretty good luck. And learning about this opportunity gave clarity to the path I’ve been trying to forge. It gave me an end-goal, something to work towards. It gave me a realistic possibility for treatment!
Don’t get me wrong though….while this is an amazing opportunity that fills me with hope, I’m cautiously pragmatic in how far we still have to go. First we have to get that darn diagnosis…the animals have to seize, the gene has to be proven. Then we have to apply to this program, and they could deny us for a million different reasons. Our gene may not even function in a way that this treatment would work. BUT….it could also all work out and be our dream come true. I have to try my hardest no matter what the outcome. It will never be a home run, our girls are too far progressed into their disease to be totally cured. But with genetic technology moving as fast as it is, I am confident we will be able to find a treatment that will give them a better quality of life. Maybe someday they can live seizure free. And in the meantime, we are hopefully helping pave the way of genetic science for families in the future.
So I apologize for being MIA for the past three months…As you probably figured after my last post, we made it out of the hospital. We got to go home the day after Thanksgiving and were able to have a wonderful Christmas and New Years. And since then we have kind of just been living…we stay pretty hunkered down in the winter months and enjoy lots of couch snuggles and HBO binges. We have an exciting year ahead of us with hopefully more genetic progress, a couple genetic conferences, a long-awaited couples vacation to CROATIA (please go away, Corona-Virus), a 60th birthday celebration in Cancun for my mom, and a few other little tidbits that we’re working on.
Sending so much love from Colorado, and hope everyone is having an amazing 2020 so far!