Year: 2021

As we reach the one month mark of Blaise’s trial, I have certainly learned a lot more about what to expect with being part of a drug trial. I thought I had an idea of what it would be like, but then it actually starts and I’ve learned so much that I hadn’t even considered before! My hope with these blog posts is to not only update everyone on Blaise’s progress with AT-007 (which is VERY important, don’t get me wrong) but also to explain some of my perspective as the parent of a child in a trial. I assume some people reading this blog will be in my shoes someday, if they are not already, and I think it is important to understand it is not all rainbows and butterflies. There are highs and lows, just like any other chapter in life. However, Carl and I believe this is the best thing we can do for Blaise at this point in time, so here is our experience!

So far in the trial, Blaise tolerated the 1 mg/kg dose very well. With the initial dose, (and every subsequent dose escalation, and a safety check 14-21 days after any dose escalation…), we spent a pretty long day at the hospital for blood draws to check pharmacokinetic levels. Some of you might be wondering….”Kara, what the heck are pharmacokinetic levels?!”. This simply means Blaise gets lab draws 4, 8, 12, and 24 hours after a dose is given so we can see what the drug levels in his body are, and see what his exposure to the drug is. On these “long” days, an IV is placed to result in less pokes throughout the day. Blaise is a pretty little guy, but man, he turns into the HULK when trying to draw blood. I am assuming other rare disease parents can relate! I have noticed during this trial so far that Blaise doesn’t mind the needle poke so much as he gets upset about being restrained during the process. I have quite the body contortion routine going on to try and keep him still. I will say there has been one time so far where my mama heart hurt watching him be so sad during a lab draw, and I questioned if this was the right thing. However, Blaise always recovers so quickly and is smiling as soon as you let him go. And I feel like I have to think about the long game, and the potential impact this can have not only on his life, but the lives of others. So we keep calm and carry on!

Back to the good news…Blaise’s labs looked good to dose escalate so we received the green light to move to 5 mg/kg!! Wahoo!!! Now we insert our first “TRUE LIFE: I’m In a Clinical Trial” episode. Blaise started school for the very first time the Monday after he started the trial. Good news is he absolutely LOVES school and went right to his teacher the first day and waved “bye” to me. Unfortunately, as you might expect when entering the petrie dish that is 10+ two year olds playing together, he brought home some kiddie crud. The night before we were supposed to go up to UNC for his dose escalation/increase, he had a fever and was pretty lethargic. *SIGH*. However, as Dr. Jalazo says- “Blaise is a kid, not a robot” and was so kind and understanding. Not only did she check in with us on how he was feeling, but luckily, she was able to reschedule our long dose escalation visit for the following week, so we were still on track!

I need to take a moment for a shout out….I cannot thank Dr. Elizabeth Jalazo enough. She is Blaise’s geneticist at UNC. I call her Superwoman very often (I am running out of Superwoman gifs), and she really is. She has a very unique background in that she did a genetics fellowship because she is a rare disease mama herself, and wanted to become a geneticist to make things better for rare patients. And boy is she! She lives both sides of this life, as the doctor and as a clinical trial mama. Her perspective cannot be beat and she is such a fighter for her patients. She has been such an advocate for Blaise over these past months and I am so blessed she is in our lives!

Okay- back to the trial. Blaise has been on 5 mg/kg dose for over a week now, and all of his follow up labs indicate that the drug at this higher dose still appears to be safe, which is the most important thing! Now we are halfway to what is believed to be the full dose of 10 mg/kg, which hopefully we will be able to increase to within the next month! More to come on that!

It has been a little bit since we had an update on Blaise’s progress (see Grind, Climb, & Landing post for the last “progress note”). He has been working very hard in physical, occupational, and speech therapies. We have gone through several grinds to get to today, but here we are!!

For reference, Blaise is 2.5 years old now. He crawls on all fours as his primary mode of transportation and does not army crawl any more (it took some time to make this full transition). He is also much better with his balance and can catch himself or ease his fall rather than just totally face planting every time if he gets off balance. To date he has split his chin open three times in two places- but it could be more!! He also started to carry things with him when he crawls!

As of mid July, he has a gait trainer. We have been working on his walking independence. He isn’t the best at steering, but at least he isn’t crying the majority of the time when he is in it and seems to enjoy walking and saying hello to people who walk by. We have been to some creative places to get some walking in (Lowe’s Hardware, the grocery store, the splash pad, etc.) but Blaise seems to do his best with a change of scenery! Here is a little insight to his walking!

He can pull to stand, but cannot stand without assistance or something to lean on. We hope getting his legs stronger with walking in the gait trainer will help him work toward standing independently.

As far as speech goes, Blaise’s expressive language is not very strong. For example, Blaise cannot speak in sentences. If he does speak it is one word that is not pronounced very well and you would probably have to understand the context in which he was saying something to be able to understand him. You will probably understand that when watching the videos below. You know what he is saying because Carl or I is translating for you. Here are a few videos of some of his words (don’t mind V’s crying in the background in some of these videos. He was having a hard time not answering all the questions for Blaise instead of letting him respond, so V had to go to his room for a bit…lol):

Blaise’s receptive language is much stronger than his expressive language. He can answer yes or no questions pretty well. This means when we whines or points at something, we usually have to play 20 questions to figure out what he needs, but once we guess the right think he will say “YEAH”. That has been very helpful. Here is some more demonstration of his receptive language:

His intense concentration and occasional misses with high fives and knuckles (knucks :)) leads us to hand/eye coordination and fine motor skills! Blaise still cannot feed himself using utensils, and quite honestly, needs fed for most meals. I do not know if the reason he doesn’t feed himself a full meal is because he is tired, lazy, or bored. But whatever the reason, he still requires significant help when eating to ensure he gets enough nutrition. Here is an attempt at using a fork:

While utensil use leaves a lot to be desired, other aspects of Blaise’s fine motor is doing really well. He is much better at stacking than he used to be!!

Last but not least, here are two videos “for fun” (they are a little longer so I won’t be offended if you skip these!!) showing Blaise get up on the couch and also crawling up the stairs. He isn’t the most steady, but really big improvements from where we have been! While we are so happy he is more mobile, I cannot say I am particularly pleased that he can climb up all of these places to potentially face plant. Yay for heightened mom watch…lol. But all joking aside, we are thrilled with his progress! He is doing things we were not sure if he would ever do. All of these videos were taken the weekend before his clinical trial started, so we hope to see some big moves once we get to a sustained full dose!

Thanks for checking in on Blaise’s progress, more to come!!

I realize it has been quite some time since I posted. But there has been a lot going on in the background, and we are so excited to FINALLY share some really BIG news!

I promise I will post a more formal update on Blaise’s progress since last November. He really has been working hard at therapies and has come a very long way since my last post! BUT, the big news is… BLAISE STARTED AN INVESTIGATIONAL NEW DRUG!!!!

So the back story….we have been in contact with a drug company called Applied Therapeutics since February 2020, shortly after Blaise’s diagnosis. If you recall- my way of coping with the diagnosis was reaching out to family support networks, and Carl’s was digging into the scientific literature to see what the options were available for treatment. So in his research, Carl found an article that a drug class called aldose reductase inhibitors (ARIs) showed improvements in PMM2 in worm and yeast models. (Insert Pharmacist Education Session- how do ARIs theoretically work in PMM2-CDG?! ARIs are thought to increase the PMM2 enzyme activity.) His research then continued and he found Applied Therapeutics, who was utilizing an ARI which they call AT-007 to treat another rare disease called galactosemia. We reached out to the company to inquire if they had any plans to expand their use to PMM2-CDG. I suppose the rest is history.

Fast forward to early 2021, when Applied Therapeutics and Blaise’s geneticist at UNC agreed to take on the challenge of submitting for a single patient compassionate use IND (investigational new drug). For those who do not know this terminology, the FDA will occasionally grant compassionate use IND for patients with a disease or other life threatening condition that has no known treatment or for which all existing treatment options have been exhausted. Consider it the FDA Hail Mary 😉 If the IND is granted, the patient can receive an investigational new drug (sometimes it is FDA approved in another condition, or it might not be FDA approved at all) in a clinical trial type format. However, submitting for this is no easy task- it takes an enormous amount of time and effort to get to actually starting an investigational drug trial.

However, after an incredible amount of hard work and collaboration, ups and downs, we are thrilled to share that Blaise received his first dose of AT-007 last week! He is the first person with PMM2-CDG to receive this drug. Although Blaise received his first dose, we are in a dose escalation phase. We will start at a very low dose and gradually increase over several months to the full dose. This gradual escalation is to ensure there are not liver side effects, as Blaise (like many with PMM2-CDG) presents with some baseline liver abnormalities. So we do not expect therapeutic benefit from the drug for a few more months. Also, both my mama AND pharmacist cup were full when I got to mix the medication and give it to him! Luckily it wasn’t too complicated- just an oral liquid suspension!

We cannot thank Applied Therapeutics and Blaise’s genetic team at UNC enough for all of their collaboration and hard work to make this happen. It has been quite the journey for all! We are also incredibly grateful for all of the prayers and good vibes that we have received from family and friends. Please don’t stop now! We have 12-15 months on this journey. But we are honored and blessed to be a part of this little piece of history. Most importantly, we are very excited to see where this journey leads and opportunities it might create for others with PMM2-CDG and their families. 

If you would like to read more about Applied Therapeutics commitment to PMM2-CDG, click here: https://www.appliedtherapeutics.com/patients…/pmm2-cdg/ (also…there is a patient video posted there with a few folks you might recognize!)

If you have any questions or would like to contact Applied Therapeutics for more information, please email [email protected]