We thought it was about time to give a full update of what we are seeing in the clinical trial, so here goes….
First and foremost, Case is healthy and doing very well physically and medically. That is the most important thing to us given that there are so many unknowns in a clinical trial of both a humanly untested drug and device.
Case has shown significant improvements cognitively. As background, here is what you may need to understand about where he was cognitively prior to the trial. In February of 2010, Case tested too high for the trial criteria.
His language was quite broad for a Hunter boy and he was able to say things like “Thank you for coming to my treatment!” However, at that time he was still developmentally delayed and his behaviors were increasing such that it was getting clear that he had the severe form of Hunter Syndrome and would start to lose cognition at some point. My guess in retrospect is that around July/August of 2010 (around 3 1/2 years old), Case started to lose cognitive skills. Here is a video in August 2010, where he could maintain attention to sing an entire song and seemed very engaged.
Contrast that with a conversation from several months later where you can see that he has difficulty staying on track, having an engaged conversation, and keeping attention to sing a whole song.
Because you see him every day, you don’t realize that things are disappearing until you are faced with proof. In October of 2010, we returned to UNC for repeat cognitive testing. I was in the room with Case and to me, I thought he did quite well. Clearly I am no neuropsychologist. The testing showed a loss of 18 points since February’s testing (points of what, you may ask… for us adults it would be IQ points, but at this young age, they are referred to as general cognitive index scoring). It was only then that we realized he was no longer saying these long sentences, it took him longer to process things, had more difficulty remembering. Almost within the week of the testing, he began to stutter and it increased over time. Sometimes he just gave up on what he was trying to say.
One also needs to understand that cognitive testing for children involves norms that are relative. So, a child’s abilities are gauged against what he should be able to do and understand for his age group. Case both lost some cognitive abilities and was unable to improve or keep up with the learning growth of other children his age.
So that brings us to the improvements we’ve seen. Cognitively, he seems to be at an overall (not normed for his age) level higher than he has ever been. His receptive and expressive language are clearly more than he’s ever had. I started writing things down after the first dose, but by the second one, there was almost no point in keeping track of the details anymore. Some of the first things I wrote down were “Mommy, come on down!” (Wasn’t sure if they were watching The Price is Right during the infusion or what?) and “Be careful!” He started playing with his toys in incredibly normal ways, having the people talk to each other, etc. This was one of the first videos I took that showed these clear changes – it was from about 2 weeks after the first dose.
The night after the first dose, he sang the entire Barney song all the way through. If you saw the video of our conversation before the IT trial (2nd video above), you can see that he could not hold his attention together long enough to sing any whole song at the end of the video, much less the Barney song, as much as he likes it. He also had an entire conversation with Chris (his daddy) 2 nights after the first dose. He asked and answered questions – he was entirely unable to stay on track and understand that before the trial.
Now he asks questions like, “Mommy, do you want to come play with me?” He says he loves me and wants to hug and kiss me (of course, my favorite!). He understands when his brothers are doing something and he isn’t and he wants to! He now takes his dishes to the sink after meals and other “chores.” His receptive language has improved so that he understands things that I tell him so much more. He will now complete many 2-step tasks, understands and uses before/after, uses any, sequential lists, and sequential sentences. He is more aware of the people around him and how his actions affect them. Before the trial, in a play setting, he would run into and over other kids, climb on people’s tables, eat their food, etc. without any real understanding of the effect. Now, he allows other children in front of him in line for the slide (!), and has a sense of what is appropriate behavior. I can actually sit down at a McDonald’s play area instead of following him everywhere! He even understands time-outs again (unfortunately, with the strong-willed behavior and essentially the cognition of a 2 1/2 year old, he gets many of them!)
He still does not understand the use of “why” so I sometimes use markers like that to test where he is improving.
Although Case has improved cognitively, he is still showing deficits in his learning style. This is an area of total unknowns. Even if Case stabilizes or improves cognitively, it does not necessarily make his brain a “typical” brain that learns and retains like another child. He has shown that he still takes a significant amount of effort and repetition to learn and retain new information and skills. For example, his ability to count to 10 comes and goes. Sometimes he can do it well and others it is 1, 11, 8, 9, 10. You see what I mean.
Case’s behaviors from his condition have improved. As background, he had what looked like significant ADHD, some autistic behaviors (perseveration, scripting, limited interests, need to follow a particular schedule), lack of a sense of danger, deficits in proprioception, and a marked lack of impulse control. Case is much calmer and has a noticeably longer attention span (although those who did not know him before would still consider him pretty hyper and with a limited attention span compared to a typical child). His autistic-like behaviors have lessened some – we no longer use a daily schedule, he does not throw a fit if we turn the “wrong” way, and his interests in toys and movies are somewhat broader (although as I type this, he is watching the Wizard of Oz for the millionth time).
He still has compulsions that are hard to control like hitting buttons, picking up phones, etc., but improvements are there. His sense of danger has not really improved only because he thinks he can do more (and can) and so we give him more freedom – thus resulting in more risk. For example, he thinks he can hop from one step to the next and then falls down several steps. His proprioception deficits have improved somewhat – he does not run EVERYWHERE as much anymore or lead with his chest all the time. He still has a need to climb and push and pull heavy objects, but that is manageable. His impulse control has noticeable improved. For example, he would sweep and grab things off shelves, open and close doors repeatedly, hit his brothers (hard), etc. He can now control some of these impulses on his own and even better with reminding him (using direct, close eye contact). For example, I was able to bring him (in his stroller chair) into Sephora! For all you men, that is a cosmetics store with many things setting on shelves in close proximity to his reach. With reminding, he only grabbed for things 4-5 times, when I wouldn’t have even considered taking him in a store like that before (or I would have had to leave my checkbook). We are able move from room to room in our house some of the time without constantly closing baby gates to keep him from hurting himself, getting things he shouldn’t, escaping, or creating total chaos.
Since the trial started, Case has physically changed in certain ways that are difficult to describe. Several people have mentioned that his posture has improved – he is standing more erect. I totally agree. I have racked my brain to figure out what the precise difference is, but without an exact comparison picture of before/after, that is difficult to do. I’ve tried to put together some pictures that might display what I’m talking about, so please comment if you notice something I’m missing.
It does seem that his neck has lengthened (these boys generally have little to no neck), his body has lengthened, and he seems to be more proportionate. I wish I had more precise pictures. Also, physically, he is just steadier with his body and limbs. He can now drink from an open cup without spilling most of the time as well.
Case is pretty close to being POTTY TRAINED! Although he has been working on preliminary steps for awhile under his IEP, it was clear that without this trial, he likely never would have been potty trained. But after 2 doses, the school asked us to just put him in underpants for school a week before the 3rd dose (BRAVE people). He has been doing great! He does have accidents here and there, usually when he is outside or doing something fun that he doesn’t want to stop and tell us he has to go to the bathroom. But he actually tells us usually that he has to go! And, he is generally dry in the morning and after naptime as well (even though we put him in a diaper still). He flew on the plane last month in underpants, which was a little stressful to me (especially when we crammed into the bathroom on the plane for an uneventful try), but he was fine.
Finally, Case just becomes more typical everyday. He just talks, walks, acts, interacts, and becomes more like my other boys every day. It was a big jump at first but the changes are now more difficult to describe. Slowly, I’ve started to be able to discern certain characteristics that are part of his personality, not MPS. For example, I’m discovering that he is a strong-willed child, like my oldest. It was always difficult to tell what were just MPS quirks, stubbornness, impulse control, and perseveration, and what was Case. If you’ve missed the last several posts, you can see more about what he is like now when he’s playing at recreation therapy and when he’s getting his Elaprase (not IT) infusion.
So if you’ve made it to the end, I’ll reward your diligence with some hard evidence! I had known and documented all the improvements I mentioned, but Case recently had cognitive testing after 3 doses of the new drug. I was concerned that it might not validate the improvements we were seeing because the cognitive testing is both difficult to perform on our boys and does not always accurately capture all they can do because of behavioral issues like attention span and perseveration. With that being said, Case’s general cognitive index (or you can call it his IQ) improved from the baseline established immediately prior to the first dose by … 10 points. 10 POINTS!!!!
Another boy in the trial is entering regular kindergarten in the fall. Regular kindergarten. Even with supports, this is an amazing fact. I have to be honest, no one was expecting that our boys would have an opportunity to stabilize, much less improve, really within their lifetime. This is entirely a miracle, I believe. God has shown his grace and mercy to us as He did to Hezekiah. In 2 Kings 20:5, King Hezekiah was told that he would die. He pleaded with God and it says that he “wept bitterly.” God responded:
I have heard your prayer, I have seen your tears; surely I will heal you. On the third day you shall go up to the house of the LORD. And I will add to your days fifteen years. I will deliver you and this city from the hand of the king of Assyria; and I will defend this city for My own sake, and for the sake of My servant David.
I don’t pretend to understand God’s ways – why he would give us this miracle, but then I see other children suffer and even die. I don’t see the big picture. But, I am incredibly glad that God does. Even as the healing is occurring, I still remind myself that we are all dying. Thankfully, Case may not be taken from us at the early age of 12 or 15 because of the cognitive decline caused by Hunter Syndrome, but he just as easily could be taken by some other means, as mothers, fathers, brothers, and sisters are unfortunately taken from their loved ones each day. So while I rejoice in the miracle, I am reminded as to why we are put on this earth – to love the Lord with all your heart and to love your neighbor as yourself. Matt 22:36-40. I hope and pray that as we walk through these challenges, that we are fulfilling God’s calling on our lives in this way.