Jonah’s new word.
I said I wasn’t going to write for a while because I’d be too busy. However, I’m still waiting for Columbia Presbyterian’s Internal Review Board (IRB) to come back with the green light so we can start enrolling patients for our IIID observational study! I’m growing more and more impatient as the days pass. Thought I’d take a moment to hit you up for some cash. The 29th is GivingTuesday and the Sanfilippo community is fundraising to help support our programs. https://www.facebook.com/donate/650264436504687/650264453171352/ Here is my fundraiser, if you don’t use Facebook, I applaud you and offer you an alternative way to donate. You can write a check to the Cure Sanfilippo Foundation, write Jonah in the memo line and post to: Cure Sanfilippo Foundation PO Box 6901 Columbia SC 29260
I’m constantly looking for evidence that Jonah is still learning. The other day Jonah and I were playing with his bat cave houses and figures, DC inspired doll houses and action figures. Jeremy and I use this activity to reinforce expressive and receptive communication. The DC characters knock on the bat cave door and greet whoever answers. We ask each other questions about what they’re doing today and encourage Jonah’s figure to ask us questions back. Jonah asked me where Wonder Woman and Harley Quinn were, I told him that they were having pizza at the pizzeria. I asked him how Superman was doing, Jonah responded, “Oh he’s exhausted.”
On one hand I was very proud of Jonah for using a new word on the other I felt super guilty for telling him how exhausted I am all the time. The next day I booked us a trip to the Adirondacks for the long Thanksgiving weekend. It was fabulous, I had the most glorious spa day, I hardly thought about work and completely ignored how much money we spent on treating me. Jeremy and I forced Jonah to go on a hike through the snow and rain and rewarded him with movies and peanut butter Nutella sandwiches. We found him a playground too! I didn’t spend two days cooking; all in all, we had a delightful time. Hope everyone else had a lovely day too.
I worry about Jonah more than usual; I see physical changes, he’s 14, it’s too be expected. I ask myself: has he always tripped in cracks or is this new? How long has he been coughing for? He doesn’t seem to hear half of what I’m saying. Jonah has new orthotics, he’s taken too them well. They slip into his shoes, so no one can see them, they help brace him, so his ankles don’t turn as easily. Jonah’s ankle turns on him frequently when he walks along the seam of the sidewalk or hits a dip or crack along the path. I cringe every time he does it. He yells at me I’m okay I’m okay mom. Writing about it makes me cry. He shouldn’t be tripping in a tiny crack.
He coughs excessively after he eats, which is a sign of a swallowing issue. We finally got him an appointment to see a speech and eating expert to evaluate him. We’re going in tomorrow. I’m hypersensitive of the swallowing issues as our kids predominantly die of aspiration pneumonia. Jonah doesn’t drool which is a good sign. We must get through the evaluation before they schedule the swallow study. I'm super anxious to find out if there is an issue or not.
His hearing has gotten me really worried too. Jonah wears his hearing aides all day at school. I let him take them off before he gets on the bus to come home. At first it was a precaution as to not loose them. If I’m being honest with myself, it’s more of an excuse to not have to fight with him at home to wear them. He constantly asks us what. I say his name when he’s not looking, and he doesn’t respond. He doesn’t hear the door open and shut when I come home. My next goal is to get him a sedated hearing test so we can find out the true extent of his hearing loss. If he can’t hear his ability to learn and comprehend will suffer. I’m wondering if a cochlear implant might be an option for him.
I wanted to add some of these assessments to our IIID observational study, ALL-127. I had to let go of the sedated hearing and eye exam because it was too expensive. My team shot me down on the BARIUM swallow test sighting patient fatigue from all the assessments. Our kids can’t perform the typical hearing assessments, they don’t have the cognitive capabilities to answer the questions. Vision loss is another issue that we can’t assess as our kids can’t sit still long enough to take an image of the retina. I’m looking at the swallowing and gait issues from a neurological standpoint. Sanfilippo syndrome is primarily a syndrome of the Central Nervous System (CNS). The FDA wants to see neurological improvements after treatment. This is extraordinarily hard to deliver on our patient population. It would be easier to do if the syndrome wasn’t so rare. For instance, if we had 20 kids of the same age, speaking the same language and progressing at the same rate we’d have a cohort that was easier to draw conclusions from.
The current way that cognitive function and expressive receptive language is assessed does not work for our, in part non-verbal, multiple languages and severely cognitively impaired population. The assessments used during most trials are not designed for such a diverse group of individuals. Furthermore, the assessments don’t come translated in all the different languages. To have an assessment translated you must first license the assessment, then pay to have someone translate it, then pay again to have the authors of the assessments approve the translations then pay for the certification of the translations to present to the IRB and FDA. Depending on the length of the test, this can easily end up costing $50,000 per language. For our trials we’re using the Leiter-3 which is designed for a non-verbal patient population, so I don’t have to pay to translate it to ten different languages. The drawback is that it won’t capture the receptive/expressive skills and it takes more expertise to administer.
To make up for the lack of standardized assessments available to use on our trials, my team created a protocol of activities of daily living (ADLs) that are to be filmed on a smart phone recording application. The app is called RARE (IIID) and C-RARE (IIIC) Recording Application for Real-world Evidence. The RARE app is hosted on Atom-5 and managed by the company, Aparito. The participants will be consented through our IRB approved protocol by the clinicians conducting the study. When the participants are on boarded, they will be given a code to download the app and a user manual explaining the study and instructions for recording the video tasks. The ADL tasks to be recorded are of the child performing the tasks in real-life under natural circumstances. The RARE app tasks are modeled after the domains of the typically used standardized assessments which are administer to the patient by the physician in a hospital.
This project took a year to design, it is extensive and as clinical as we could make it without disturbing the child’s natural routine. We will capture the expressive/receptive language that the Leiter-3 doesn’t capture during the video tasks. All this will need to be scored by an independent panel of therapists and raters. I already feel like I'll be doing this project for the rest of my life. It's going to be epic!
We’re trying to capture and score the incremental changes of this slowly progressing CNS disorder. The video’s will be done over the same time-points of the child’s clinical visits at the hospital and every 6mo in between the site visits. The study will pick up again after the participant receives drug intervention. The ALL-127 Sanfilippo type D study design has been funded by our NIH/NINDS SBIR grant. It wasn’t a stretch to adapt it for IIIC. We’re now working on designing questionnaires to add to the C-RARE app. The C-RARE app questionnaires, instructions, and caregiver manual will need to be translated to numerous languages and the management of the app, scoring, and data collected still needs funding. However, the cost of creating our study from scratch still doesn’t even begin to compare to having to license and translate the assessments that are typically used for Sanfilippo trials. Fingers crossed it all works!
The mom that inspired me to create Phoenix Nest, Karen Aiach the CEO of Lysogene has released the most comprehensive results of her San A gene therapy trial to date. You can listen and watch the presentation here https://channel.royalcast.com/lysogene/#!/lysogene/20221123_1
It is very reassuring that the treatment has significantly impacted the progression of the syndrome in the little kids, under 30mo. It showed no difference on the primary endpoints for the older kids which is hard for our patient community to hear and accept (including me, Jonah is 14.) The primary endpoints included improvement of the scores of the cognitive assessments BSID-II and the KABS. FYI, once a sponsor decides on a primary endpoint for their phase II/III interventional trial, they can't go back and change it. Once you choose it you're stuck with it and you must show that you improved the endpoint for drug approval. There is a lot of discussion around choosing the 'right' endpoint, but not enough discussion on how to measure that 'right' endpoint.
I'm banking on findings provided by our RARE app and our different choices of clinical assessments to give us a deeper and clearer picture of the incremental improvements of the treated older patients. I believe we will also settle on a better 'right' endpoint and we will have better tools to measure our primary endpoint. With any luck my grammar might improve one day too.
No matter what when our trials are completed and we have concrete evidence that the drug indeed works on the brains of pre-symptomatic children we will have a 'cure' for the next generation of kids. That is something to celebrate and I think Jonah would agree, he loves his friends deeply and hates to see anyone in distress. We have the sweetest kid ever, see for yourself.
As always thanks so much for your continued support and Happy Holidays!
.jpg)
To Donate go here:
