Cyclone

 

Coney Islands infamous Cyclone roller-coaster doesn’t hold a candle to my life. My life is so scary... How scary is it you ask?  It's so scary that I recently threw-up in my Dutch Bros cup.

 

Jonah attends school year-round. He has a small break at the end of summer before school starts up again.  I was torn between going to Oregon so he could have some family time or staying home so I could work. Jonah’s break coincides with one of the NIH/NINDS grant funding rounds. I had PTSD just thinking about being in Oregon last summer when our current grant was funded.

 

These grants are our community’s lifeline, I need to be able to drop everything to respond to an NIH/NINDS grant inquiry. The federal government takes them just as seriously. When you’re notified that your grant has been ‘recommended’ for funding you’re requested to submit numerous supporting documents. The process is called Just in Time (JIT), half of the supporting docs are regarding company financials. It’s basically like taking out a mortgage and closing on a house. The other half of the JIT articles relate to your grant’s specific aims.  You’re given a deadline to get everything in, if you miss it, you miss the funding round, hence the acronym JIT.  Last year’s grant included human participants, which involved getting certifications completed for JIT. It was intense and being 3 hours behind the east coast makes everything just a little bit harder. I knew if I went home this September that I could be in double trouble, but I went anyways.

 

Double trouble, we have potential funding coming in and we’re resubmitting the same grant just in case we don’t get awarded this time. Back story last spring, we won a grant, but funding was ‘deferred’. We received a great score, what they call an awardable score, but due to budget cuts only the perfect and near perfect scores got funded. Deferment meant that if another awardee did not make a milestone, then PN could get their funds. By September 5^th we’d find out if somebody missed their milestones so that our ‘deferred’ grant could be awarded. September 5^th was also the deadline for re-submission. Our program director told us to be prepared for both case scenarios.

 

PN’s Scientific Director, Sri does the grant writing, my job is to create the budget and gather the letters of support (LOS). It’s me that presses the submit button, so I need to be next to my computer and ready to trouble shoot error messages. I’ll tell you about error messages another day. I booked our tickets to Oregon and spent the next three days pulling together all the JIT articles that I knew they’d ask for and at the same time asked our collaborators for updated LOS. An outdated LOS or quote can give you bad marks on a submission and ultimately cost you the grant. Meanwhile Sri worked on updating quotes and adding in the new data. The second day into our trip to OR we received the letter acknowledging that our deferred grant had now been recommended for funding! JIT requests started coming in. At this point you’re still being warned not to get too excited, it’s not a done deal until the notice of award (NOA) is sent out.

 

One of the JIT requests questioned our use of a foreign research organization to manufacture our vector. The NINDS gave us 3 options the first was to find a US based manufacturer.  This is not something that can be done in a few days. The thought of even trying to make this happen was staggering. The wait times for vector manufacturing can be over a year, the work involved is extraordinarily detailed, it costs millions of dollars. Manufacturers need to have the blueprints to our construct; they must have internal meetings to discuss if their facilities can even do the work. The second option was to pay for the vector out of our own pocket, moot point. The third option was to submit a justification as to why we had to use the foreign component. I thought we had sufficiently justified the need for the foreign manufacturer in the body of our grant. If the reviewers didn’t think that justification was good enough, then what else could we say to them now?!

 

I talked to Sri first thing in the morning, he assured me that we had good justification, he reiterated our stance in a letter to NINDS and we submitted to JIT. The next question from NINDS was for the credentials of the foreign manufacturer, which is Viralgen by the way, they’re located in Spain.  Our grant program director said that funds going to Spain had to be approved by the State Department. Who says that? Well, who says that to little ole’ me anyways? I must get it approved by the State Department. Ha! She also informed us that approval could take a while. I thought to myself, no way we’re getting approval in time; good thing we re-submitted.

 

This was now the fourth time we submitted our gene therapy grant (JLK-247) for San C. The second time we submitted the grant it was kicked back due to ‘overstuffing’.  Overstuffing... we had included FDA comments that the grant submission portal ‘gatekeeper’ (for the lack of a better title) said to be against grant rules. Our justification for doing this was because the first time we submitted the grant and didn't win, the reviewers commented that they’d like to see if the study design had FDA buy-in (I’m paraphrasing). We went to the FDA, received the nod, and included their comments regarding our study design to the grant as a letter of support and resubmitted. The gatekeeper did not like that approach and accused us of trying to get around the grant page limit by adding in FDA comments as a LOS. For the record we also added the comments in the body of the grant. We included the official comments as a LOS because we thought it was a nice touch and our program director agreed.

 

Sri and I fought for the grant to be permitted through and asked to let us go with a warning. She could have redacted the portion of the FDA comments that she felt were unfair (I'm pretty sure she actually used the word egregious) to the other applicants. It was a heated conversation. The gatekeeper demanded that I put in writing my justification as to why I was so special that I got to cheat (I’m not paraphrasing). At this point I was foaming at the mouth.  I have a consultant that advises us on grant submissions, he highly recommended that I drop it, that I was not going to win this argument. I let it go and we resubmitted four months later at the following submission date; this is the grant that got deferred.

 

Not that we have come full circle, did we win the grant or not?  I don’t know, I do know that the State Department approved our justification to working with Viralgen!  I’m thrilled but trying to temper my expectations. I think we’re just waiting on the OLAW (Animal Welfare Assurance) confirmation now; we sent it in on Thursday but no response if it was enough. Radio silence.

 

There have been a handful of diagnosed San C patients this year. It’s always how long how long how long. I respond I don’t know, it’s not up to me. That doesn’t stop them from asking. I don’t blame them; I know exactly how they feel. What brings me to tears is the overwhelming feeling of helplessness, drug development does not come with a GPS! I'm trying to go as fast as I can families.

 

The grant funds will cover the study that analyzes the tissue from the mouse dosage study using our new vector (JLK-247) this study was supported in part by the Cure Sanfilippo Foundation. Among other things we will be looking at the biodistribution of JLK-247. If it and everything else is good, then we can go to the FDA and ask if we can go to trial. If they’re not convinced, we’ll have to do another animal study.

 

It has been an extraordinarily busy year. The grant that was awarded this time last year is funding for the Natural History Study (NHS) protocol design and implementation of Sanfilippo syndrome type D, the program name is ALL-127. I’ll spare you the gory details of securing that funding and skip to the exciting part. Writing a clinical protocol 101: Patient input matters more than most sponsors imagine. The FDA talks about how important patient engagement is for selecting endpoints and trial design every chance they get. I’m not getting the sense that sponsors have really understood or taken to heart that message. They can’t just send out a survey asking families what the biggest burdens are. That isn’t good enough.

 

Patients need a seat at the table, not just metaphorically but literally. We need to have a say in how the symptoms are measured. Some symptoms (endpoints) are easy to measure- straight forward. In the case of Sanfilippo there is not one endpoint that is straight forward or easy to measure. Which is mind-blowing because the syndrome affects every system of the body. It hits the central nervous system (CNS) the hardest, a hit to the CNS radiates out to the all the other bodily systems.  Affecting the way our kids: walk, talk, eat, think, sleep pee/poop, process sensory input and behave. The children’s other organs are affected as well but the impacts are subtle and don’t cause immanent death. Unless their lungs fill with fluid from pneumonia, which doesn't make for a good endpoint either.

 

For the Sanfilippo community communication and mobility are two of the top-ranking symptoms. Improvement in communication gets lost in translation to sponsors. We can’t just say improvement in communication to a sponsor. The sponsors think speech. A parent of a Sanfilippo child sets the communication bar much lower. We want our kids to be able to communicate non-verbally, it can be as simple as a smile. A smile from our kids means everything to us. Think about it, what if your loved one stopped smiling? Will the FDA approve a million-dollar drug for smiles? A million-dollar smile, totally worth it 😊.  

 

In the case of Sanfilippo, sponsors have leaned on cognitive tests for measurement of treatment improvement, think of the SAT. These types of assessments are guarded by the authors and license holders. To see them you must have your clinical team lined up and prove your intent of conducting a clinical trial. When we first wrote the grant, we had to include a synopsis of our intended clinical protocol for ALL-127. We chose assessments that were used in the other clinical trials for San A and B. At this point I had still not gained access to the cognitive assessments. It wasn’t until after the grant was awarded and our site and clinicians had been secured that I was permitted to see the assessments. By then we had finalized our protocol and sent it in for IRB approval, this was no small feat. 

 

After reviewing the assessments well if you can’t guess by now… I was nauseous and plagued with doubts.  The assessments in my opinion were not appropriate for the Sanfilippo patient population. At the same time, our FDA comments came back, they had reviewed our protocol and had numerous suggestions regarding out choice of cognitive assessments. The final straw was the results from the failed and divested San A and B drug trials that were finally being published. The data suggested further that the chosen cognitive assessments were not appropriate to measure their endpoints. Our ALL-127 protocol had literally just received IRB approval; we could start recruiting patients soon. We were faced with a major decision- continue with the status quo or start over. We started over. Now we were faced with missing a milestone and not  having funds released in time to continue study startup. It’s a non-stop roller-coaster ride. I can’t say I never catch a break; the break was getting the chance albeit a last-minute chance to right a wrong. We were left with now trying to find the assessments that would work.

 

As mentioned, you can’t go to a library or store and browse through all the assessments available to license and use in trials. We must work with the companies that own them. They have specialists that help you zero in on topics of interest, I combed through endless assessments. Nothing was right. I called on Jonah’s therapists. Who better to point me in the right direction then the teachers on the front lines administering these tests to kids like Jonah. His therapists gave me a list of tests, which I then requested to view from the owners. My guy chuckled when he pulled them for me. He said he wasn’t even aware that they owned the assessments, they were so old. On that note… I finally had something we could work with. The ALL-127 protocol is now finished and back with the hospitals Internal Review Board (IRB). We anticipate approval to be coming in a few weeks. Our site initiation visit is set for October 14^th. Our goal for first patient in is end of October early November. We will make our first milestone and be able to bring the rest of the participants in for screening and baseline after the new year. After that the participants will come in for two more annual visits.  Meanwhile the ERT mouse toxicology studies for ALL-027 will wrap up and we will head back to the FDA. If all goes smoothly the ALL-127 patients will proceed into the interventional trial. Truth be told I’d like to extend the study for at least a third year, sadly we don’t have the budget for it.

 

The study is extraordinarily expensive. Our hope is that once we start accumulating the natural history data that we will garner more pharma interest and find a financial partner. I have a feeling that once the study is published on clinicaltrials.gov that we will have more patients wanting to participate. It would be amazing if we could include all the San D kids that wanted to come. The participants are coming from around the world, over half of them don’t speak English. We must translate all the consents and other patient facing documents to their native languages and bring in translators to help them throughout the study. ALL-127 doesn’t just include cognitive assessments, there are numerous physical and clinical tests as well.  Labs, sedation for x-rays and MRI. It’s no walk in the park for the children or their parents. Their commitment to the study and desire to help bring forth a treatment is nothing less than heroic. 

 

The ALL-127 protocol is going the extra mile by including a video collection of daily living activities (ADLs) shot at home by the children’s caregivers.  There will be a retrospective portion as well, all the patients’ medical records will be reviewed for the onset of disease symptoms. All the data gets imputed by the site coordinator into a controlled data base. It took our team (Labcorp) almost a year just to design the database, in their defense I did keep making changes to the protocol.

  

I’m extremely proud of the video portion of the study, we’re working with Aparito, a company that has licensed HIPPA and GDPR compliant software program to manage patient data. With the help of our patient community our team came up with several activities that we hope will capture the participants real-time real-world experiences. Caregivers will video children performing daily activities in a natural setting, within standardized parameters for video capture which will hopefully cause minimal disruption in their daily routines. The video activities compliment the assessments performed in the clinic. The idea is to visualize, describe and score the children’s behavior, movement, communication abilities, and yes smiles that are hard or even impossible to capture in the clinic. Remember our young kids are always on the move, they can’t sit still and tend to run away. Our advanced kids smile if we're lucky, they're cared for 247. I'm hoping that our video tasks will capture a few smiles and any incremental improvements seen by families after intervention.

 

These videos are taken on a smart phone using an app, the families are given a secure QR code where they download the app, which has been designed and translated to walk them through all the activities and questionnaires. The videos will be taken within 14 days of the clinical visits and at 6mo time points in between the clinic visits. We named the app RARE Recording Application for Real-world Evidence. The San C version is called C-RARE, get it? Sri came up with the acronyms.

 

When supporters donate to medical research, the primary thought is the cost and time of drug discovery in the lab. This is the tangible portion that can be visualized. It’s the behind the scenes and back-end work that you don’t see that takes just as much time and funding resources as the laboratory research. The contracts, study design and quality checks are sucking up all my time. Everything that goes into drug discovery must be meticulously collected, scored, and stored for FDA review.

 

In between reviews I have been working on new quality of life and clinical outcome questionnaires tailored to absorb as much as we can out of the Sanfilippo patient experience. These types of questionnaires are called Clinical Outcome Assessments (COAs) the cognitive assessments also fall under the COAs. Over the past ten years I have been told on numerous occasions that it is too hard to design and validate syndrome specific COAs. That I’d be wasting time to even try because the FDA wanted the ‘gold standard’ validated assessments that have been used in thousands of trials. It later occurred to me that the advice was coming from people that didn’t have a full understanding of the progression or phenotype of Sanfilippo syndrome or that the FDA had extremely little experience with Sanfilippo. It’s only been 10 years since the very first San A trial started. The FDA is just now wrapping their brains around the data coming from these trials. They have had a steep learning curve. 

 

A few months ago, the FDA came out with a new guidance that states if there is not an assessment available that is sensitive enough to measure your target endpoint, then make a new assessment, they go on to walk you through how to do it. I had already started to create a COA to measure behavior when this guidance came out. The FDA guidance was the push I needed to create a series of Sanfilippo specific COAs. The Sanfilippo families have been guiding us on the development of these COAs, patiently walking through every question and giving their feedback and suggestions for improvement. It has been an extremely rewarding experience for all of us.  My team engsged a couple of expert clinical assessment designers to help us with the scoring and wording of the questionnaires. When finished we’re going to pilot the COAs on the C-RARE app. We didn't finish the new COAs in time for the ALL-127 launch. They will however be done by the ALL-027 intervention trial.

 

The JLK-347 clinical protocol is being scrubbed by Labcorp’s quality control team right now!  Labcorp is the CRO managing our studies and storing the data.  We’re planning 2 sites, one in France and the second in the US. While the NHS for San C gets underway, we will finish up the tox and biodistribution animal studies (contingent on the grant coming in). The plan is for JLK-347 participants to transition straight into the interventional trial, JLK-247 and become their own controls. 

 

PN has been working on a third program that is suitable for all Sanfilippo subtypes, AVP6. It’s a peptide administered nasally which increases synaptic function. It’s an option that will pair nicely with gene therapy and ERT interventions.

 

I have taken the time to give you all an extra-long blog as I plan on being too busy to write again for another year! Tomorrow we will win the JLK-247 grant and begin our next chapter. Watch for the press release on Linkedin.Fingers crossed.

 

Quick Jonah update, he is doing great! He's still smiling and still learning. He just started his freshman year! Jeremy and I are so incredibly proud of him. This kid is fighting his fate like, Batman, his favorite superhero and he doesn't even know it.

 

 

I gave a few talks this year:

ADVANCE Sanfilippo syndrome workshop Cure Sanfilippo Foundation   

https://www.youtube.com/watch?v=UbtxDl20TyQ&t=3s                                      

My talk is on the ALL-127 program and RARE app. It starts at 1:30ish.  Phoenix Nest had three other talks. Srikanth Singamsetty discusses JLK-247, Tsui-Fen Chou speaks about ALL-127 and Alexey Pshezhetsky gave a talk on AVP6. The AVP6 talk and it's data were not published for wide distribution. You will have to wait until we publish.

NINDS Nonprofit Forum 2022

https://videocast.nih.gov/watch=45549

My talk starts at 2:17ish on day 1. Please watch the talk right after mine with Emily Caporello, NINDS and put a face with my "program director".

Decision Vision Podcast

https://businessradiox.com/podcast/north-fulton-studio/decision-vision-apply-for-grants-jonahs-just-begun-sanfilippo/

I spoke on my experience with applying for NINDS SBIR/STTR grants

 

RDLA- Rare Disease Week 2022- Policy Deep Dive: Speeding Therapy Access Today (STAT)act

https://www.youtube.com/watch?v=btB0cCzWoM8 

Spoke to how federal funding helps the ultra-rare disease community! My talk starts at 1ish

Check out the new FDA fit-for-purpose clinical outcome assessment guidance.

https://www.fda.gov/media/159500/download

Happy Birthday to me

 

Happy Birthday to me.

Phoenix Nest headquarters (HQ) are located at Industry City (IC) in what used to be known as Bush Terminal.  A massive manufacturing and distribution plant built in the 1890’s, 16 buildings on 35 acers right off the Gowanus Canal. In the 60’s there was a mass exiting of the manufacturers at Bush Terminal and the buildings fell into disrepair. Today they have been built back up but are still in keeping with their industrial roots. My loft space is rustic; beatdown in a good way, the best feature it’s windows. It is the ideal location for a houseplant garden. PN HQ is a silver lining on the horrors of my job. I feel like I can breathe here. Jonah loves it too, there is a great Pizza joint downstairs and a foosball table in the arcade room, but mostly he likes it for the tv.  My favorite addition to IC is the Little Pot of Soil, a plant shop down by the pizza joint. I think they put it in just for me. IC is my happy place; it must be as I pretty much live here. I received a B.day check in the mail from my mom yesterday and spent the whole thing on plants and pots for PN HQ. It was a good birthday.

 

I realize that I haven’t shared anything since Elouan passed away. I want to be able to get online and say we’re all done, Sanfilippo has been cured and we can all go home now. The reality is that research and drug development take a long time. There are hundreds of opportunities for setbacks. We try to control everything we can, but research is unknown, that’s why it’s called research.

 

For example, our IIID Enzyme Replacement Therapy (ERT), All-027 program enzyme didn’t like its food or temperature and wouldn’t grow. It took us a year to figure out the right food and temperature combination. That stretched our grant out an extra year. We ended up doubling the length of our IIIC mouse dosage study for JLK-247. Our mice were supposed to come down at 32 weeks, but we decided that the behavioral dated would be better supported with additional survival data. We extended our study to 70 weeks and just now took the rest of the mice down. Which again sucked up more funds. If only the money just flowed… Our third therapeutic study, AVP-6 hasn’t run into any major challenges.  We’ve gotten lucky thus far. Knock on wood.  

 

Last summer we won a NIH grant to support the observational study for ALL-127 (Natural History Study for IIID). The startup of this clinical trial has been exactly what I expected it to be, terrifying! I’ll go ahead and break it down for you. We have our main contract research organization CRO, Labcorp/Covance, these guys build the electronic Case Report Forms (eCRF) for us and store the data that comes out of the observational trial. They write the informed consent forms (ICF) and provide medical writers for our clinical protocol. They make sure we don’t miss anything and keep every letter in compliance with our regulator’s guidelines. The paper trail involved is astronomical. At the end of the study, they will do all the statistical analysis. All this costs just as much as the clinical trial itself. Secondly, we have the hospital site, they see the patients and perform all the assessments listed on the clinical protocol that we designed.  After each patient they input all the medical report results into the eCRF. We have two additional CROs that have helped us design a real-world real-time app. We call it the ‘RARE’ app. For the app we chose several daily activities for the caregivers to video record, this too, is a methodical research project. On top of that we will have a retrospective study where the patients will provide our study site with their medical records. The primary investigator (PI) will comb through the records and pull out our needs. The patients will come to NYC for a total of 3 visits over the course of three days for two years. The kids will go through a battery of clinical and cognitive assessments. First Patient In (FPI) was supposed to be in March we’re looking at September/October now. A few things happened, first we decided to move sites from Yale to Columbia. Secondly, was the change of cognitive assessments for the protocol.

 

Our All-127 grant is milestone based, one of the milestones was to present our clinical protocol to the FDA, for comments. The comments took me by surprise. I must hand it to the FDA; they did a great job providing insightful and helpful ideas and advice. It appears that they have learned a lot from the Sanfilippo trials that have gone before me. The San A and B trials have had a rough go at it. Most of them have shutdown entirely or divested, not necessarily because the drug wasn’t working, but because the sponsors didn’t have the bandwidth to give the drug enough time to show change.  I don’t think the sponsors fully appreciated how much time and resources that they would have to commit to their trials. For Sanfilippo it has become abundantly clear that we must put as much time and resources into designing the trials as we put into drug research and development. The FDA was kind enough to give me some ideas on how we might do things better than our predecessors.

 

Based off the FDA’s comments and my mother’s intuition, I pulled out all but one of the clinical outcome assessments that were considered the gold standard for Sanfilippo trials. Breaking the mold is terrifying, I’m ‘Scared all the time but doing it anyway’. This print is hanging in my hairdresser’s salon. It resonated with me. Wish us luck!

 

Thank you for all your support and generous Birthday donations. I want to be able to translate our patient facing documents to as many languages as possible. So that we can enroll more families into our RARE app video assessment. I'm a little shy of my goal. Just saying. https://www.facebook.com/donate/965299684110213/10158889015667215/

 Print by Margaret https://www.margaretstolte.com/

              

My new snapback, Bulbasaur hat, a Bday present from Jonah.

 

Longing for Loulou

My best birthday ever was Jeremy’s 37^th birthday. Jeremy, Jonah, and I traveled to Toulouse France to meet Guilhain, Francine andtheir 2 children, Laura, and Elouan. Our friend Elvis, from Queens, raised in Leone came with us. Elvis helped bridge the language gap and documented our meeting in this video.

This historical trip was 11 years ago this week.  Time flies so fast and I just want to stay in the past. The past being the south of France with our new best friends.

Guilhain met us at the airport grinning from ear to ear, huge hugs, and cheek kisses. Elvis whispered, look out country Frenchmen can be a little handsy. What I wasn’t prepared for was the country Frenchman’s driving style. Holy crap how he flew down the long windy road, sailing up and down the hills. Jeremy, Jonah and I were smashed in the backseat of his little European car. I tried to watch the scenery careen by out the window. It was foggy out and the sun was rising over a chilly winter morning. The road was flanked by acres and acres of fields, I caught glimpses of the shimmery frost on blades of tall grass.  It was literally breathtaking.

We pulled up to their house on the hillside and entered a lovely and lively home. Laura sat at the table watching her mom bustle around the kitchen prepping a breakfast for us. Elouan was dancing in front of the television watching Madagascar singing Let’s Move it Move it. 

Elouan a.k.a. Loulou had Jonah at Bonjour.

Our visit turned out to be our first patient population meeting for Sanfilippo type C and the formation of H.A.N.D.S. 

Belen, Pol’s mom from Barcelona came, she stayed at Guilhain’s sister and brother-in-laws house, who happened to be Spanish. Raquel, Joana’s mom from Lisbon joined as well, she bunked at Laura and Elouans’ grandparent’s house. It was quite the family affair. I loved that the entire family wanted to meet us and take part in helping find and fund a treatment for our children. 

Jeremy and I didn’t realize that we would be wined and dined for a week! Jeremy’s Birthday week no less.  Francine and Guilhain hosted us at the best French restaurants that the south of France had to offer. 

A relation shut down his restaurant to feed all of us, Jeremy had the best French deserts and was sung happy Birthday in 4 different languages (this happened all week long)! A reporter showed up to document the occasion; next day Jonah got to see himself in the paper.

Jonah was absolutely enamored with Elouan, he was 4 years older than Jonah and Jonah was at that age where big boys were like mega super beings to him. 

It is fascinating to watch little kids carry on a conversation in different languages. It really didn’t matter what they were saying, they had the same interests. 

Elouan had an awesome collection of cars that he happily shared with Jonah. The best was Elouan’s kids sized 4-wheeler, it was crazy watching Jonah, still a toddler, hop on that 4-wheeler ready to turn cookies.

 

Joana, Pol, Jonah, Laura and Elouan were all diagnosed within months of each other. We were less than a year into the diagnosis when we all met in person the first time. The diagnosis was still very fresh in our hearts and weighed heavily on our minds. But that week we put our fears aside and rejoiced in finding each other. 

We had already started to raise funds to put towards our gene therapy program at Manchester. Brian Bigger gave us a presentation that week over a skype meeting. I felt so empowered being with all our families, together we would conquer Sanfilippo. I still feel that way.

 

Elouan passed away early morning Friday January 14^th a seizure took him while in bed. I don’t know that I ever truly believed that our kids would see a treatment in their lifetime. I hope yet, temper my expectations, truthfully, I don’t let myself think about it.  I think we all just assumed that our kids would make it to their 30’s.  I’m lying I’m terrified that Jonah will die in his sleep and I’ll find him cold in the morning.

 

I just cannot believe that Elouan is gone. I cried all day yesterday. My phone started pinging at 4:30am, I turned it over to look around 6:00am. The shock, that feeling of disbelief, I guess this is how it happens. 

One minute everything is fine the next it’s not. Elouan had his first seizure last year and just a couple since then. We all know seizures can happen to our kids. We still all hope that it doesn’t and then when it does, it takes us by surprise.  

A few months ago, Guilhain messaged me late at night, which meant it was in the middle of the night for him. I asked him if he was having a hard time sleeping. He told me that since Elouan’s first seizure he was too nervous to fall asleep. He stared at Elouan’s room camera watching him sleep instead. Sometimes parents just know. 

France has a relatively large IIIC patient population. There are 4 families with 2 kids each, the 4^th family was recently diagnosed and has begun a full front attack on Sanfilippo. Their children are very young, a baby girl Eden and her older brother Abel. It was this family that Guilhain was texting me about that night. He told me that it might be too late for his children, but he was hell bent on helping Eden and Abel.

 

I love you Elouan, thank you for being Jonah’s friend. I’ll never forget the two of you singing and dancing: “LET’S MOVE IT MOVE IT!”

 

This disease is never going to stop unless we stop it. So, let’s move it.

You can donate for a cure in memory of Elouan at the Eden and Abel in French fundraiser  or in English.

A new paper provides answers to Jonah's behavior.

Extremely exciting and pivotal research for Sanfilippo syndrome coming out of the lab of Alexey Pshezhetsky. This paper explains so much about the early behavioral presentation of Sanfilippo syndrome. The paper deserves a blog to help frame the findings. BTW, not all bad behavior stems from bad parenting.

Early defects in mucopolysaccharidosis type IIIC disrupt excitatory synaptictransmission

Jonah was a runner, at one years old I could hardly keep up with him. Taking Jonah anywhere was terrifying. That kid would escape and be climbing up a guard rail before you even realized you weren't holding his hand anymore. Jonah was making all his milestones; we had no reason to suspect that something was wrong. He was hyper, but more than that he had no sense of danger.

Jonah was pushing 2, we had just received his diagnosis. The early days were hard on us. Jeremy and I thought we were going to watch him slowly die, but instead we were on constant suicide watch. Such insult to injury.

He once broke away from me at Prospect Park and sprinted towards Dog Beach, I jaunted along after him. Dog Beach was what the locals called the swimming hole for dogs, it was a smallish pond that was not railed off. You could walk right into it from land. I had his stroller with me, so I couldn’t run fast, I thought surely, he wouldn’t run into the water. When he made no sign of slowing down, I ditched the stroller and started sprinting after him. His foot reached the water’s edge and the other followed, I was not going to make it in time. I started screaming for someone to help. The clueless dog owners just stared at him in disbelief. Jonah was up to his waste and still running. A Hasidic Jewish man took one look at the runaway child and lunged after him. Seconds after Jonah went under the water, he lifted him up. Jonah was unfazed, I was crest fallen. The Hasidic man was drenched, his nice dress shoes ruined his cloak soaked his hat floating away. If he hadn’t been there.

All parents have one or two stories like this. Jeremy and I have too many to count. I tell this one to remind people to help when a mother is screaming for help. There must have been a dozen people that could have grabbed Jonah and they just stood there.  Actually, the airport incident at JFK had even more bystanders that stood by passing judgment. I started putting a vest on him with a leash attached to it. Talk about judging eyes.

This research has given us a new idea on how to approach treating the disease. A theory that I hope turns to reality. Stay tuned.

 

 

 

 

https://pubmed.ncbi.nlm.nih.gov/34156977/

Aduhelm brings Accelerated Approval to the spotlight

 

 

I have always been jealous of the vast amount of money and research that has gone into Alzheimer’s research. I figured if Sanfilippo had a tenth of the funding that Alzheimer’s research had, that we could have created a cure for all 4 Sanfilippo subtypes in a matter of years. But with all that money why didn’t Alzheimer’s have a ‘cure’ or at the very least a half dozen treatments on the market? It terrified me that a treatment had not been developed for Alzheimer’s. What did that say for Sanfilippo?

 

I realize now that Alzheimer’s shares the same problem that Sanfilippo does, it is a slowly progressing neurological disorder that lacks measurable endpoints. Meaning it is very difficult to prove that a drug has a visible effect on a patient. You can’t reverse brain damage (yet) but you can stop or slow the progression. But how do you know that the drug has halted the progression of the disease when the neurological decline is slow to progress?  Sanfilippo syndrome has one very important edge over Alzheimer’s. In Alzheimer’s there are several genes associated with the cause of the late onset version of the disease, making it harder to treat. For Sanfilippo we know the exact single gene defect that causes each Sanfilippo subtype, this allows us to zero in on that one specific disease-causing gene.

 

The FDA has taken a leap of faith and approved Aduhelm under its Accelerated Approval program. Instead of rejoicing this monumental approval, critics are gasping and calling for the resignation of FDA officials, including my personal hero, Janet Woodcock. 

 

I read this editorial by Dr. Kakkis yesterday, which led me to binge read 6 articles over the raging controversy of the approval . I took away three points that the critics had against the approval of Aduhelm. 

 

First point was that the critics didn’t think the drug was effective enough to grant approval.

 

That it was too expensive, and the applications were too broad, concerned that Medicare would go bankrupt. 

 

Critics suggested that a friendship between an FDA director and top Biogen exec, inappropriately swayed the FDA to not only approve Aduhelm but use the Accelerated Approval program to do so. 

 

For those that have been with us since diagnosis you must remember my obsession with the Prescription Drug User Fee Act PDUFA and The Food and Drug Administration Safety and Innovation Act FADASIA and the work that the EveryLife foundation was doing with their ULTRA and TREAT acts. Any of these acronyms ring a bell? This was back in early 2012.

 

I begged all of you in numerous email blasts from JJB to call your members of congress and implore them to include language from the ULTRA and TREAT acts advocating for 'Accelerated Approval'. I hope you remember because this blog is all about Accelerated Approval.  The language that we advocated our members of congress for was included in FADASIA and signed into law by President Obama on July 12^th 2012, this law was used to approve Aduhelm. You helped us get there. This is the language that we asked for:

 

 The Secretary shall consider how to incorporate novel approaches to the review of surrogate endpoints based on pathophysiologic and pharmacologic evidence in such guidance, especially in instances where the low prevalence of a disease renders the existence or collection of other types of data unlikely or impractical. -PDUFA V sec 506 pg. 94

I took the liberty of cutting and pasting the FDA’s definition of Accelerated Approval AA. To make the most of my blog please read the definition word for word.

Accelerated Approval

When studying a new drug, it can sometimes take many years to learn whether a drug actually provides a real effect on how a patient survives, feels, or functions. A positive therapeutic effect that is clinically meaningful in the context of a given disease is known as “clinical benefit”. Mindful of the fact that it may take an extended period of time to measure a drug’s intended clinical benefit, in 1992 FDA instituted the Accelerated Approval regulations. These regulations allowed drugs for serious conditions that filled an unmet medical need to be approved based on a surrogate endpoint. Using a surrogate endpoint enabled the FDA to approve these drugs faster.

In 2012, Congress passed the Food and Drug Administration Safety Innovations Act (FDASIA). Section 901 of FDASIA amends the Federal Food, Drug, and Cosmetic Act (FD&C Act) to allow the FDA to base accelerated approval for drugs for serious conditions that fill an unmet medical need on whether the drug has an effect on a surrogate or an intermediate clinical endpoint.

A surrogate endpoint used for accelerated approval is a marker - a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit. Likewise, an intermediate clinical endpoint is a measure of a therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug, such as an effect on irreversible morbidity and mortality (IMM).

The FDA bases its decision on whether to accept the proposed surrogate or intermediate clinical endpoint on the scientific support for that endpoint. Studies that demonstrate a drug’s effect on a surrogate or intermediate clinical endpoint must be “adequate and well controlled” as required by the FD&C Act.

Using surrogate or intermediate clinical endpoints can save valuable time in the drug approval process. For example, instead of having to wait to learn if a drug actually extends survival for cancer patients, the FDA may approve a drug based on evidence that the drug shrinks tumors, because tumor shrinkage is considered reasonably likely to predict a real clinical benefit. In this example, an approval based upon tumor shrinkage can occur far sooner than waiting to learn whether patients actually lived longer. The drug company will still need to conduct studies to confirm that tumor shrinkage actually predicts that patients will live longer. These studies are known as phase 4 confirmatory trials.

Where confirmatory trials verify clinical benefit, FDA will generally terminate the requirement. Approval of a drug may be withdrawn, or the labeled indication of the drug changed if trials fail to verify clinical benefit or do not demonstrate sufficient clinical benefit to justify the risks associated with the drug (e.g., show a significantly smaller magnitude or duration of benefit than was anticipated based on the observed effect on the surrogate).

 

In Alzheimer’s patients’ researchers have found that the protein, beta-amyloid builds up in the brains of patients. In this case beta-amyloid is the surrogate biomarker.

 

In comparison, researchers have found that the protein Heparan Sulfate builds up in the brains of Sanfilippo patients. For Sanfilippo Heparan Sulfate (HS) is the surrogate biomarker.

 

Unfortunately for our kids the FDA has not given HS the nod yet, but they just let beta-amyloid through so there is hope for us! Which gives me so much hope four our children. I would be over the moon excited if the FDA would grant the sponsors working on treatments for Sanfilippo syndrome Accelerated Approval for the lowering of Heparan Sulfate in cerebrospinal fluid.

 

BTW biomarker and endpoint are often interchanged don’t confuse yourself.

 

AA is here for disease like Sanfilippo syndrome and Alzheimer’s. Try and picture what it would take for a drug to show clinical benefit in a Sanfilippo child, you might be able to picture this in an Alzheimer’s patient instead. Other than brain damage and death, there isn’t a significant hallmark of Sanfilippo that is consistent throughout the Sanfilippo patient population.

 

Some of the common hallmarks of Sanfilippo are behavioral issues, sleep problems, diarrhea, hyperactivity, loss of speech, vision, mobility, and hearing. In the last stage children lose all their motor and brain functions and slowly succumb to death.

 

These main hallmarks are not consistent throughout the patient population, children might not suffer from all these symptoms, the degree of severity differs, and the timeline of presentation and decline is variable. Our patient population is considered heterogenous.  Now add to it the rarity of the disease.  Take Sanfilippo type C, I know of 20 patients in the United States, the youngest child is 6 and the oldest is in their mid-thirties, the rest of the kids are spread unevenly through this age range. No two kids are in the same place in the disease.

 

At this point we can’t use brain damage as an endpoint, our children that could never read are not going to start reading, the brain damage has been done. An attenuated child’s brain MRI might look worse off than a severely affected Sanfilippo child’s MRI. Death isn’t a good endpoint because we don’t have a definitive timeline of death, it could happen in the first decade of life or the third decade. Same goes for hearing, mobility, vision, and speech. We can’t have a trial that last 40 years.

 

Side note- there are nearly 7,000 rare disease, half of those affect children and one third of these children will not live long enough to see their 5^th Birthday. There are only 400 treatments for these 7,000 diseases. Think about that. It’s not because we can’t treat them. The science is here, but the incentive to produce a drug is not.

 

If the majority of Sanfilippo children died by 5 then we would have a good endpoint for our clinical trial. Most Sanfilippo children are not always diagnosed before the age of 5. Furthermore, the validated assessments currently used in clinical trials are not sensitive enough to see the change in our kids. The old gold standard tests that the FDA relies on are not designed for patients like ours. For instance, for mobility and endurance trials, sponsor use a test called the 6min walk test. It is exactly as it sounds; a patient walks up and down the hall trying to stay in a straight line for 6 minutes. You can’t explain to a Sanfilippo child to walk down to a cone and back for 6 minutes. They literally do not understand, they might be able to hear you and can still walk but they don’t understand the message. Perhaps you could model it, but it’s not sustainable for 6 whole minutes. The child will undoubtably become distracted and run in the other direction or take off their shoe and throw it at you. Go ahead and laugh at the vision, but it is not funny. We have a major problem.

 

Hearing and vision tests can’t be done unless the kids are sedated even if we could get an IRB to approve sedation for hearing and vision assessments, we don’t have anything to compare it to. Sleep disturbances is another major issue for our kids, but extremely hard to measure during a trial. I’m hoping you have gotten the point.  To summarize, Sanfilippo is a slowly progressing, ultra-rare, heterogenous disease. And that is the root cause of the pain in the pit of my stomach and the heartbroken voice in my head that whispers: You’re wasting your time, give up and enjoy Jonah while you still can.

 

To answer the question forming in your head about what we are going to do to address these hurdles in the clinic. Well, we’re getting creative and designing tools and measures that will be sensitive enough to capture change in areas that we think we can show change in. This is a massive undertaking, it is costing us huge sums of money, time, and resources. All things we don’t have on our side. You know what we do have on our side? Accelerate Approval! Will the FDA grant us AA? Unfortunately like my colleague says, that question is as clear as mud.

 

What does a clinically meaningful change mean? That is for the patient to decide and when a patient can’t communicate, it is for the family to decide, with the patient’s best interest at heart. Meaningful change is not something that a critic with no experience in a situation like ours has any business commenting on. For me a clinically meaningful change for Jonah would be stopping his diarrhea. I’m not making a joke.

 

For another Sanfilippo parent it might be that they could walk out of the room for 5 minutes without their child opening the front door and running into the street. This is something that I imagine is consistent to what an Alzheimer’s patient caregiver would consider as a meaningful change as well.

 

If I can take Jonah to the playground without fearing that he might shit his pants that is meaningful change. For transparency’s sake it’s not that Jonah is incontinent, he can get to the bathroom in time if he is so inclined. Jonah often gets consumed by what he’s doing that he doesn’t want to stop to use the bathroom. If he were to need to use the bathroom at church he’d get up and go, but if he’s at the playground having fun, he might not leave, and no one can hold diarrhea back very long.

 

Jonah has defiled public bathrooms from coast to coast. When Jonah lets loose it’s usually before his butt cheeks meet the toilet seat. His pants are down around his ankles before he reaches the stall, leaving a slick, stinking, disgusting trail behind him. Like Pavlov’s dog hears the can opener and starts salivating. Jonah senses the cool toilet bowl behind his legs and instantly releases the rest of the contents of his bowels. Spraying all shades of brown soup down the wall as his butt closes in on the toilet seat. The runoff penetrates every crevice of the toilet. Picture walking into a Starbucks bathroom after Jonah has done his thing and tell me that diarrhea isn’t a meaningful endpoint worth a few of your taxpayer bucks.  Frankly that shit effects you too. You just don't realize it until you step in it.

 

My company Phoenix Nest is making an enzyme replacement therapy (ERT) for Sanfilippo type D and gene therapy for Sanfilippo type C. The other comparable ERT’s on the market run between $350-700 thousand a year. ERT is a monthly or bimonthly infusions for a patient’s lifetime. Gene Therapy is onetime procedure, other comparable diseases have priced the procedure at a million dollars. Aduhelm, is priced at $54,000 a year, which is nothing in comparison to how much families pay out of pocket to care for their cognitively impaired parents or children. We must bring assistants into our homes, send our kids to private schools, our parents to assisted living homes, we buy medical equipment, all kinds of palliative care therapies and over the counter regiments. For many families one of the parents must quit their job to stay home with their child or parent. That’s at least $50,000 right there. Not to mention the strain it puts on families emotionally and financially.

 

EveryLife Foundation released a study analyzing the financial and emotional burden on families caring for rare disease patients: Economic Burden of Care Disease Study The report found that in 2019 $966 Billion dollars were spent out of pocket, representing 379 rare diseases made up of 15.5 million Americans.

 

The FDA did the right thing by using Accelerated Approval for Alduhyme. Alzheimer’s ticks off all the requirements for the AA pathway. Furthermore, I don’t see any crime in an FDA employee knowing a Biogen employee, people in our space run in the same circles. Knowing someone across the isle and seeing that person at a conference or speaking on the same panel can’t be helped. Lastly, the FDA is supposed to be our partners in developing treatments. Their job is to help us find a regulatory path forward, if at the end of the trial the data shows that no meaningful benefit has been met, then the drug isn’t approved. In the case of AA, if after Biogen's phase 4 confirmatory trial shows no meaningful benefit, then Alduhyme will be pulled. I get the feeling that the uproar in the news is to sell papers and give people something to complain about. It has become our National past time to throw our regulators and policy makers under the bus.

 

I admit I was a bit skeptical about Biden’s decision to replace Dr. Janet Woodcock with Dr. Patrizia Carazzoni, I didn’t know anything about her, and I really like Dr. Woodcock. I am delighted that Dr. Carazzoni has come out strong, straight out of the gate and right on top of the COVID crisis. Impressive! Now if Biden would hurry up and confirm Dr. Woodcock as the White House official FDA commissioner. 

 

Another great new piece of legislation coming out of the EveryLife Foundation the STAT act.  STAT is asking that the Federal Government to create a Center of Excellence for rare diseases.  Please sign on and spread the word.

My hero, Dr. Woodcock photo taken October 2013 at the EveryLife Foundations Abbey Award ceremony. Both Dr. Woodcock and I received an Abbey that year. I received mine for the advocacy work that I put into getting the Accelerated Approval language added to FADASIA.  I was extremely honored and proud to win an Abbey and to be standing by Dr. Woodcock's side.

An open letter to Maggie Baird (Billie Eilish's mom)

 

May 6^th ,2021

#BillieEilish

#MaggieBaird

#SaveConnor

Dear Maggie:

 

I bet you never imagined that you would raise a teenaged mega-star?! Not because it wouldn’t be possible, but because it didn’t matter. We love our children no matter what. I’m the mother to Jonah a special needs child. The term special needs can mean so many different things. For me it’s what I say to new acquaintances when we’re talking about our kids. An attempt to avoid awkward situations by giving the other parent a heads up.

 

I watched the documentary. You don’t often see extraordinary parents just being parents on tv. I stumbled onto your children’s music when googling the release for ‘No Time to Die’. I realize now that I might be the last person on Earth to hear of Billie Eilish.  Your children are profoundly talented, but you stood out as one tremendously gifted mother. It was hard watching the teenager angst, Billie brought back memories of my teenage years that I wasn’t interested in reliving. I turned the documentary off halfway through to give my brain a rest and finished it the next day.  I was especially motivated to see how you and Patrick were going to shoulder the responsibility of your stressful parental job. I just couldn’t imagine.  I’d like to think that if I was in your situation that I’d respond in the same way that you have. A standing ovation to you and Patrick!

 

Our son Jonah was so incredibly wanted; you don’t know how much until they’re actually here. I remember laying him in his bouncy thing in front of the television set. My husband and I took our meals on the couch, tv off, content on just watching Jonah sleep. He was so delicious, I ate, slept, and breathed him. 

 

On Jonah’s first year well visit we took him to see a new pediatrician. Dr. Cao noted that Jonah’s head circumference was not typical, he wanted us to get an MRI to rule out hydrocephaly. I thought it was stupid, Jonah was perfect in every way, he had a big head that’s all. I liked the doctor and knew if we were going to continue to see him that I’d have to follow doctor’s orders. We had three cancelled MRI appointments, over the course of 6months, all for different reasons. I was so annoyed I almost just dropped it. Jeremy convinced me to take Jonah to NYU Langone. During that time, we enjoyed the perfect Norman Rockwell Christmas with Jonah.  

 

Away from NYC snuggled in at my Mom’s cozy home in Oregon. Jonah was 17 months and walking, running actually.  He was non-stop, but that morning, Christmas morning, Jonah was dazed.  He woke at 5:00am and headed downstairs on his own, I jumped up and followed him. When he got to the stairs and looked down, he paused, dumbfounded. He walked slowly down the stairs holding onto the handrail, fixated on the tree as if it was a mirage.

 

My mom always displays a few presents unwrapped and out of their boxes. Jonah made his way towards those. My husband and Mom came down, we turned on the fireplace and made coffee and watched Jonah. The sun was rising, it backlit Jonah, his hair was the color of a peach, he glowed a Christmas morning brilliance. He was wearing a red and white stripped elf pajama onesie. His chubby little toddler hands putting together wooden puzzles. My heart grew twice the size that morning and unlike the Grinch’s it was already big. For this memory I am forever thankful for all the cancelled MRI appointments.

 

It was Spring by the time we finally got Jonah successfully through an MRI appointment. When the neurologist called me in for the results, I had completely forgotten about the MRI. Jeremy randomly had the day off of work, he offered to come with me, I told him to stay home and enjoy the day off, but he insisted. Another, thank god moment…. When we got to her office, there was an intern in the room with our doctor. The intern couldn’t make eye contact with me. You know how you know without knowing that something truly awful is about to happen. That twinge in your side.

 

Our neurologist looked Jonah over from head to toe asking dozens of questions. I was a bit relieved to be answering the questions in Jonah’s favor. She didn’t seem to find anything out of place, maybe I was just a nervous mom. Then she sat down at her desk and looked at me. Jeremy was getting Jonah dressed in the back of the office. She didn’t wait for Jeremy to join us, she started in on her deliverance. The results pointed towards a rare disease called mucopolysaccharidosis (MPS). Stop right there. WTF did you just say? 

 

She just kept plowing through; she explained that there were several versions of MPS, but that she suspected MPS III, also known as Sanfilippo syndrome.  I started to well-up, I turned to look at my husband, who was still oblivious to what the doctor was saying.  Jeremy saw the tears streaming down my face and sat down. The doctor passed us a handful of prescriptions and tissue, it was evident that she had done this before. She explained each RX and why we needed to go. A sleep study, head to toe x-rays, another MRI of the spine, ENT, allergist, EEG, liver and spleen sonogram, GI and cardiologist appointments, but first we needed to go to the geneticist.  She had already made the appointment for us. Lastly, she implored that we not google mucopolysaccharidosis when we got home. Of course, we did not heed her warning.

 

Walking home, Jonah in his stroller, my husband and I were numb, we couldn’t get our words out. I felt like I was walking on the sea floor with cinderblock shoes. We stopped at the wine shop and grabbed a bottle. Made dinner for Jonah and began the bedtime routine. As soon as he was down, we opened the bottle and googled Mucopolysaccharidosis. The results were unbelievable; there just had to be some kind of mistake. We forced ourselves to believe that it was somehow some freak mix-up at the lab.  For the next few weeks, we kept telling each other that it was wrong, it was going to be ok.  Jeremy went back to work, and I took Jonah to the appointments alone. We waited for blood results to come back. When they did, we were called back to the geneticist’s office, we arrived at the elevator at the same time as our geneticist. She looked at us, excused herself and took the stairs.

 

I don’t want to write this anymore. I hate telling my story, I won’t be able to sleep tonight. I wouldn’t mind if you put this letter down and took a mental break. This is a mother’s worst nightmare.

 

Dr. David confirmed the neurologist’s assumptions, Jonah had MPS III aka Sanfilippo syndrome, we still had to find out which subtype Jonah had. From our google search Jeremy and I already knew that Sanfilippo was the only MPS that did not have a treatment and was terminal without one. Death could be as early has 5 or possibly 25, depending on the subtype. So, there it was, we couldn’t deny it anymore. I can’t even begin to tell you how bad this sort of news hurts. I looked at the geneticist through my tears and asked her if this was a death sentence. She took so long to respond I hated myself for asking, but I had to know. She came back and said: “Today there are treatments never thought possibly, just five years ago.”

 

That was all I needed to hear. I hit the ground running!

 

There are 4 subtypes of Sanfilippo: A-D.  A and B being more prevalent and more severe, types C and D are uber-rare, but thought to be less severe, but nobody really knows because it’s so rare. Types A and B both had research that looked to be heading towards clinical trial, so that was a bit comforting.

 

Jeremy and I went home, this time we started making phone calls, first to his brother, a lawyer, we asked him to draw-up the paperwork for a 501-C3. I called my mom and all of our good friends’ and rallied the troops. It was May 15th, 2010, we held our first fundraiser a few months later in Oregon, a wine tasting event. While I begged for money, Jeremy went to London to join an MPS conference. His mission- to seek out the scientist that would create a treatment for Jonah.

 

Jonah’s results came back type C. There were a couple of papers written on type C by a scientist named Alexey Pshezhetsky, from Montreal. I called his lab, he didn’t answer, I left a message. Alexey had discovered the gene that caused Sanfilippo syndrome type C. It was a month before he called me back. He had been on a rock-climbing trip in the Himalayas… who does that?! Anyhow, he apologized profusely in his watered-down Russian accent. “Yay, yay of cause of cause, I’m interested in MPS IIIC, it’s just that nobody asked me to do anything about it, so I haven’t.”

 

Alexey said the first thing I needed was a mouse model. He’d be happy to make us one, he had an idea about using chaperones as a treatment. We raised $40,000 at our wine tasting event.  We met another family that kicked in another $40,000, we gave it all to Alexey’s lab. A year later we hosted our first patient population and scientific workshop in NYC. Which was held at Columbus Children’s hospital and benched by our new Scientific Advisory Board for our new not-for profit, Jonah’s Just Begun (now dissolved).

 

We brought in three scientists from three different countries and the handful of parents that we had assembled. Over two days we listened to our scientists hash out the best path forward for a treatment. We all went home motivated, the parents started fundraising and the scientists’ started interviewing for postdocs.

 

That was 11 years ago almost to the date. We’re coming up on several observable days, my husband and mines anniversary is tomorrow the 6^th, today being Cinco De Mayo, Mother’s Day is in a few days and National MPS awareness day is the 15^th. Nothing planned for our 15^th anniversary, I did see some peonies at the flower stand on my way to the office. I’ll get a bunch and tell my husband that they’re from him, he’ll be relieved.

 

Observable dates, Jonah’s diagnosis date, can’t believe it’s been 11 years already. We had assumed that Jonah would not be walking or talking anymore by now. We assumed wrong! Jonah is fighting his fate, turns out that he has an attenuated form of Sanfilippo. Meanwhile we’re watching children Jonah’s age die from this insidious disease! For the doom and gloom of Sanfilippo, I’ll let you investigate it yourself. https://curesanfilippofoundation.org/

 

Maggie, this is my ask, mom to mom, would you please share a link for me? This is the story of Connor and his family, together we’re fighting to save our kids, saveconnor.com 

 

I think you’re the perfect role model to endorse our cause. Please consider sharing on your Instagram site.

 

I know I don’t have to tell anyone anywhere in the world how awful COVID has been for everyone everywhere. I hope that you can help us keep the momentum of this video campaign hosted on gofundme going. The parents are still working, and our children are also still dying. We have had to get creative with fundraising and work around the COVID limitations.

 

Over the past 11 years I have been slaving over this cause. I created a biotech, Phoenix Nest.  Our gene therapy program is ramping up, we’re almost ready to go to trial.  The only thing that stands between our children and a treatment is funding. I am so sick and tired of begging for funding. Potential pharma partners are averse to funding research for small patient populations, they worry about a financial return. My biotech survives off of federally funded NIH grants, the grants that Phoenix Nest won are all in support of a treatment of Sanfilippo type D, not C as in Jonah’s version. The grants are intended to fuel small business in the US.  My MPS IIIC research was primarily happening in Canada and the UK. I have recently remedied that by bringing our research to the US. I have applied for a IIIC gene therapy grant but I absolutely cannot count on winning it.  The competition is fierce. Even more so now that funding for the NIH and the FDA is tied up in COVID research. Furthermore, the grant review process takes over a year from submission to funding. I can’t stand waiting by and watching these kids lose all their abilities. Enough is enough.

 

Happy Mother’s Day! I do greatly appreciate your contribution to the world.  Your children’s music has been a much-needed distraction. Billie also inspired me to bleach my hair blonde and die my roots pink. I will be on the look-out for when Billie comes back to NYC.

 

Best of luck to all of you!

Jill Wood (Jonah's mom)

 

 

 

 

Jill and Jeremy @ Central Park, wedding day May 6th, 2006