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

Is silence compliance?

  

Is silence compliance?

 

I have grown a lot over the 10 years since Jonah’s diagnosis, but I still feel like a kid.  I’m hungry to learn and experience new things. Like a little baby, wide eyed soaking it all in, touching everything, sucking on life hoping to learn something from the taste and texture. It’s not possible to discover what you want to learn in a single lifetime. I’ve always been impressed by kids that knew what they wanted to be when they grew up and followed through with their aspirations. I was never drawn to any one particular vocation. Why did I have to choose just one career? There is so much to do, so many possibilities. As life would have it, I didn’t have to choose, my job chose me. It quite literally chose me, Jonah landed right in my lap.  Now I have more jobs than I know what to do with.

 

Math, science and public speaking were never my strong suit. I was terrified of public speaking, I don’t like people looking at me, judging me. A propensity for math and science, chemistry in particular never came to me. I admire the people I work with, they worked hard to earn their doctorate and medical degrees. I have never felt worthy of being in their league, I feel guilty, it’s imposter syndrome.  For the most part this feeling of inferiority is on me, my colleagues have never treated me as inferior to them. Quite the opposite, they have embraced me and lifted me up. Who I am has rarely been held against me by others in this space. I feel good about who I have become and I look forward to all the new things that I will continue to learn. I have finally settled into my job; it’s not so intimidating anymore, and I actually find it exciting.

 

Writing NIH grants is a talent, not only do you have to have a worthy proposal, you also have to compile a grant in such a way to meet the specific and strict standards of the NIH. These processing rules are not self-explanatory. There are a lot of fine print requirements, the formatting of the grant is somewhat of a test in itself. The application process is harder than the science; easy for me to say, I’m not actually working in the lab. Last grant round we submitted three grants, they go to review in November, yesterday we got word that one of the grants was rejected without review.

 

My contribution to the team is my firsthand connection to the patients and intimate understanding of the disease. I realize now that what I bring to the table is invaluable. My life experience is also the basis of my imposter syndrome, I don’t have a medical or science degree and it weighs on me. My biosketch was written by my former CEO, I thought Sean did a nice job of presenting my strengths and value to the team.  Our grant was removed from review because my biosketch contained a hyperlink to this very blog.

 

The grant rules include a clause that hyperlinks are not allowed in the grant due to security reasons. The clause says this https://nexus.od.nih.gov/all/2019/05/13/the-dos-donts-of-hyperlinks-in-grant-%20applications/

At the end of the day, risk avoidance may be the most convincing reason to avoid unrequested hyperlinks. NIH may withdraw your application from consideration if you include them. Don’t risk it. Write a compelling, self-contained grant application and let it speak for itself.

 

This is good advice and I wish I would have taken it. However, I don’t think it’s fair to say that a biosketch is part of the scientific portion of the grant application. To me a biosketch is a supporting document not the grant. The grant was exceptional, if I do say so myself, we will resubmit without the hyperlinks in January.

 

The response from the NIH to our rebuttal for disqualifying our grant for a hyperlink gave me pause, the wording of the rejection letter was ambiguous. It could just be that pesky imposter syndrome sneaking up on me. Out of fear of retribution I will refrain from writing what it said. Was it the hyperlink and fear of malware that concerned the NIH or is it that I write a personal blog which was seen as a breach of security? Had a reviewer read my blog in the past and was uncomfortable with something that I said? From one vague line of reasoning in the rejection letter I got the sense that someone held bias against personal blogs. If the shoe was on the other foot, I might see me as a liability too. It’s really hard to not judge someone by what they write.  I know that employees of the NIH have read my blog. I was invited to speak at an NIH workshop in part to what the organizers read in my blog. The whole thing has put a bad taste in my brain, and I hope after writing about it I can put it behind me.

 

My first reaction was to delete my blog, I have always feared that my blog would come back to haunt me. At the end of the day I keep the blog to face my fears, testing my convictions gives me strength. Swallowing my pride and putting myself out there has proved to be my most valuable skill set.

 

My biggest fear is that I will not be able to fund our clinical trial and I will have failed all the families that have hope because I told them they could. I believe in our science I believe that with the approval of our gene therapy program and newborn screening that we will save the next generation of children. I can’t promise that we will be able to save this generation of children, because I can’t promise that we will have the funding to complete our research. Funding is the only thing that stands in our way. Once my company creates a treatment for Sanfilippo, I hope to be able to reinvest drug proceeds into research for other rare diseases. No parent should ever have to hear: “your child has a terminal rare disease and there is no treatment.”

 

I have so much conviction of seeing this through that I have turned my life and my family’s life into a constant state of financial and emotional flux. Thursday- after listening to the presidential debate, I actually asked myself, would I give up winning these grants to see Trump out of the White House? What is more important to me, Trump out of the picture? Or immediate funding to treat our Sanfilippo children?

 

I’m aware that I’m making an egregious social media faux pas for speaking my mind about Trump. My son’s life is on the line and I need funding from any political party to help save our Sanfilippo children. Here is where my moral convictions come into play. I do believe that silence is compliance and I can’t silently stand by and watch Trump mock everything that I hold so dearly. My son has ‘bad genes’ that he got from me and my husband, which caused him profound brain damage. Jonah will need assisted care for the rest of his life.  Where do children like Jonah fit into a Trump dynasty?  I know Trump sees my child as weak and a failure, not worth tax-payer dollars. I know it because I have seen him in action, I don’t have to read is raving tweets to know that he’s a maniacal and unconscionable person that cannot be trusted.

 

If we’re able to get Jonah a treatment in time, I’ll be able to halt the progression of the disease and he’ll most likely outlive Jeremy and I. Jonah doesn’t have any siblings to look after him when we’re gone. I’ll have to trust our government to meet his needs.

 

Please think of Jonah and all the other vulnerable children when you cast your vote. Do you believe that Donald Trump has the best interest of the vulnerable and less fortunate at heart? Actions speak louder than words, I think this is true. People don’t always mean what they say, and their words are sometimes misunderstood or taken out of context. However, a person’s actions tell the truth.

 

One more favor, I’d greatly appreciate it if you would post this video on your social media platforms, in hopes that it will go viral and raise awareness for Sanfilippo syndrome and funds for a treatment. https://www.gofundme.com/f/saveconnor  If you’re not comfortable with clicking a hyperlink you can google SaveConnor.com 

Happy Halloween! 

JW

#SaveConnor = #SaveJonah

 

Luck is in the eye of the beholder.

 

The goal that was named cannot be countermanded

 

The goal that was named cannot be countermanded.

I named my goal JLK-247 and it can’t be taken from me.

 

I see clearly now, and it feels good, I feel good.  All the parts have come together to form a map and I can’t wait to get where I’m going. Once I get there I won’t stay long, I’ll be off to live my life, free from that which binds me.  

The translation: Sanfilippo binds me and I’m going to the clinic with JLK-247 to get rid of it. Then Jeremy, Jonah and I will travel on living happily ever after.

 

I love looking at the map, I made a vision board for 2021-2022. I have a lot of mile markers on the board and I’m anxious to tick them off. The rendering of our vector is there too, it contains all the components that make up JLK-247, plasmids, capsid, AAV9, HGSNAT, a promoter and some other stuff. It’s beautiful, when we’re done, I’ll have it tattooed on my back.

 

This year has been one disaster after another.  These disasters are of our own making and they’re not going to go away by ignoring them, they’re just going to get worse and worse. Could 2020 get any worse? You bet it can! The solution starts with us, it’s time for people to get over themselves and start thinking about someone else. I’m hoping you won’t think about how much you hate the other person, but how you might come to know each other.

 

I have one huge agenda that consumes me, but I can’t ignore the bigger picture. Why cure Sanfilippo and save our kids to have them live in an infested world of hate, plague and decay? This is a rhetorical question. I love earth and people; I have faith that we’ll figure it out. It will take a lot of work, but it will be worth it.

 

JLK-247 is what I named the drug that we’re making. JLK stands for Jillian, Lindsey and Kelsey, three sisters who should be graduating from college, starting careers and families of their own. I think about this family all the time and how their parents care for them 247. It’s not my place to share the private lives of this family, I can share mine instead and you can times that by three.

 

No school and remote learning brought our family to the edge of the cliff. Jonah just couldn’t settle in, computers to Jonah are not meant for learning, they’re meant for entertainment. He’d have his good sessions and bad sessions, where he’d listen and follow instruction or not. The nightmare was with the technology, if the computer didn’t load fast enough or it crashed, any technical issue sent Jonah off on a rage. He took his frustration with the technology out on Jeremy and me. It was all our fault that it wasn’t working. He beat on us, he threw things at us, he screamed on the top of his lungs. All we could do was hide and try to get out of his way until he came down.

 

If I lived next to us, I’d either move or call the cops. I ran into my next-door neighbor the other day, when I say next door, we share a wall. She asked me how we were doing with such kind eyes, full of sympathy, I wanted to hug her for her understanding. I said, you know how we’re doing you’ve had to listen to us all summer.  She didn’t try to pretend like she hadn’t heard us, instead she said she was sorry that she feels helpless and wants to help somehow. Now this is a person that cares about her neighbors. We are so lucky to have her as a neighbor. Meanwhile the apartment below us has had three families move in and out over the 4 years that we have lived there. This last family just moved out, I checked the door handle this morning and it’s open. I’m going to go in and have Jonah run around upstairs to see how bad it is. Is it just a coincidence that 3 families moved out from under us?

 

For whatever reason, Jonah just stopped hitting us. The rage is gone, he still gets angry, but he doesn’t go after us. It’s like a switch was flipped and he can now control himself. It makes no sense, but I’ll take it! In retrospect, his ear was filled with oozing gunk for the majority of the summer which could have contributed to his behavior.

 

Jonah has not gotten out much since COVID a normal summer would have him in camp during the weekday and at the playground on the weekend. Every weekend he walks to the office with me, where he gets to watch T.V. all day. He’s here with me now.  On one of these walks, I noticed that his gait had changed. Jonah is walking on the inside of his feet and his knees are turned in.  I need to get him into the orthopedist and see about some braces. How fast will he lose his mobility? Most Sanfilippo kids his age, have wheelchairs for outings.  This weekend thing started by giving Jeremy a break, Jeremy has been doing all the home schooling, which is going to start up again tomorrow. For now, it’s one week at school and the next week remote learning. I’m actually not that concerned about sending Jonah back to school. He only has a handful of kids in his class and on his buss. His teachers are not run of the mill teachers, they’re highly trained specialists. They have had experience with numerous medically fragile children, I have confidence in them. I also have confidence in the parents of the other children. I don’t believe that any of the parents from this school would put another child’s health at risk. We’re all ‘special’ kids here and we appreciate that. Furthermore, what’s happening to Jonah’s intellect and body supersedes the fear of COVID.

 

My goal is to be in the clinic by October 2022. My heart lifts every time I say that. I have never been able to say a date with such conviction. I know it can be done if and only if the funds come in. We’re working with a not for profit called the Columbus Children’s Foundation, the foundation was co-founded by Jude Samulski’s company, Asklepios, Viralgen and Columbus Venture Partners. The mission of the foundation is to help people like me accelerate gene therapy. Asklepios reassembled our vector for us last year, when we decided to grade up from a single strand vector to a self-complimentary vector. Asklepios works hand in hand with Viralgen, Viralgen is the vector core plant that is manufacturing our vector for us. The Columbus Foundation acts as our broker, they negotiate the cost of our vector with Viralgen and Phoenix Nest pays the Foundation. The exact price of our vector production is confidential, but I can tell you this, we are saving 3.5 million dollars and just as importantly we will be expedited to the front of the line! No waiting in a line shaves off a year! A year can mean losing the skill of walking.

 

Every piece of this puzzle that we have been able to foresee has been sorted out. All of our ‘vendors’ have been contracted our statement of work agreements have been sorted, the investigators and sites have been chosen. The interventional trial design is a work in progress, we have designed the Natural History Study protocol, which will be the lead in study to the interventional trial. That data derived from the NHS will decide the course of the interventional trial. The NHS is a 2yr study the kids will go in 3 times, first will be the base line, the second will be a year later, the same procedures from baseline will be conducted again. The last visit will be right before the interventional trial. We will have three data points in which to compare the ‘on drug’ data to. The NHS is the control arm. On my vision board, I have the goal of the first child enrolling into the NHS this October. You see the interventional trial with JLK-247 can’t start until the NHS i.e. the control arm is completed!  The pressure is on. I just can’t stand waiting anymore, it’s figuratively killing me and is literally killing the kids.

 

How will we pay for this? Grants, V.C., not-for-profit fundraising and a whole lot of pro-bono work. These resources are all on my vision board too. I finished my pitch deck and sent it off to a VC last week, we have three grants in now and will be submitting a fourth late October.  We should know by November if we scored high enough for funding, April is the earliest that we would receive any funding. For transparency sake one of the grants is for our IIID program, 2 are for small molecule programs that could translate to all four subtypes and the 4^th one going in in October is for our gene therapy program. We can’t write 4 grants on the same subject and send them all to the NIH for funding. They have to be different approaches and they’re all going to different grant calls but the same funding source.

 

I have been training for an ultra-walk fundraiser apply named ‘Step-Up’ that is happening in Philly on October 11^th. It’s a Rocky theme. I watched Rocky for the very first time, last month. I actually didn’t realize that I had never watched it. It’s a timeless movie that penetrated our culture so well that I thought I had seen it firsthand. I can’t believe how much I loved it! My next blog is going to be all about Rocky and the symbolism of this walk.  I’d love it if you watched the Rocky movie and joined my team. If you can’t do either of those things, you can donate or share to someone else that might want to be part of this thing. It’s all about changing what you can to make the world a better place for everyone. 

 BTW the line: The goal that was named cannot be countermanded. Came from Walt Whitman’s poem the ‘Song of the Open Road’.

 

 Jonah's back to school haircut, he's starting 7th grade tomorrow!

Step up