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| Buy me something so I can re-gift it. http://bit.ly/JJBWishlist |
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| Red Tail Hawk at Greenwood Cemetery, just chilling. |
Jonah is doing really well, he’s super funny and charming, even when he doesn’t mean to be, which is most of the time. I’m not living in denial, my entire week is consumed with the logistics of how we’ll bring a treatment to trial and then to market. I know exactly what will happen if we don’t. It’s just not worth obsessing over when he’s going to die or when will the treatment come. Live Life!
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| Happy Mother's Day, Anniversary and MPS awareness day to me. |
Recently we have had some pretty big negotiations and projects come to fruition. Anticlimactic to say the least. It took over two years to sort out the terms and conditions on our exclusive licensing rights for our ERT type D program with LaBiomed. There was a lot of arguing involved, more back and forth then you could ever imagine. The fact that I have to go through these legal negotiations in the first place is a put off. Phoenix Nest, our virtual biotech funded all the research to date. JJB won the creation of the knock out MPSIII D mouse model years ago, which put the science in motion. There are 2 people, twins, in the United States. Yes, I'm sure more children (young adults) will come out of the woodwork when we go to trial. Can you imagine trying to convince pharma to help you commercialize a treatment for two patients, in the US, possibly a 100 world wide? Yet, I had to fight for the terms we got. The IP departments at University’s can be greedy and tenacious. Phoenix Nest has won over a million in grants to support this research. Phoenix Nest funds post docs that I have not met in person, they're great to work with though and I purchase equipment that I can’t even pronounce. Add grant manager to the list of my qualifications and I do the work for free.
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| That 'thing' cost $80,000. |
I would not have been able to get this far if it wasn’t for Sean, my grant writer and CEO of PN, Peg our pro-bono lawyer from King&Spalding, Mary & Amy at McConville, Considine et al and my bookkeeper Deb. Mari, well she goes without saying.
Meanwhile I’m working on the same type of deal with an intellectual property department in the UK for the exclusive licensing rights for our MPS III C gene therapy program. Negotiations have gone a little more smoothly, but only after I contacted the Dean of the University and flew out to talk face to face with the manager of the IP department. The terms have finally been agreed upon, they can’t go back now. I’m just waiting on one little signature from an outside collaborator, then PN will have the exclusive licensing rights to our gene therapy program. These guys were smart enough to add a clause in our contract stating that I couldn’t disparage their name in public. LOL Not that I would, I think they just got nervous after I called the Dean. Sometimes a little threat is what you need to get the ball rolling. The signing of our Gene Therapy agreement won’t be as anticlimactic. Our MPSIII C GT is nearly ready for trial. There is one MAJOR hurdle that we have to address, licensing and manufacturing the vector. I have to depend on my collaborators to move this portion along, this one is a bit out of my hands. I will lean hard on these people to move it along.
Years ago PN received the exclusive licensing rights for a chaperone molecule for MPSIII C and D. Working with the entity that holds the original patent was seamless. Every institution is different. We have been modifying the compound for a couple of years now. Every 4mo we get several new versions of the original compound and it keeps getting better and better. The original version rescued enzyme but it was too toxic. We work with a chemistry group to help us design the new compounds, which are then sent to Alexey to test. The research lulled last winter when JJB couldn’t afford to replace the postdoc who left. Jeremy and I sold our parking spot and granted the money to Alexey, our new postdoc is now testing the backlog of compounds with great success. Our chemist is already working on additional designs from the new leads. This is the kind of stuff I get excited about.
Our chaperone program gets the least funding attention from our consortium HANDS, because we have placed Gene Therapy as our top priority. A chaperone for Jonah or anyone with a responding mutation could be our silver bullet, but it won’t work for all our kids. Gene Therapy is for all of our kids, the late staged young adults might opt to not have the drug. We continue with the chaperones, for several reasons. For late staged patients this is a more favorable approach then GT. Also the chaperone that we’re creating will most likely have implications for other lysosomal storage diseases. Gene Therapy (GT) is a one time surgery, a chaperone treatment is forever and can enhance GT. Brining us as close to a cure as possible.
Alexey also has two other MPSIII C programs in his lab. But that’s enough for the science for now.
Our Natural History Study has FINALLY been approved by the Internal Review Board (IRB) at Montefiore Children’s Hospital. I swear I thought I was going to have to beat someone up, I called the boss too, but I think you have to be scared of your boss to pickup the pace.The IRB is now with the National Institute of Health and waiting for approval. Dr. Levy, Paul is a very calm thoughtful man. He reminds me of Jeremy, he can’t be rushed and sometimes I just want to wring his neck. He is passionate about the kids and prioritizes them over the science. A lot of PI’s conducting trials of this magnitude put pharma first, Paul can’t be bought. His ability to connect with children is priceless, he can put children at ease, which makes for a productive visit. I’m anxious to meet our Neuropsychiatrist, I realize now the crucial role that she will play.
When Jonah was first diagnosed we drove out to North Carolina to meet with a geneticist, neuropsych etc.. We were at the clinic for a few days, the first day Jonah threw up all day. We waited out a day at the hotel hoping he’d get over the bug before we did the cognitive testing. The next day Jonah was still irritable, not vomiting anymore but not happy. We met with the neuropsychologist and she immediately got down to business, ushering us all into a little room. The back of the room had a few book shelves, the other walls were lightly decorated and kid friendly the room was taken up by short round table, surrounded by furniture. The furniture overpowered the room, there were no windows and it was claustrophobic. Jonah was anxious he wanted to be free to move around. The doctor was commanding, she didn’t try to engage Jonah and win over his affection. I was surprised by her rigid borderline militant demeanor. She knew that Jonah had a profound neurological disorder that caused caused cognitive delays, brain damage and sever behavioral issues. Her job was to administer a few cognitive tests, to do so she needed Jonah to be comfortable. She didn't bother to get to know Jonah and disarm him. I didn’t get it, I thought maybe for our sake she wanted to get us in and out. Later I learned that the evaluator was an outside contractor and her original appointment with us was cancelled because Jonah was sick, so she had to reschedule, I’m thinking she was pissed about having to rearrange her schedule. I’ll never know the truth.
On top of her abrasive personality, she had two different colored eyes. Not something you see everyday and not something Jonah had ever seen. Her job is to administer cognitive tests to children with neurological and behavioral disorders, kids like Jonah have irrational fears. Animals and anyone in costume freak him out (he’s almost over this now). Probably not the wisest career choice for her. Jonah lost it, he was inconsolable, he wanted to leave charging at the door, screaming bloody murder. The evaluator was incensed, she kicked me out of the room, insinuating that I was the reason for Jonah’s ‘bad’ behavior. I was ready to leave, the whole experience was cruel, Jonah was sick, scared and tired. Jeremy was willing to try and hold down the fort, out of spite I agreed to leave. Knowing full well that things would only get worse if I left. I sat down the hall in the waiting room. Jonah didn’t stop screaming for one second, he was inconsolable, I don’t know how long I let him scream for, it felt like 20 minutes. Enough was enough I stood up and walked down the hall, just as I was about to knock the doctor opened the door. She was harried, sweating her eyes bulging.
She attempted to apologize, then switched gears stating that a child such as Jonah needed strong discipline, if we didn’t do it now we’d never regain control of him. I took Jonah in my arms and we left. Never to go back again. She was right that Jonah and our family would need extra help to negotiate his behavioral issues. But that day was not the time nor the place, Jonah was upset with just cause. Instead of setting Jonah up for success, she brought out the worst in him. Jonah didn’t know any better, but she should have. He was 2, sick and scared.
The silver lining…. I learned an invaluable lesson. Five years ago I didn’t know that I’d be lining up the team of doctors for our Natural History Study. I know first hand what it’s like for a parent and what works and doesn’t work for our Sanfilippo children. I will make sure that our families do not meet with the same arrogant belligerence. The NHS, is a five year longitudinal study that follows the course of the disease. The kids will come in once or possibly twice a year, they will have one day of clinical testing and another day of cognitive testing. If the children are upset during the cognitive tests it will affect the results of what they’re really capable of doing.
For parents starting down this road, take note and choose your team very very wisely. Ask yourself if this is the doctor, scientists or institution that you want to work with side by side for the next ten years….
What’s next…. We’re waiting for lambing season to begin again, which won’t happen again until next season…. Who knew.
We injected 12 healthy sheep last Winter. We’re looking for the best distribution avenue into the brain for our gene therapy. Explanation… the gene therapy drug can be broken down to three parts (layman terms) The missing enzyme, a vector and the capsid. The enzyme that Jonah is missing is called HGSNAT, the enzyme can be man made, the vector is a virus and is the delivery method (like a flu virus) and the capsid is the package around the enzyme and the virus. The virus delivers the enzyme to the cell. The enzyme then does it’s job of breaking down the storage i.e. Hepran Sulfate, the substance that should have been recycled by HGSNAT. Sounds simple right, totally doable.
Once you have designed the drug to perfection, then you have to figure out the very best way to get it into the body. In the case of Sanfilippo syndrome which primarily affects the CNS, getting a virus into the CNS and past the blood brain barrier (BBB) is an extraordinary challenge. The brain protects itself from viruses getting it past the wall i.e. the BBB is a major challenge.
The virus has to be minuscule, but still large enough to carry the drug. In the case of MPSIII C we have an added problem, in that our enzyme can't leave the cell. Most enzymes move around, but HGSNAT is a homebody and attaches itself to the lysosomal of the cell. So we’re planning to go straight into the brain. For the surgery several teeny tiny holes will be drilled into the skull and the serum will be injected in. Sadly I can’t say anymore. One day it will all be published and available to the world. More importantly we will have a TREATMENT for our kids!
Claire, Brian and Ian, the neurosurgeon went out to New Zealand and with a team of vets; performed the surgery’s. That fancy brain software that you all helped us buy, guided Ian in the surgery. Today the sheep brains are back at Manchester, where Brian, Claire and their team are analyzing the vector distribution. Claire, below has the job of slicing the brains of 12 sheep and categorizing the sections then analyzing them. She's the best thing since sliced bread!
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| Claire O'Leary, our postdoc at Manchester, meets P.J. Brooks, NCATS, NIH. ASGCT conference 2017 |
I can’t apologize if this makes you squeamish, we don’t have any other options. This is my life and I want to share it with you. The animals are all free range they are loved by vets and during surgery are given the same respect as a person. They were raised for this single purpose and everyone involved in this process is deeply respectful to the sacrifice that these animals have given, albeit unknowingly made for science; i.e. my son and maybe even yours. FYI I’m pretty sure that Brian likes his dogs more then he does people.
The sheep studies will determine how we will proceed with the clinical trial. We’re almost there, manufacturing the gene therapy will be our next biggest hurdle.
We have done EVERYTHING we set out to do. My ducks are in a row now and it feels good. I’m stretching out and preparing to jump over the “valley of death.”
In a few months we will be launching a few awareness campaigns focused on finding and identifying people with MPSIII. I WILL NEED YOUR HELP!
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| Behind the scenes pic during the filming of Mission: Hide and Help |
The gifts will go to our next benefit Monster Mash
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| This is the best idea Mari has ever had... Well close to it. http://bit.ly/JJBWishlist |
