A Rebel Alliance

No, I'm not talking Star Wars. 

I'm talking parents of rare children. Specifically, I'm sharing an update on the PIGN-CDG drug-repurposing project. If you don't have time to read much, then check out this update from Perlara: Research Update. If you have more time, continue on.

As you may be aware from prior posts, our rare community is researching whether existing known drugs or compounds could be beneficial in helping our PIGN children. You can read more about the initial scope of the project here: Drug Repurposing Fundraising Many of you have generously donated directly or supported AJ's fundraisers selling fidgets and dragons that he creates himself on our 3-D printer. (You can still donate directly here: Tax-Deductible Donation or order dragons/fidgets here: AJ's Fundraiser)

To greatly simplify PIGN-CDG, Teddy's body cannot process sugars on the most basic cellular level. If you recall sugar chains and cell processing from biology, well, kudos to you because I don't. But you can think of it like an assembly line in a factory that has a broken part that prevents most of the pieces from being perfectly assembled. They may be somewhat functional, but it's rare (no pun intended) that they are fully functional. This results in all the challenges our children face, from seizures to hypotonia to respiratory challenges to developmental delays and the list continues. Their bodies don't function right on the cellular level, which obviously impacts them as a whole. 

It doesn't stop Ted from enjoying flying fighter jets, though.

This also complicates potential treatments because all medications and treatments can be impacted as well by these faulty sugar chains and processing problems. Everything can be a bit (or a lot) off with our children. Combine that with the fact that there are approximately 100 known cases of PIGN-CDG, and well, it's understandable why there's no treatment for this disorder. We can only treat the individual symptoms (aka treat the seizures, manage the hypotonia, etc.) and do nothing to improve the overall health of our children. 

That's why this drug-repurposing project is invaluable. This ground-breaking scientific research is taking a huge bank of known medications and compounds to see if anything that already exists could be used to improve the overall health. This is a long, expensive process. 

But it's so exciting that we're seeing promising results. As Perlara's update shares, some families have been piloting ascorbyl palmitate and seeing improvements. This compound can be easily accessed without a prescription in many countries, though each family must still work through their medical team. We are a bit later to start due to the events of last year, but we have baseline labs scheduled in a week with a bottle of ascorbyl palmitate secured. (Hmm, that reminds me we need to take baseline videos of Teddy this weekend.) We will start him at a low dose for a month, monitor and recheck labs and then potentially increase his dose. 

While we don't anticipate any overnight, drastic changes, any improvements for our PIGN children are huge. You may read the research update and think, well, that's just normal developmental milestones - it could be just that the child is getting older and advancing. But our children don't follow normal milestones, and they lag months or years behind most, if they achieve them. So any progress noted in a couple months of trialing the compound is fairly reasonably associated with the compound (though we will leave that up to the scientists and doctors with baseline and other labs, video evidence, recorded seizures, etc.)

We're excited about what this could mean for Teddy. We're excited about what it could mean for all our PIGN families, both present and those who get this difficult diagnosis in the future. So the next steps, while we continue to fundraise, is that because it's an over-the-counter compound, we're able to pilot and trial on our own as families (similar to how we've fundraised) without FDA approval. Perlara is busy in the lab and will be testing the best hits, including this ascorbyl palmitate, on the DNA samples from various PIGN children, including Teddy. This is the next step to evaluate what works best with real human PIGN mutations (of which there are many). The hope is that we continue to make progress and do move to the point of FDA trails, whether for this compound we have now or something different. 

The science will take years, and we so appreciate your generosity and support. It's exciting (and expensive) to be at the forefront of medical and scientific research that will directly benefit others like Teddy.

PIGN Research Project Update

I wanted to share an exciting update regarding the PIGN drug repurposing project. I shared about the project previously on the blog here. For those unfamiliar, the quick explanation is that our PIGN community is fundraising to do the scientific work to determine if any existing drugs can be used to treat those with PIGN-CDG. It's a long, expensive process, but this scientific method has been successful with other illnesses or disorders, including very promising results with another type of CDG. Essentially, it's the best hope we have for any type of true treatment for PIGN in the foreseeable future.

To do this research, 10 genetic variants were selected to build yeast avatars to test against existing medications. These variants represented a wide range of the known PIGN defects and were selected to represent a wide range of defects and because they were easily modeled in yeast cells. We knew Teddy's variant wouldn't be selected because it's not easily replicated due to part of his variant being a splice site, meaning his gene split apart and reattached in the wrong place. (Whoops, he inherited that from me.)

Additional variants were selected to be part of a second phase of research. That group of variants will be used to test the drugs selected against human cells, as opposed to yeast avatars. Teddy was selected to be a part of this research group, as it's simply growing cultures of his cells to test the different medications.

This meant Teddy needed a skin biopsy done. He's had this procedure done several years ago, as part of his NIH natural histories study, but he was sedated because other tests were done at that time. This time required several weeks of coordination with Mayo Clinic and local providers leading up to the actual appointment.

He had his biopsy done Monday, and it went remarkably well all things considered. (All things include the fact that it required 3 of us to restrain him while the puncture was done, and there's a whole separate saga about hives, urgent care visits and the like that occurred later in the day.) 

Teddy had a lot of opinions on where I should sit throughout his appointment.

So his sample is being sent to Mayo Clinic for storage. His cells will be replicated in laboratories to test against different medications. The goal is to see if a medication that works well in multiple yeast avatars works well in the human cells, along with testing a wider range of mutations. (Unfortunately unlike something like Down's syndrome where the mutation is universal, CDG-PIGN encompasses a wide range of mutations, many similar but relatively few completely identical.)

While it was tough to have Teddy endure a skin biopsy that's technically not needed for diagnosis or treatment at this time, we recognize this act can benefit not only potentially Teddy but hundreds of other families with this disorder down the road. It's a small sacrifice to benefit the greater good. (And as we already lost another one of our PIGN kiddos this year ... it's January 18 ... it's the least we can do.)

We'll be continuing to fundraise as science isn't cheap, and this is very much a grassroots campaign done by the families affected. We're small, but mighty when combined with caring friends, family and those who support our journeys. 

If you want to make a donation, you can do so here: https://teddystriumphs.blogspot.com/2022/06/pign-cdg-research-were-fundraising.html