Woo! Research update!! One of the super cool things is the number of NKH mice models that are being used at UCL, that Prof. Nick Greene and his team work with.
They now have THREE mice models (more than any other research team) which is phenomenal. They’re all in the GLDC gene, but they are all different in severity. This means they can study different aspects of NKH and see how different treatments work with the different models.
Quick science aside: In every cell in our body, the cells read part of our dna (called genes) and use that as a recipe, make a protein. That protein goes on to do a specific job within the body. In NKH, if the child has a mutation in the GLDC gene, the GLDC protein is broken and the child is unable to process glycine.
The mouse models are designed to mimic NKH – these mice are bred to have mutations in their GLDC genes so they are unable to process glycine, just like our kids. Prof. Nick and his team have three working mouse models:
These Mice have a ‘gene-trap’ – a magic genetic switch that allows the research team to have the GLDC gene either create the GLDC protein, or to turn it off so it doesn’t.
When it’s off, these mice have NKH and present very similar symptoms like our kids do. They have higher levels of glycine in their blood, urine and body tissues, and about half the mice live for approximately 3 months. In the liver, they have perhaps 10% functionality of the GLDC protein (someone who doesn’t have NKH would have 100%).
The bonus of being able to turn the gene trap on and off is so they can understand how the glycine cleavage system works in different places in the body. It also means that if they turn it on (so the mice a producing the GLDC protein correctly), they can simulate what effect a working treatment might have.
(Side note: don’t be intimidated by the name. GLDC is the name of the gene. GT presumably stands for genetrap, and because they have 2 and this is the first, there is a 1 on the end)
This is another gene trap mouse model (where they can turn the gene on and off), but this one completely prevents all GLDC gene expression (0% functionality of the GLDC protein). Very few mice survive after birth – this is a more severe model than the previous model.
By having a model that doesn’t produce any of the GLDC protein, they can see what the biochemical and metabolic effects are. This is huge for understanding what NKH does, and how it works.
Gldc missense mutation
The team were able to create a model that has a missense mutation – a mutation that changes one ingredient in the NKH recipe (imagine replacing sugar with salt in a cake recipe, for example. The cake can no longer do its job of being delicious. Similarly, if the recipe for the GLDC protein is wrong, it can’t do its job processing glycine).
This is very similar to the kind of mutation a lot of NKH kids have. In fact, this is a known mutation, there are children with NKH who have this exact mutation!
This model is used to test treatment options, and to better understand NKH progression. This is also huge, because if a treatment option works well with this model, there is a chance it would also work well with our kids.
When I spoke to Nick last he said we know more about NKH now than we ever have before, and a lot of that is because of these models.
You guys, were so lucky to have Nick and his team on our side! He’s literally so far ahead of everyone else (side note: he’s already three years into gene replacement therapy research using these mouse models. I know the Drake Rayden Foundation are fundraising right now to kick off the exact same research that Nick’s already done.)
For everyone that supports #teamMikaere and Joseph’s Goal – this is where your money goes. This is where the life changing research is happening. This is where change is happening. So thank you, thank you thank you to everyone who has ever donated, bought a book or a tshirt or made a justgiving page! You guys are the best!
PS – The Charity Fun run is happening on the 28th of September in London. Looking for both runners and volunteers! More at www.nkhcharityrun.com 🙂