Build Log 003
As a reminder, I am working on a kidney regeneration idea that aims to halt, and potentially reverse kidney disease. You can read more about it here.
Where have I been?
As mentioned in my last build log (Jan 14), I had been interviewing with different labs to gain some research skills. I eventually got a position doing molecular biology, but it required all my focus for the first two months (as I am completely new to this field). Now that my training has settled, I have more time to devote to my independent research.
Basically, I am sorry for ghosting, but it was necessary!
What have I been up to?
Doing molecular biology! I’ve been working as a research assistant in a neurology & immunology lab, where I have been doing a lot of molecular biology, learning immunology techniques, cell culture work and general designing of experiments. I chose to work in a lab “unrelated” to my (kidney) field for the following reasons:
I wanted to avoid the dogma of current thinking around kidney regeneration
I did not want to limit myself to only learning techniques based on my initial idea (I may pivot, which I indeed did!)
Being around great scientist was more important to me than being in the most “relevant” field
The wet lab technical skills are very transferable (This will become clearer in my next build log)
The institute I am at has a lot of training opportunities outside of this field
I have also been narrowing my focus in terms of the specific type of kidney disease that I will be starting with. After a bit of exploring I decided to go back to what I know i.e focus on my own type of kidney disease - collapsing focal segmental glomerulosclerosis (cFSGS).
In a surprising turn of events*, it turns out that I have the APOL1 genetic mutations that significantly increase the likelihood of a person developing kidney disease, specifically FSGS (with viral infection and/or autoimmune diseases being thought to be the trigger of this mutation). So I narrowed my focus further to individuals like me who have some viral infection or autoimmune disease, coupled with the double APOL1 genetic mutation. In my case it is a rheumatoid arthritis condition called Still’s disease.
What has changed and why?
Initially I was focused on complete external organ regeneration that would happen outside of the body, with the aim of transplanting it into the user. Here is a timeline of all the ideas I have gone through
Decellularized pig organs. Strip the cells of a pig organ and then replace them with the person’s own cells to create a fully functioning organ that does not require immunosuppressants. I decided against this because:
It wasn’t entirely clear to me that such an organ would not cause an immune response from its host, which was one of my priorities when deciding on a solution that would increase my quality of life
Given the large number of specialized kidney cells, getting that many types of cells to differentiate and adhere to a foreign scaffold seemed like it required significant research and development before being able to get anything in clinical trials, talk less of in the market, in the next 5 years
Focusing on users** with end stage renal failure seemed too hard. At that point the user has multiple problems, and trying to solve them all at once seemed like a herculean task to tackle if the goal was to see this tested in humans in the next 5 years.
It did not really align well with my idea of a solution that solved both the users health issue, whilst providing a really excellent user experience. An excellent user experience being one that doesn’t require them to think daily about their condition, disrupts their day to day life and has a short turnaround time between diagnosis and treatment. I will probably go into what a bad vs good healthcare experience looks like to me in another post.
And honestly, I just did not have a good gut feeling about this.
Nephron transplant. The thinking here was that I should shift my focus to people with stage 2-4 kidney disease, as at this point other kidney functions are usually intact, with the main issue just being filtering waste measured via eGFR. I explored sourcing nephrons from either pigs (and performing decell-recell on them) or growing them from scratch (building on top of organoid capabilities). I decided against this because:
It didn’t seem like a long lasting solution that would make a big enough impact in the users life. After modeling the nephron units as multiple electrical circuits in parallel, I wasn't convinced that adding a few nephrons would have any serious impact. It also became clear to me that it actually takes a significant loss of nephrons before a drop in eGFR is actually noticed, as the kidney does a pretty good job of having neighboring nephrons compensate for such losses. I also confirmed this by modeling nephrons as electrical circuits in parallel.
If I am being completely frank, I also just had another gut feeling that this was not the right direction to head in in terms of what I considered success, although I felt this solution was better than the previous idea.
Glomeruli transplant. After whittling down my initial user base to people with FSGS, I briefly explored either replacing or adding an additional glomeruli to an already established nephron unit. The hypothesis was that in the early stages of FSGS only the glomeruli is damaged, with the tubules and blood vessel network still intact. I was considering utilizing the rest of the nephron unit with an additional or replacement glomeruli.
Ultimately I decided against this idea for similar reasons to the above. Focusing on users such as myself, such a transplant would not give me peace of mind, as it would be dependent on me getting diagnosed at exactly the right time, which is dependent on having the right tools (which we currently do not have) and also the right healthcare infrastructure (getting an early diagnosis in the NHS is extremely difficult as most doctors err on the side of always wanting to “wait and see” until there is unequivocal evidence that x is the cause of your symptoms.)
My focus moving forward
There were common themes amongst all the ideas that I explored that did not sit right with me:
Work on the users end to know exactly when to engage with the healthcare system (people are lazy and will usually go when things are clearly very bad, which by then is too late)
Dependence on doctors taking action on time (like I said most doctors' response to vague symptoms are “wait & see”. More importantly, doctors are human , which means that there are a lot of reasons why on any given day they may have unfortunately misdiagnosed you)
Lack of peace of mind before and after diagnosis
Dependence on a fast turn around time between the time the user feels there may be something wrong and the time they receive treatment (again, if you are in the NHS or any form of public healthcare you are to expect generally long waiting times)
A transplant seemed like a quick fix that did not address the fact that I will always be more likely to experience kidney damage due to my genetic mutation + autoimmune disease. There are only so many transplants I can have!
I realized that I just really disliked the fact that the kidney was not a self repairing organ, which caused me to shift my question - why couldn’t the kidney be a self repairing organ?
Where I am at now
So that’s what I am exploring now - ways to make the kidney a self repairing organ. I will go into this more in my next build log, along with a more detailed review of who my initial target user is (underlying mechanisms & that sort of thing) and my first set of experiments (yay).
*As some of you may remember, I am currently a co-investigator on the APOL1 project at King’s which studies the relationship between this gene mutation and autoimmune disease to understand why & how it causes kidney failure - it seems as though the dots are starting to connect!
**Moving forward I will be using the term “users” as I really hate the concept of a patient and being treated as such.
If you have gotten this far, thanks for reading - I appreciate it! If you have any questions, feedback, or just want to chat about what I am doing, you can reach out to me via email adaobiadibe23@gmail.com