What I learned at FARA’s Scientific Symposium

I’m not a scientist, nor a medical researcher. I’m just a normal FAer. I was invited to the Symposium as part of a Patients Panel, a Q&A session for researchers who might work in a lab and might interact only with FA cells, to meet and understand real FAers, the people who’ll benefit most directly from their work. (Subsequently all the FAers on the panel, including me and Samantha Dwyer from FAN, were invited to become FA Ambassadors for FARA – more on that later).

To be there was humbling but rewarding. It’s amazing to appreciate the range of brilliant minds, all approaching the challenges of FA from different perspectives. There was much detail I couldn’t hope to understand, but I understood the wide range of areas they were working in or on.

So, forgive me for what I just didn’t understand. Here’s a summary of what I think I did:

The thing we probably all know about FA is that it’s genetic. What I’m always impressed by is how the explanations seem so straightforward. Here’s a distillation of what I understand from all I’ve been told or have read: “Your gene is like an instruction book within each cell and the result is production of protein appropriate to that cell’s function. The problem in FA is that there’s an expansion of a repeated sequence (GAAGAAGAA) at one point on the FA gene (FXN) and that causes confusion like if a single page in an instruction manual was there 1,000 times over and you had to read every page before doing a job”. If the problem’s so well understood, might the solution be easy to find?

Unfortunately, it’s not that simple. Our genes are in the nucleus of every cell in our bodies and each of us has as many cells in us as there are stars in the universe. And some genes are turned on and others are turned off in different kinds of cells, which is what makes them bone cells, heart cells etc. If we change (correct) a gene in one cell, we want to be sure that the change occurs in all the cells of that type.

There is one branch of work being done to reverse-engineer adult cells back to stem cells. Then, if a way can be found to correct the gene problem in these cells, they can be directed again to specific types like heart, cerebellum, dorsal root ganglia etc., basically the parts where FA impacts most severely.

Do you remember the original Ghostbusters movie? Early on Dr Spengler says they should “never cross the streams” of whatever comes out of their guns. At the climax of the movie he shouts that that’s exactly what they should do. Well there was a presentation about fixing FA genes which included something about reversing polarity that reminded me strongly of that. It was mostly about viruses though. The polarity bit seemed to be about the new instruction page that will replace the repeated pages that are the FA problem.

The presentation was about identifying the right virus to carry this repair kit into the cells. Viruses are pretty good at doing this (after removal of their dodgy bits) but in many cases the body spots them and the immune system gears up to do its antiviral stuff. In a few experimental cases things pushed too fast with fatal consequences so progress now is slow and very careful. The most recent and promising route involves AAVs which are so small they don’t provoke immune responses from the body. They’re very simple viruses though, tending to deliver their payload then die off so whatever they’re given to carry and deliver must be perfect and work first time.

When they’re doing test drives of stuff like this they include also a gene alteration that’ll make the impacted cell glow phosphorescent green and I’m left with an image in my mind of a whole human organ glowing solid green. Key take-out: it looks like they’ve identified the right tiny virus and the right instruction book alterations. They’re getting close to identifying a cure for FA (although there’s still lots of work to be done to make sure there aren’t unintended consequences).

To impress upon us the breadth of exploratory routes there was a presentation even from a plant guy. A plant guy? you ask. Yes I say. As you probably know, FA is caused by a GAA repeat expansion on the FXN gene. Now they’ve identified a plant which has developmental issues due to a genetic problem and looking more closely they’ve identified that it’s a triplet repeat. It’s less dangerous and more easily monitored to explore ways to fix this problem in the plant. If and when a solution is found it won’t be immediately applicable to FA as it’s a different gene but it’s bound to raise important suggestions to explore.

It’s always been said to me that FA involves neuromuscular degeneration but there’s no impact on cognitive ability. Results were presented from a study that says it’s not so simple. Potentially most exciting to the scientists with machines that can measure this stuff is that over time, with FA progression, there are measurable changes in brain volume, most notably in “white matter”. What I found equally if not more important were results from a separate study that suggests FAers might be using their brains differently than non-FAers. Hence, while there might be measurable physical changes in the brain over time, it seems likely that brain plasticity is causing FAers to change how the remaining brain is used, to compensate.

Another presentation relevant mostly to specialists with access to big machines was about a way to more effectively monitor the heart as FA progresses. More than 50% of FA deaths are due to heart problems and most FAers have cardiomyopathy (thickening of the heart wall) so while I didn’t understand the specifics I want my cardiologist to be aware of this presentation before I have my annual echocardiogram.

Two studies were presented about rehabilitation, one about speech, the other about physiotherapy and they both had similar findings – intensive therapy over a short period leads to significant improvement. Next step is to design a way for an intensive programme to be delivered/monitored and then how a less intensive maintenance programme can be designed for ongoing use (the other 11 months of the year).

Another study looked at the personality, social skills and psychological health of FAers compared with non-FAers. It comes as no surprise to me that FAers were found to show more symptoms of depression, stress and negative social behaviours. My personal view though is that in matters like this it might be more accurate to evaluate someone’s life with FA rather than draw conclusions about FAer vs. non-FAer. I’m reminded of a report from some time ago that revealed that people with disabilities rated their quality of life higher than people without, and explored the assumption the opposite would be true (contact me for more info on this).

In summary then, there’s an enormous amount of research going on in FA right now, and exciting progress is being made toward finding a cure. Research is also going on into how we can monitor, maintain and even improve our health in the meantime. My favourite Ron Bartek (head of FARA in the US) quote is “there’s never been a better time to be a sick mouse” but in reality, there’s never been a more exciting time to be an FAer!

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