fara Australia Patient & Family Information Forum, part 5 of 5
On Feb 29th, 2024 fara gathered the leading FA researchers in the country, brought them to Brisbane and held a forum at UQCCR for them to tell us about their work. I was lucky enough to attend those presentations, but having rewatched them, I realise that I missed much that was presented at the time. Fortunately fara organised for them all to be recorded and you can view them in your own time at https://www.fara.org.au/news/watch-all-presentations-from-our-recent-patient-and-families-information-forum. Alternatively, you can read my summaries of what was presented (four previously, and the final one below); or check out both video and write-up and let me know if you think I’ve done a good job!
I’ve previously written a note summarising presentations from Ian Harding, Mirella Dottori, John O’Sullivan, Monique Bueno-Alves, Lucas Tocchini, Liz Soragni, Martin Delatycki, Amy Hulme and Rucha Sarwade. You can find them HERE, HERE, HERE and HERE.
The final presentations were from Louise Corben, Nellie Georgiou-Karistianis and a wrap-up from Brad Hyde.
If you asked any FAer who’d had contact with the Melbourne FA Clinic over the past several years, they’d tell you the person who’d know about everything happening in the FA research space in Australia (as well as all about the Melbourne Clinic) was Louise Corben. In the past year Louise handed coordination of the Melbourne FA Clinic to (FAN friend – past AGM presenter) Sarah Milne so she could focus more closely on specific research projects and told about some of them:
1. Clinical outcome measures
2. AIMS – Ataxia Instrumented Measures
3. Measuring ataxia in children with FA
4. Natural History Studies (FA GCC and UNIFAI)
5. Readiness for FA gene therapy trials
I’ve spoken earlier about Skyclarys becoming the first approved drug ever for FA by the FDA in America, a process now being progressed for Australia through the TGA. Well critical to obtaining that approval is being able to demonstrate results from a trial showing that participants who took the drug had a significantly different outcome on something measurable, than participants who didn’t. Skyclarys had difficulty with the FDA in America because of those outcome measures.
The challenges are huge. FA is a degenerative condition that affects everyone differently. So what outcome measure should you pick, what outcomes can you define (because you must define them before the trial for it to have validity) that would have been expected without the drug, so they’re significantly different with it? The science bit is usually straightforward. Medical researchers know what effect they seek from their drug. What their trial must demonstrate though, is not just whether that chemical result has been achieved, but how it’s translated into a benefit in the lives of people they’re treating.
Measures that are universally accepted and relatively straightforward to measure (incl. scales like FARS, mFARS, SARA) often involve balance and walking, but FA is a progressive condition and upwards of half of known FA sufferers are wheelchair-bound. Defining your outcome measures in terms of balance or walking limits the expectations of your treatment to early after presentation/diagnosis (probably not great for you, certainly not great for half of known FAers) and limits the number of trial participants available to you.
Louise has been closely involved in development and validation of a potential solution to this problem – the Ataxia Instrumented Measurement (AIM) system. The system uses a number of devices that measure movement and balance of a participant during simulated eating and drinking tasks. An individual’s balance and an eating or drinking tool’s path can be plotted in 3D and a score given based on the jerkiness, the speed, the accuracy of the movement etc., of both the individual being assessed and the tool; and it’s been shown that this reflects accurately the severity of someone’s FA. And it can be used by almost all FAers.
This system is already being used in a number of FA clinical trials and natural history studies.
Going back just a little to the problem of partipant numbers in trials being limited because outcome measures couldn’t be validated with them, that problem is deepened because children can’t be included in trials. Many will know that the area of the brain most impacted by FA is the cerebellum which is involved with balance and motor control. The cerebellum doesn’t finish developing in anyone until about age 12 onwards so when kids are assessed with any of the established FA rating scales, they frequently give results that can’t be clearly differentiated FAer vs. non-FAer, simply because they’re kids; they move like kids, they fidget like kids.
So Louise’s team are working on two things with AIM – 1. They’re reworking the algorithm to redefine the baseline more specially for non-FAer children and 2. They’re developing new tasks and things to be measured which can feel less like tests and fit more naturally into the course of everyday life. It’s hoped that with the combination of these two changes, AIM can be validated as an outcome measurement tool for kids with FA.
The next thing Louise told us about was the FA Global Clinical Consortium (FA GCC). I often tell people that one of the (few) advantages of FA being as rare as it is, is that the research community is so strongly networked. Most of the researchers know one another and most research funding is channelled through a single source (FARA in the USA). An important recent development in this regard is the establishment of the FA GCC. It means that natural history information and research data can be shared easily and used anywhere that’s a member. This cooperation has proven invaluable already in helping make the case for Skyclarys approval to the FDA.
Louise told us about the existence of the Australian Friedreich Ataxia Stem Cell and Gene Therapy Consortium. This is a group based at MCRI in Melbourne who are making preparations for Australia to be able to host a gene therapy trial whenever an opportunity arises. They have an advisory board with some of the leading FA researchers in the country. And they work closely with the International Consortium for FA Gene Therapy Readiness.
A gene therapy trial in FA is already underway in America by Lexeo Pharmaceuticals, and more will follow. This group works together to ensure that a similar level of preparedness (operations manuals, protocols etc.) will exist when an opportunity arises for a gene therapy trial to be run in other locations too, both elsewhere in the USA and in other countries around the world.
An example of that preparatory work is a research study led by the Australian group to explore attitudes, expectations and desires of FAers and their carers to gene therapy trials. And it produced several important findings:
To FAers the most important targets are neurological (balance, speech etc.) (whereas medical researchers often prioritise the heart).
Trials should aim to include FAers at all stages of progression (reinforces the importance of defining outcome measures that don’t limit who can participate in a trial)
Concerns were raised about including children in trials due to the permanence of gene therapy
A decision to participate in any trial tends to be based on risk vs. reward. Due to the permanence of gene therapy, the chances of it making a participant’s condition worse weighs heavily in this calculation.
And these results highlighted the need for further research with potential trial participants to understand these risk vs. reward considerations more deeply and also to re-evaluate what should be communicated in order to obtain informed consent from trial participants.
Quick promo: We’re ever so grateful to Louise for coordinating the collection of information to update the globally recommended FA Clinical Management Guidelines (more on that under Managing FA/What your GP should know).
After Louise came Professor Nellie Georgiou-Karistianis who’s worked closely with Ian Harding (also Louise, Martin and many others) to develop and coordinate the TRACK-FA Study. Nellie gave us a snapshot of what the study’s about and what results they’re seeing after only a single baseline year.
As background, consider that Nellie’s heritage is Greek and they don’t like to do things on a small scale. I imagine one day saying of Nellie, similarly to what they said of Alexander, her ancestor, that she’ll weep because there’s nothing left to test!
Some time back, Nellie and the team identified that many tests done on FAers weren’t much use beyond their specific, often very narrow design, and they set out to design a study that would change that. The TRACK-FA Study measures many many things, for a huge group of FAers including very young FAers (and lots of non-FAer control participants too), according to the same testing protocols, in sites across the world. It’ll run over at least three years (baseline, +12 and +24 months). It’ll test the brain, blood, spinal cord imagery, cognition and more, for every subject, so change can be determined as well as rates of change in key measures, if those measures change at similar rates to each other, whether they differ based on GAA repeat numbers, by age, as FA progresses, and if any change for other reasons.
Whenever someone says to you that they “had an MRI scan” you should ask them which one. An MRI scanner can be used to provide different imagery to show different things, and participants in the TRACK-FA study spend more than an hour inside the scanner because the study checks lots of them.
So far, the results of the baseline testing are in, and at this stage the results demonstrate significant differences between FAers and non-FAers. As the study progresses, it’ll be tracked if and by how much those differences change over time, and also changes and rate of change can be tracked between the same participants across measures and correlations identified or ruled out.
The day was wrapped up by Brad Hyde who gave us a quick update on how fara’s going (income in fy23 was almost back to pre-COVID level but fara’s struggling as everyone else is, in the current cost-of-living crisis).
This has meant fara could contribute funding to four new FA research projects and extend three others. In the last five years fara has distributed more than $1,000,000 in research funding and what’s been presented today is what that funding leads to. Every time you participate in any fara fundraising event, it shouldn’t be an intangible “FA fundraiser”. This work is what it’s for!
Brad talked us through some highlights of the fundraising year including callouts to QLD champions Purple Rhane Designs (https://www.purplerhane.com.au/) and Rare by Brooklyn (https://www.instagram.com/rarebybrooklyn/) who each make regular contributions that are very welcome!
This is the fifth and final one of these write-ups. Please comment below if you find them useful and have comments about any of the research underway. From next time it’ll be back to thoughts and commentary on life, from an FAer, or at least until the next FA research update. Look out for the next post soon enough.