A few people were fortunate enough to travel to Melbourne at the end of February to attend the first in-person FA Patient Update in what seems like forever! The one in early 2020 was cancelled at short notice and brought home to many of us that the COVID crisis was deadly serious.

Many more of us were able to join via a videolink. But in case you didn’t, the whole thing was recorded and you can view it anytime via this link (password: yB!fCJ2p).

I recommend watching the presentations, and there’s even a “speed” option (bottom right corner) which lets you play at up to 2x actual speed; but I recognise that it can be too much for some people. With that in mind I rewatched on your behalf and here’s a super-brief summary of what’s included;

• (0:03:21) Sherelle Fyfe about fara Australia:

  • Who they are, what they do, how they do it

  • Contributed $310,000 to FA research in fy2021

    • Some projects that have received funding from fara

  • fara Ambassadors (applications to join programme from June)

  • Fundraising

  • Galas (Brisbane was postponed due to the floods, it’s now booked to be on Friday 14th October 2022)

  • www.fara.org.au

• (0:11:48) Martin Delatycki about FA research coordinated through MCRI:

  • Current clinical trials

    • Omaveloxolone – ongoing data submissions to FDA, called a “rolling submission”, to be completed at the end of Q1 2022. Decision making outcome by the FDA later in 2022. If the drug is approved by the FDA , submission for Australia via TGA may follow thereafter.

    • Resveratrol – trial is ongoing, results in late 2022.

    • Vatiquinone – recruitment is complete, (2 year) trial just starting, results expected in 2024.

    • DT-216 – starting its clinical trial journey. Phase I trial (safety assessment only) in coming months. If it is deemed safe, then phase II trial will follow. Eligible participants will be invited to join. NB importance of ensuring your details are up to date in the global registry).

  • Efficacy of rehab in hereditary ataxias – mostly complete (interrupted by covid-19). Expected to finish data collection soon, results in late 2022.

  • Consortium for FA gene therapy readiness – work is ongoing. First (not FA) gene therapy trial in Australia is already underway. It is hoped that first FA gene therapy trial in Australia will be underway late in 2022.

  • Qualitative study to understand awareness of and attitudes to gene therapy almost complete, helping guide development of educational & informational packs for invitation to participate when trial eventuates.

  • Ataxia Instrumented Measure (tool to measure progression of ataxia, based in activities of daily life (ADL), suitable for use with non-ambulatory ataxians) – devices already being used in clinical trials in parallel with FARS.

  • FA Clinical Management Guidelines – comprehensively updated from original published in 2014. Includes new information, evidence, recommendations. Currently being peer-reviewed. Expected to be published via stand-alone website by end of 2022.

  • Australian FA Registry – please make sure Louise Corben (louise.corben@mcri.edu.au) has up to date contact details for you so you can be invited to take part in trials when appropriate.

• (0:34:34) Liz Soragni, Director of Research, FARA USA about FARA-funded research and treatment pipeline:

  • Drug development process

    • When and why FARA funds projects, and how each contributes to the next.

  • Mechanisms by which FARA funds FA research

  • How the process translates into research at every stage where intervention could assist, from genes right to symptoms and life with FA

  • A bit more detail on some drugs in development like:

    • LX2006 – a gene therapy candidate targeting cardiomyopathy, phase 1 / 2 clinical trials due to start in 2022.

    • Gene Targeted Chimeras – small molecules that reverse silencing of FXN gene (so cells in FAers do produce Frataxin). Still at preclinical stage.

    • CTI-1601 – protein replacement therapy (if the cells won’t produce Frataxin maybe we can introduce some and fool the cells into thinking they’re doing it themselves). Clinical development currently on hold following death of an animal in a pre-clinical toxicology study (that’s why they test on animals first).

    • PTC-743 (Vatiquinone) – aims to reduce production of damaging oxidized species within mitochondria – Martin also referred to this trial, beginning now, results expected in 2024.

    • Omaveloxolone (Martin also spoke of this one) – promising clinical trial results not yet sufficient for FDA. More results being submitted as they become available (“rolling submission” mentioned above.

• (0:55:59) Mirella Dottori about gene therapies using FA patient-derived stem cells so they’ll go to the right place and do the right job when the DNA is corrected.

• (1:14:46) Cristina Cortez-Jugo about designing nanoparticles to get inside and do what we want them to do when they get there, inside specific (proprioceptor) cells when they’re carrying corrected DNA during gene therapy.

• (1:28:58) Nellie Georgiou-Karistianis about the TRACK-FA study, a project to get neuroimaging measurements from a large cohort of FAers and non-FAer controls, across the world, across two full years (three measurement points – beginning, middle and end) and across a comprehensive range of aspects. This will help establish a rich, reliable picture of changes that can be expected over time in FAers or non-FAers on all those aspects. These can then be used to set a baseline against which drugs in trial can be evaluated. To understand more of this project, participation criteria and enquire if you’re interested in participating (they’ll cover travel costs) visit: https://www.monash.edu/medicine/trackfa.

• (1:54:53) Ian Harding about a study on neuroinflammation in neurodegenerative diseases:

  • Neuroinflammation occurs in the body normally as part of an immune response and should be protective, activating chemicals within the brain’s neural system to fight and remove “intruders”. It should do its job then return the neural system to a normal non-inflamed state. However, in certain conditions (eg MS, Alzheimer’s, lack of frataxin in FA), it was postulated that this neuroinflammation never calms down, becomes chronic, and itself contributes to cell death or neurodegeneration.

  • The study showed that levels of neuroinflammation are higher in FAers than non-FAers, that these levels are particularly different at early stages of FA development, but that more research will be needed to confirm if a) levels of neuroinflammation follow a predictable path in FAers so could be used as a biomarker to identify if a treatment is working or not and b) if treatment of neuroinflammation directly will have a positive commensurate effect on FA progression.

• (2:02:40) still Ian Harding about two recently launched studies in FA (one of which you might want to participate in if you go to Melbourne to participate in TRACK-FA, the other which all FAers should join):

  • Neuroimaging study (MRI plus other tests) to determine levels of oxidative stress (in FAers).

  • At-home study (via smartphone app) to determine changes in severity over time of FA symptoms.

  • Email harding.lab@monash.edu to express an interest and to find out how to join these.

• (2:11:37) Jarmon Lees about research his group is pursuing using a mini (and he means super tiny mini!) heart grown in a lab from iPS (induced pluripotent stem cells) from an FAer, to isolate FA heart problems and devise solutions. This is important because for more than half of cases where FA causes death directly, it’s caused by heart problems specifically;

  • Blood vessel cells – understanding better why endothelial cells become hardened in FA so blood flows less efficiently through the body and exploring if it might be possible to encourage production of more, healthier endothelial cells.

  • Within blood vessels – understanding why smooth muscle cells reproduce and migrate faster and further in FA, again affecting blood flow efficiency, and exploring how that migration can be controlled.

  • Neurons within the heart – neurons normally release neurotransmitters which regulate the rate at which the heart beats. In FA, neurons release too many neurotransmitters which can cause irregular heartbeat.

  • Cardiomyocytes – regulate calcium waves into and out of cells, another factor in regulating heartbeat. In the FA heart, this process is irregular and the heartbeat is too. How can this process be better managed?

• (2:22:50) Adam Vogel about the process that led to, what’s now involved and what’s next for SpeechATAX, a proven speech therapy programme for ataxians.

  • Previous version was tablet-based and approx. 45 min per session, version in development will be web-based and approx. 30 min per session.

  • Two of the tablets are currently in QLD and available on rotation to FAN members. If you’d like to be added to the user list, please email me (terry@fan.asn.au).

  • Adam also mentioned that SpeechATAX will always be free for FAers.

• (2:40:49) Finish.