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The Friedreich’s Ataxia Alliance at Oxford Bulletin - June 2022

Welcome to the FA Alliance at Oxford’s June Bulletin. Please read on for FA Alliance at Oxford updates, the latest news, upcoming events, funding opportunities, clinical trial updates and to meet our Investigator and Ataxian of the bulletin!

FA Alliance at Oxford Updates

FA Alliance at Oxford Website

Work has begun to develop content for an FA Alliance at Oxford website. The page will be hosted on the existing Oxford-Harrington Rare Disease Centre website. We’ll let you know when the site is live. If you have any suggestions for content for the site, please do get in touch with Geoff.

FA Alliance at Oxford Year 2 Plans

We are extremely grateful to EndFA for committing to continue to fund the FA Alliance at Oxford for another year. We are planning further events to bring the Alliance together, introducing new members to the Alliance and funding projects in investigators’ laboratories.

News

Webinar Recording for Generating Synthetic Longitudinal Data

In this webinar, Replica Analytics' Dr. Khaled El Emam is joined by Critical Path Institute’s Director of Data Science Lucy Mosquera to provide a general introduction to synthetic data generation, explaining what it means, how it works and what technologies are used, as well as an overview of the use cases where synthetic data can provide value in the context of real-world data and clinical trial data in collaboration with C-Path. Watch the webinar here.

FARA Flash Talks

Throughout May, FARA hosted a series of weekly flash talks from FARA-funded young investigators from across the world. The full playlist of talks can now be viewed here.

FARA Newly Awarded Research Grants

Award for Innovative Mindset

Manuela Corti, PhD and Tanja Taivassalo, PhD - University of Florida

“Functional electrical stimulation (FES) cycling training to improve motor and cardiac functions in patients with Friedreich’s Ataxia: a feasibility and efficacy study”.

Events

Ataxia Global Initiative Young Investigator Initiative Webinar Series

The Ataxia Global Initiative (AGI) is holding a webinar series called Young Investigator Initiative (YII). To view past webinars and register for upcoming ones, click here.

Oxford Metabolic Health Symposium

The OMH Symposium will take place on Friday 1 July 2022 at the Medical Sciences Teaching Centre, South Parks Road, Oxford. More details and the registration form are available on the OMH website.

Muscular Dystrophy UK Oxford Neuromuscular Centre Annual Meeting

This year’s meeting will take place on Thursday 14 July at the Saïd Business School. You can register via Eventbrite.

Oxford-Harrington Rare Disease Centre Symposium Save the Date, Sept 13-15 2022

Oxford-Harrington Rare Disease Centre’s Rare Disease Symposium is to be held from early evening 13 Sept to 15 Sept at Pembroke College, Oxford. The focus will be on new research initiatives and cutting-edge technologies from leading scientists in academia and industry that will benefit rare disease research and accelerate the development of new treatments. Further information will be circulated in due course.

International Congress for Ataxia Research, Nov 1-4 2022

November 1-4 2022, Renaissance Dallas Addison Hotel, Dallas, Texas, USA. Abstract submission is now closed. For more information and to register, visit here.

Ataxia Global Initiative Conference, Nov 4-5 2022

The Ataxia Global Initiative (AGI) conference will take place on November 4th & 5th at The Renaissance Dallas Addison Hotel in Dallas, Texas, USA, directly following the International Congress for Ataxia Research (ICAR). The AGI Conference brings together academia, industry as well as patient advocacy organizations and will focus on trial-readiness for Ataxias. Delegates may be interested in attending both conferences as they are distinct and complimentary to each other.

A preliminary program and general information about the AGI Conference 2022 is available here.

RNA at the Bench and Bedside III

November 8-10 2022, Carlsbad, CA, USA and streamed virtually. More information here.

Funding Opportunities

FARA General Research Grants, Postdoctoral Research Award and Postdoctoral Fellowship Next Letter of Intent Deadline is August 15 2022

For further information on FARA’s grants program, visit here.

FARA indicated after our first FA Alliance at Oxford Workshop event they are happy to receive bullet point project proposals from FA Alliance investigators to receive some early feedback on their proposals. Contact Geoff if you need to be put in contact with our colleagues at FARA.

Harrington UK Rare Disease Call 2022

Modelled after its US programs, this scholar award provides UK researchers with a unique opportunity for funding and personalised discovery and development support to advance promising research into novel treatments for rare disease. The call opened on June 13 2022 and the deadline for Letters of Intent is July 18 2022. Further details are available here.

MRC Developmental Pathway Funding Scheme

Apply for funding to develop and test novel therapeutics, medical devices, diagnostics and other interventions. Opening date is June 10 2022, closing date is July 20 2022. More information is available here.

The Translational Research Office have requested you contact them as soon as possible to get the best out of their support service for applying to this scheme.

French Friedreich’s Ataxia Association Grants

In order to stimulate research and studies on Friedreich's Ataxia, the French Friedreich's Ataxia Association (A.F.A.F.) will be offering grants of up to 30.000 €/year/project, for a maximum of two years. The grants are expected to be awarded in November 2022.

Application forms are available by contacting A.F.A.F. For more information click here.

The application deadline is August 26 2022.

National Ataxia Foundation Opportunities

The next call for grant applications will open July 6 2022. More info and eligibility details are available here.

Clinical Trials and Therapeutic Development Updates

Reata Pharmaceuticals Announces FDA Filing Acceptance and Priority Review Designation for the NDA for Omaveloxolone

Reata Pharmaceuticals has announced the U.S. Food and Drug Administration (FDA) has accepted for filing and granted Priority Review of its New Drug Application (NDA) for omaveloxolone for the treatment of patients with Friedreich’s ataxia. The NDA is supported by efficacy and safety data from the MOXIe Part 1, Part 2, and MOXIe Extension studies.

About Omaveloxolone

Omaveloxolone is an investigational, oral, once-daily, activator of Nrf2, a transcription factor that induces molecular pathways that promote the resolution of inflammation by restoring mitochondrial function, reducing oxidative stress, and inhibiting pro-inflammatory signaling.

Read the full press release here.

LEXEO to start phase I/II clinical trial for patients with FA cardiomyopathy

LEXEO Therapeutics plans to launch a phase I/II clinical trial of its adeno-associated virus-based therapy designed to intravenously deliver a functional frataxin gene for the treatment of Friedreich’s ataxia (FA) cardiomyopathy this year. At the recent American Society of Gene & Cell Therapy annual meeting in Washington, DC Lexeo presented new preclinical data supporting its FA cardiomyopathy program.

About LX2006

LX2006 is an AAV-based gene therapy candidate delivered intravenously for the treatment of FA cardiomyopathy, the most common cause of mortality in patients with Friedreich’s ataxia. LX2006 is designed to target the cardiac manifestations of FA by delivering a functional frataxin gene to promote the expression of the frataxin protein and restore mitochondrial function in myocardial cells. In preclinical studies, LX2006 reversed the cardiac abnormalities in FA disease models and showed improvement in cardiac function and survival while demonstrating a favourable safety profile.

Investigator of the Bulletin

Briefly describe the work that happens in your lab.

My lab is interested in the biology of unusual nucleic acid structures called R-loops. These structures are formed in all living organisms during transcription but they are also mis-regulated in human diseases, including neurodegeneration and cancer. My group was the first to show the association between R-loops and FA. We are interested to understand what these pathological structures do in FA and how we can stop their toxic behaviour. My lab also develops tools to study R-loops and R-loop-associated proteins, helping us to understand the molecular mechanisms of FA. In particular, we have designed methods to map R-loop locations in human cells and uncovered and characterised multiple R-loop-interacting factors.

What’s the most recent, exciting experiment that you’ve seen performed in your lab?

Recently we have shown that the stability of R-loops is controlled by RNA modifications, including m6A RNA modification. This is important, because the stability of R-loops is different in physiological and pathological conditions. We think that modifying the stability of R-loops can be a tool to overcome their damaging effects in diseases. We are currently testing these ideas in the lab.

What excites you and motivates you to work on Friedreich’s Ataxia?

FA is a devastating neurodegenerative disorder and there is no current therapeutic interventions to treat it. Even though the genetic cause of FA was discovered in 1996, we still do not fully understand its underlying molecular cause, representing a major challenge in development of efficient FA therapies. I believe my group is in a strong position to utilise our expertise in gene regulation and RNA biology to uncover the molecular mechanisms of FA. Being funded by Ataxia UK and NAF (USA) to do our research, my group has met many FA patients over the years, who have been strong, supportive and inspiring. We do our research to help these people.

What do you hope the FA Alliance at Oxford can achieve?

The FA Alliance at Oxford is a fantastic opportunity to bring together groups working on FA. University of Oxford hosts multiple talented researchers and there is no doubt in my mind that this powerful combination of top scientists will be able to move FA research towards successful therapeutic interventions for this disease. Oxford scientists have proved to be extremely successful in coming up with therapeutic interventions for Covid-19, therefore, I don’t see why this cannot happen for FA.

Ataxian of the Bulletin

I have been involved with Ataxia UK in one capacity or another since I took medical retirement from a successful career in local government. I am an ambassador for Ataxia UK, after having served as a trustee for the charity for eight years. I was the chair of the trustees for the last two years during the COVID-19 pandemic. I helped establish the Birmingham branch of Ataxia UK and have been involved in running all aspects of the charity and its events. I run the workshop at the annual conference for people newly diagnosed with ataxia to help educate them about what ataxia is and how it can affect you and what you can do to help yourself. Alongside volunteering, my other passion is writing, and I publish a blog at www.worldaccordingtome.blog and am currently writing an autobiography.

Tell us about your journey to being diagnosed with FA.

I was diagnosed with Friedreich’s Ataxia when I was 15 years old. In the lead up to being diagnosed, I remember feeling quite tired, and it being a painful tiredness, with pain in my joints and muscles. I remember turning my ankle and being unsteady on my feet sometimes. At first these were dismissed as growing pains, but eventually the GP referred me to neurology at the John Radcliffe Hospital in Oxford. This was in the days before the genetic mutation causing FA had been identified (by a project sponsored by Ataxia UK), so I had two days of painful tests involving direct electrical stimulation of nerves before my parents were informed that my diagnosis was FA. Similarly, it was in the days before the internet so my parents had to look up FA in a textbook or similar and discovered the bleak description. It was very difficult for me, for my parents and my siblings. I was in denial when I was diagnosed, and set my focus on achieving all the things I thought I should achieve: going to university, getting a job, earning my own money, learning to drive etc. In 2011 I began feeling tired with everything I was doing: commuting, working full time and bringing up my two young children with my wife, and turned my focus onto giving back to Ataxia UK, my other volunteering roles and my writing. It was only then I could see what a treadmill I was on, and appreciate how truly fulfilling volunteering is.

What is something about living with FA that you feel is underappreciated and is important for our researchers and others to know?

I’ve learnt that a diagnosis such as FA doesn’t only affect the individual with ataxia themselves, but also their parents and siblings and other family members too. They also need help to process the diagnosis and the associated thoughts and emotions. It’s not right to give parents a difficult diagnosis and expect them to pass it on to their children without any support. I also hadn’t appreciated how important pushing yourself physically is, and I wish I had learned sooner that keeping active and doing stuff is so important. There is an important physical side of not being active that is very easy to overlook, and it comes back to how disability is generally perceived by society – that disabled people can’t do fitness and health and that fitness is seen as being a possession of the able bodied. It is about empowering disabled people. I have worked hard with Ataxia UK to recognise and develop volunteers with ataxia throughout the organisation.

What, in your opinion, is the best thing the FA Alliance at Oxford can do to help people with FA?

This is a difficult question to answer! It is brilliant that we have researchers and medical professionals striving to find a cure and develop treatments and therapies to help us. For me, the biggest thing that I would change if I could is the lack of counselling offered to people when they’re diagnosed. Receiving a diagnosis such as FA, and the implications you’re told it will have on your life can take a long time to come back from, and it did set me back years. There is a lack of understanding of disability in general, particularly from many medical professionals and we need to challenge the way disability is perceived by people. Finding a cure is good, but it is not enough. Greater focus needs to be on keeping disabled people healthy. I also advocate for a move away from the term “rare disease” in favour of “rare condition” to help remove some of the negative connotations of having a disease or disability. We should use better terminology and aim for an inclusive approach to help people live with their disability; tell people about exercise, which gyms they can go to, speech therapy, physiotherapy, what mobility aids can help restore independence, what living aids are available to them to have in their homes, providing respite care and financial support for carers. We should take a more positive approach to disabled people and welcome disability in our lives.

If you have any queries about the FA Alliance at Oxford, suggestions for content for this bulletin, or wish to unsubscribe from receiving the bulletin, please contact Geoff.