FX Info newsletter May 2020

May 2020 Dr Marcia Braden Carrier screening Clinical trials Research studies Family stories

and more‌...

Tim

Welcome to our first newsletter for 2020 The year got off to a great start with the seminars with Dr Marcia Braden in Melbourne and Sydney.

This newsletter provides a great overview of some of the developments emerging in the Fragile X space.

Marcia arrived on the 1st March and was in Australia for 10 days, speaking at seminars and holding clinic consultations with 14 children and adults. Marcia then went to New Zealand for the FX NZ family conference and seminar. We were so lucky with the timing … this whirlwind tour was finished just ahead of the coronavirus border closing and isolation processes in both countries.

Prof Ted Brown’s overview of the clinical trials in Fragile X syndrome, most of which are being conducted in the US, notes that several of the trials, including the Zynerba trial, are due to report in the middle of this year. There is also progress being made in terms of genetic carrier screening. FXAA has for many years advocated for the wide availability of testing and screening for Fragile X, and it is good to see the progress on this front, in Many thanks to Zynerba Pharmaceuticals for providing a particular through the Mackenzie’s Mission research grant which helped fund two of the seminars and the study. FXAA and a number of our members have production of a couple of short videos, and to Hireup and supported an application currently before the health Australian Catholic University for providing seminar department for public funding of carrier screening of FX, venues in Sydney at no cost.

CF and SMA and we look forward to hearing the results.

The coronavirus COVID-19 has impacted everyone in the community, in many different ways. It has been difficult and challenging being homebound, with children at home, and no access to supports. It has been a bit of a learning curve for many of us getting in touch with friends and families over Zoom – having dinner, drinks or even birthday celebrations online.

Liz, our Family Support counsellor, has been making great use of Zoom to keep in touch with our members, and hosting group discussion sessions. Zoom has proven to be a fantastic way to connect up families in different states, who would not otherwise meet.

While Liz and I put processes in place to work from home if necessary, we found that we were able to remain in the office – socially distanced, of course!

We’ve kept in touch with our Board members via Zoom as well.

I acknowledge and thank the families who have provided input to the ongoing Disability Royal Commission, in particular Narelle Reynolds who appeared at a public hearing on disability and healthcare in February to talk about her sons’ experiences.

Many thanks to everyone who has contributed articles for this newsletter, and supports our small and energetic organisation in so many ways.

Enjoy all our news!

Wendy Bruce Executive Director

Liz with Dr Marcia Braden in our office, March 2020

The week of 18-24th May was a great opportunity to thank the many people in all states and territories who support our community by volunteering their time, skills, connections and energy. By helping spread the word about FX at medical conferences, fundraising, giving expertise of all kinds, serving on our Board, advocating for services and support for people affected by Fragile X, talking to the media, lighting up our world orange on July 22nd, and advocating for change. And more....

Thank you for volunteering. We can’t do it without you!

Image credits: Cover photo of Tim Rodgers taken by Daniel Linnet of LinnetFoto for Fragile X Association of Australia.

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Your Donation Helps Us Support the Fragile X Community Fragile X Association of Australia is a registered charity, funded by donations and fundraising.

We have two staff members. Donations are more important than ever to resource our Helpline and Family Support services, as the impact of the COVID-19 pandemic has restricted event-based fundraising for at least the remainder of this year.

MAKE A TAX-DEDUCTIBLE DONATION BEFORE 30 JUNE Your donation will enable us to continue supporting Fragile X families across Australia and promoting awareness & early diagnosis of FX-associated disorders.

DONATE ONLINE

Through our website www.fragilex.org.au with a one-time or recurring donation

Donate to support our ongoing services and work: * * * * * *

Set up a Facebook fundraiser Fee-free, with funds remitted through Paypal

Helpline: 5 days per week, 9:00-5:00pm Family support counselling Referrals Website and information resources Support groups Workshops and seminars

DONATE OFFLINE

By cheque or phonecall Donations of $2 and over are tax deductible.

What a Difference a Virus Makes Tim’s life has altered significantly since the cover photo was taken towards the end of 2019 but he has adapted well to the changes imposed on him by COVID-19.

As the coronavirus established itself across the community Tim progressively “lost” the various elements of his rather busy daily routine: stood down from both his jobs swimming classes suspended tennis class suspended drama class suspended Merry Makers dance group suspended Sailability suspended group social outings discontinued.

drama restarted with the help of FaceTime.

Merry Makers have got together for a chat on a weekly basis with the help of Zoom and Tim has spoken regularly to his group home co-dwellers on Webex.

Some social activities are being organised. And the iPad has had a thorough workout.

Most of us will have experienced this type of disruption during the lockdown phase of the coronavirus but for people with Fragile X, like Tim, changes of this magnitude will have been a real challenge. It has been really encouraging the way he has handled all that has gone on (or not gone on, as the case may be).

By Doug Rodgers

and he moved home living with his family on a temporary basis rather than stay in his supported living accommodation.

In practice not all has been lost and Tim has been able to adapt with only occasional friction with his brother.

He has kept fit with daily walks and some bike riding.

In April his tennis resumed in modified form and in May

Tim Rodgers and family with Wendy Linnet

Many thanks to Daniel and Wendy Linnet for giving their time to take photos of several families in late 2019 to help us raise awareness of Fragile X through the media and our website. www.linnetfoto.com Page 3

Dr Marcia Braden on Supporting Adults and Children It was a great pleasure to have Fragile X expert and psychologist Dr Marcia Braden PhD in Australia in March.

Marcia was in Melbourne and Sydney for the first time since 2015, and was able to catch up with families she has met before and meet new families.

Podcast!

Marcia gave two evening presentations in Melbourne and two in Sydney: Supporting Children and Young People who have Fragile X syndrome, and Supporting Adults who have Fragile X syndrome.

The seminars were well attended by parents and family members, and by service providers, educators and allied health professionals. Marcia also provided clinic consultations for 14 children and adults.

Many thanks to Dr Jonathan Cohen of Fragile X Alliance who co-presented in Melbourne and Sydney, and Dr Jane Law and Michael Cohen who co-presented in Sydney. The videos and slides from these presentations will be available on the FXAA website in coming weeks.

Zynerba Pharmaceuticals provided FXAA with an educational grant to support two of the workshops and some video recording. This support was instrumental in allowing FXAA to provide these seminars and to film educational videos on Fragile X Pictured: Terry Hurst, Zynerba, Dr Marcia Braden, Dr Jonathon Cohen

Jordan O’Reilly (Hireup), Dr Marcia Braden, Adam Lawrence-Slater (FXAA board)

Cynthia Roberts (FXAA), Damien Jones (Packforce) and Matthew Barnwell

Prof Ted Brown, Matthew Barnwell, Dr Marcia Braden

Many thanks to Jordan, Amanda and the team from Hireup for providing their wonderful team space for the Supporting Adults seminar in Sydney, and to our members who participated in a short discussion panel.

A shoutout to Matthew (Matty) Barnwell and Ross Mackenzie who volunteered on the night, helping with set up and meeting and greet the guests.

Alba Prime recording studio with Glenn Biclar (Melbourne) Shawn and Debbie, Melbourne Dr Jonathan Cohen, Dr Marcia Braden, Michael Cohen at ACU Strathfield venue (Sydney).

Many thanks to ACU for providing the venue at no cost to FXAA.

While here Marcia also recorded several short videos on specific FX topics , including: behaviours, the FX cognitive profile, 10 things to know about the Fragile X learning style, females and FX, and supporting independence.

These videos will be ideal for families, educators and service providers.

Available soon on the FXAA website, facebook and youtube sites.

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Family Support Fragile X Helpline Our Helpline is open 5 days a week 9am—5pm EST for any inquiries about Fragile X Call: 1300 394 636 Email: support@fragilex.org.au

Peer Support

Liz Jewell Family Support Officer liz@fragilex.org.au

The Need for Connection and Self-care Sometimes in life when the unexpected happens it’s hard to turn challenges into opportunities, particularly if you’re already feeling overwhelmed and anxious.

This edition of the newsletter acknowledges a range of responses to unexpected change.

For some, change has presented an opportunity to slow down, regroup and learn new skills, whilst for others the transition to a change in routine, remote learning, lack of personal space and limited support has been difficult.

At times like this the need for selfcare is key an undertaking not always possible whilst caring for others. ‘Me time’ is often last on the agenda and hard to enforce when your internal fuel tank is running on empty.

Talking to others can often help make sense of your own situation, as well as offer an opportunity to share ideas, make connections, build on resources and celebrate progress. Coming to the realisation that someone else’s story is similar to your story can ease feelings of helplessness and exclusion.

Group forums using Zoom With the impact of COVID-19-related isolation, we created group forums for families and individuals to connect across all states by facilitating discussion using via Zoom as a platform.

Some groups have focused on specific topics relating to health and wellbeing, education and social supports whilst other groups have connected through age, gender and diagnosis. We will continue to use this as a platform moving forward.

Discussion groups in Facebook The strength of peer support is also demonstrated through the Facebook discussion groups. Thank you to the moderators who convene these groups and make new and existing members feel welcome and heard.

As a carer, validating your needs whilst giving to others often gets overlooked.

You equally need time to replenish your batteries and receive the love and support you give to others. So, how do you find ways to rejuvenate when you are constantly the “go to” person?

What’s helpful varies from one person to the next and may change from day to day. Through lived experience we each develop our own toolkit as a way of coping.

Over the past couple of months, in response to the coronavirus situation, the NDIA has made a number of changes intended to provide better support to participants and their families.

The NDIS Helpline hours were extended, participants can enrol using a downloaded form from the website, planning meetings are by phone, plans can be put in place for up to 2 years, and automatic plan extensions for 1 year instead of 28 days.

Some flexibility was announced around the use of funding for core supports, and the purchase of assistive technology.

Your toolkit for self-care These are some shared suggestions from families and individuals as to what’s been helpful throughout this time of change: Going for a long walk, Painting, Eating healthy food, Talking to a trusted friend, Seeking professional help, Finding a quiet space, Listening to music, Listening to a podcast, Cooking, Planting seeds.

NDIS updates:

https://www.ndis.gov.au/news

Family Support is available to all people in the Fragile X community and can be accessed and provided in a number of ways: Email: liz@fragilex.org.au Phone: 1300 394 636 Face to face: Zoom, skype or (in Sydney) in person Family Support available: Mondays/Tuesdays/Thursdays, 9am-5pm EST Page 5

Research Matters Prof W Ted Brown MD President Fragile X Association of Australia

Where we stand with drug trials for Fragile X Syndrome While past drug trials in Fragile X Syndrome (FXS) have been generally disappointing in their results, there is real reason to be optimistic that current and future trials may have positive outcomes. Here I will briefly summarize some of the current trials and give a bit about their backgrounds. The current COVID-19 pandemic is obviously delaying the completion of some of these trials. However, progress is still being made.

language learning during an intensive language intervention in very young children with fragile X syndrome.

This trial is using an innovative but exploratory new trial design to develop a different way to examine efficacy of an agent, with substantial support as a drug targeting CNS plasticity in mouse models of FXS. The trial, directed by Dr Elizabeth Berry-Kravis of Rush Medical Center of Chicago, US, is using a double blind placebo-controlled parallel-group Zynerba Pharmaceuticals: CBD gel flexible-dose forced titration design in which 100 Enrollment in a randomized, double-blind, placebosubjects with FXS, age 32 months to 6 years of age controlled, 14-week, phase 2-3 trial, sponsored by are entered into a 12-month blinded treatment phase Zynerba Pharmaceuticals was completed in February during which they are randomized 1:1 to AFQ056 or 2020. It enrolled 210 people aged 3 to 17 years with placebo followed by an 8-month (open label) extension FXS, to evaluate the efficacy and safety of a CBD gel phase in which all participants will be treated with the (ZYN002). CBD is the non-psychoactive component of active drug. The flexible dose design will mimic cannabis (marijuana).The trial’s aims were to practice, take into account differential responsiveness evaluate this gel as a treatment for behavioral and the known inter-child variability in drug levels with symptoms, particularly anxiety. A preliminary AFQ056, and allow use of the maximum tolerated announcement of the results is expected by June dose, which is likely to be most effective.

2020.

The estimated completion date is July 2020.

This CBD trial initially recruited subjects from Sydney, Melbourne, and Brisbane, and then later at some 20 sites in the US. The current trial involved subjects with averagely more severe symptoms than their earlier trial. The trial was based on the company’s earlier positive outcome from a smaller controlled trial conducted on 20 subjects in Australia. Zynerba presented results in December 2018 regarding the first trial in Australia, which had demonstrated that treatment with their CBD skin gel improved core emotional and behavioral symptoms, and social avoidance measures of FXS across multiple measures at month 3 (59% improvement), and that these improvements were sustained through 12 months of open label treatment (77% improvement).

FRAXA Clinical Trials The US based FRAXA organization (FRAXA.org) has given grants to support four ongoing clinical trials.

The first to Canadian researchers, Dr. Artuela Çaku and Dr. Francois LePage, is an open label trial of Metformin, recruiting 20 males and females ages 10-40 who have FXS. The trial was scheduled to be completed by September 2019, although results have not yet been released. I understand that this research group has now linked up with the ongoing controlled study of Metformin by Dr Hagerman, see below.

Metformin is the most commonly prescribed drug for type 2 diabetes, to control high blood sugar.

Metformin has emerged as a candidate drug for the In May 2019, the US FDA granted Fast Track targeted treatment of FXS based on animal studies Designation for the company’s CBD gel for treatment showing rescue of multiple phenotypes in the FXS of behavioural symptoms associated with FXS. model (Gantois 2017,2019). In these animal models, This designation is designed to facilitate the Metformin normalizes several aspects of neuron-todevelopment of drugs intended to fill unmet medical neuron communication. Metformin may contribute to needs, and can lead to expedited review by FDA in normalizing signaling pathways in FXS in the central order to speed up getting new important drugs to the nervous system, which include activities of mTOR and patient.

PI3K, both of which have shown to be pathogenically overactive in FXS. In addition, Metformin inhibits phosphodiesterase, which would lead to correction of Novartis: AFQ056 (Mavoglurant) cAMP levels, and MMP9 production, which are also There is an ongoing National Institutes of Healthelevated in FXS. Looking at the potential signaling sponsored trial in 13 sites in the US of the Novartis pathways, Metformin appears to be a good candidate drug, AFQ056 (Mavoglurant), which did not show for targeting several of the intracellular functions in significant improvement in the earlier trials, but which neurons disrupted in FXS and, therefore, has may have been due to testing older-aged subjects and potential to rescue several types of symptoms in for short periods of time. individuals with FXS. While a growing number of families are trying Metformin and reporting some The overall goals of the current trial are to provide a positive results, Metformin is only now being definitive test of the mGluR theory of FXS by systematically trialed in subjects with FXS. determining whether AFQ056, an mGluR5 negative modulator, can enhance neural plasticity in the form of Page 6

The second FRAXA-funded clinical trial of Metformin is to Dr Sean McBride of Rowen University, PA, US to conduct a parallel group design, randomized double -blind controlled trial of Metformin treatment in 40 patients with fragile x syndrome, to evaluate safety and effects on cognition, anxiety, attention and biomarkers. The estimated date of completion is October 2021. This double-blind trial will examine if there are improvements in cognition, sleep, attention and anxiety, as well as examining the effects on markers in blood obtained by a standard blood draw.

The third FRAXA funded clinical trial is of an investigational new drug, and is also led by Dr Berry-Kravis. This trial will treat 30 adult males with Fragile X syndrome with a new enzyme phosphodiesterase 4 (PDE4) allosteric inhibitor designated as BPN14770. The study is planned to be completed by August 2020.

This study is potentially a major advance in clinical FXS research for a number of reasons. First, the enzyme, PDE4, breaks down the signaling molecule cyclic AMP, has been singled out as a promising treatment target for a long time. Many researchers have shown that PDE4 inhibitors can fix Fragile Xrelated problems in animal models. Most recently, FRAXA funded researchers in collaboration with Tetra Discovery Partners, a small biotech company based in Michigan, showed that this new compound had powerful rescue effects in Fragile X mice, which persisted long after the drug was discontinued (Gurney 2017). Tetra has developed an PDE4D allosteric inhibitor which is highly selective, non-toxic, and easy to take. While Tetra is primarily developing this drug for Alzheimer’s, they agreed to branch out into Fragile X. Further, the FDA has granted Orphan Drug Designation to BPN14770 for treatment of Fragile X syndrome, which will speed its availability, should the trial prove successful. One interesting aspect of this study involves a crossover design, with every participant taking active drug for half of the trial period. This will allow the investigators to look for “carry-over effects” in the Fragile X patients that were observed in the Fragile X mice. Trial subjects will also receive a full therapeutic dose of the drug, so clinically meaningful responses are possible.

The fourth FRAXA-funded trial is to Dr Craig Erickson at Cincinnati Children’s Hospital, OH, US. He is conducting a double-blind, placebo-controlled clinical trial of AZD7325 in 15 adults with FXS. The study is expected to be completed by October 2020.

The compound is an investigational new drug from AstraZeneca which selectively boosts GABA(A) receptors. Many studies have shown that the brain’s GABA system is impaired in FXS, and a number of medications that target GABA have shown promise for Fragile X. This initial trial will also use a number of innovative biomarkers which it is hoped will be useful outcome measures for future trials.

Ovid Therapeutics The US biotech start-up company Ovid Therapeutics sponsored a clinical trial of OV101 at 8 centers, which was completed in March, 2020. The company announced positive results in April, 2020. This trial was a double-blind, but non-placebo controlled trial, that evaluated three different doses of OV101 in 15 FXS males, aged 13 to 22. The drug was found to be safe and tolerated. There was significant behavioral improvement reported for the two lowest doses only, which supports their continued development of the drug. OV101 (also known as gaboxadol and THIP) is a δ-selective direct-acting GABA(A) receptor agonist.

There are many types of GABA receptors in the brain, which help regulate neuronal activity, but tonic inhibition is specifically a function of the δ-subunit containing GABA(A) receptors, and has been found to be deficient in fragile X animal studies. In FXS, tonic inhibition is found to be diminished. In animal model studies, OV101 improved symptoms, such as motor function, sleep and aspects of behavior and cognition.

Dr Randi Hagerman is also conducting a centre-funded Metformin study at the UC Davis MIND Institute for 60 FXS patients aged 6 to 25 years inclusive. The trial is about half-way through, has been joined by a Canadian team, and is expected to be completed by May 2021. It is a randomized, double-blind, placebo-controlled trial. Through this trial, Dr Hagerman hopes to further assess Metformin's safety and benefits in the areas of language and cognition, eating and weight loss, and overall behaviour. Each participant is tested for a period of 4 months, including 3 visits to the UC Davis MIND Institute. At each visit, the researchers assess behavioral, cognitive, language development, and any side effects. She previously published positive results for 7 FXS cases, ages 4-60, given metformin in an open label format (Dy 2017). More recently, results of treating 9 young subjects between ages 2 to 7 in an open label format were published (Biag 2019) with a favourable behavioral outcome seen in most.

Finally, Drs Erickson and Berry-Kravis are conducting an internally funded trial of Acamprosate.

This is an approved medication for the maintenance of abstinence from alcohol dependence. It is a GABA agonist and NMDA glutamate receptor antagonist that modulates and decreases neuronal hyperexcitability in preclinical animal studies. An initial open label trial showed behavioral improvements in 75% of 16 FXS subjects (Erickson 2013). This controlled trial aims to analyze the effect of treatment with Acamprosate in 48 Fragile X subjects over a 10 week period in the behavioral problems seen in patients with FXS. The trial recruitment is now closed, and the results are expected to be completed by June 2020.

Prof W Ted Brown, May 2020

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The Disability Royal Commission was established in April 2019 in response to community concern about widespread reports of violence against, and the neglect, abuse and exploitation of, people with disability. https://disability.royalcommission.gov.au/ Over a 3 year period, the Disability Royal Commission will investigate:  preventing and better protecting people with disability from experiencing violence, abuse, neglect and exploitation  achieving best practice in reporting, investigating and responding to violence, abuse, neglect and exploitation of people with disability  promoting a more inclusive society that supports people with disability to be independent and live free from violence, abuse, neglect and exploitation.

Public Hearings

The Commission has held a number of public hearings on specific topics including Education and Learning (Townsville), group homes and other homes and living for people with disability (Melbourne), Education (Brisbane), and Healthcare.

Healthcare services and disability hearing Two members of FXAA made submissions to the Royal Commission for the Healthcare public hearing.

Robyn Iredale made a submission based on the experiences in healthcare settings of her son Marty Campbell, and her brother, Stuart Iredale. The film Stuart X, based on Stuart’s life story and experiences in institutional and health settings and publicly released in December 2019, was included as part of the submission.

Issues Papers

The Royal Commission is publishing a series of Issues Papers to obtain feedback from the community on a range of topics related to disability.

Public responses to Issues papers will be included in the analysis of the Royal Commission, can inform public hearings and the Commission’s recommendations to government.

Employment Issues Paper The Royal Commission is calling for feedback from the community on the experiences of people with disability in looking for, finding and keeping a job.

It is interested in issues relating to job support, career progression, opportunities for training, mentoring, Narelle Reynolds, a Wiradjuri woman from NSW and coaching, professional development and promotion, and former nurse is the fulltime carer of her 2 adult sons transitions from school to work, from one job to another Justin and Luke. Narelle appeared before the Royal and into retirement. The Royal Commission is also Commission and spoke about the “double whammy” of interested to know whether the current range of being Aboriginal with a disability. Her son Luke has also employment programs and supports for people with been diagnosed with thyroid cancer. Narelle has found disability are easy to access, how well they assist people doctors dismissive and lacking insights into the specific to find and keep a job and whether or not the jobs provide and Fragile X-related care needs of her son, resulting in an adequate income. It wants to know how large and poor outcomes for Luke and the family. In order to access small employers can be assisted to help people with better medical and culturally appropriate services, Narelle disability to find and keep a job. moved the family from Dubbo to Coffs harbour, but has struggled to find affordable housing. While Luke and Employment Issues and Fragile X Justin receive NDIS funding, Narelle has not found culturally appropriate services for them. (1) FXAA member Robyn Iredale, will coordinate a submission from Fragile X Association of Australia on this topic.

Narelle said that she had appeared before the Royal Commission in order to highlight the inequities in the health system for people with disability. She called for hospitals to have trained disability workers and better access to culturally-appropriate health services for Aboriginal people.

Narelle’s testimony was covered in the media on ABC and commercial television news, and in an article in The Guardian online newspaper in February 2020.

Feedback from as many people as possible within the FX community across Australia will be important to ensure the submission covers a wide range of experiences in job seeking in the cities, regions, and rural communities; experiences of men and women, and people from varies ethnicities and cultural backgrounds.

A short Fragile X Employment Issues survey will be linked to the FXAA website and our social media in June 2020 to collect feedback from the FX community on employment issues which have been experienced.

If you prefer to complete the survey in writing, please contact Wendy or Liz and we can send you a printed survey.

The closing date for responses to the issues paper is mid August 2020.

Narelle and her family (from SBS website)

(1) From The Guardian, 24 February 2020 Page 8

Family Story: Sophia James

Sophia and James

Sophia and James Congratulations to Sophia James (formerly Sophia Wackerman) for her success in reaching the Top 10 in American Idol 2020 earlier this month.

Sophia has an amazing voice!

and Leonie passed away several years ago but are well remembered in Australia.

Many Australians have been following Sophia’s success on social media, and applauding from afar - as the rules precluded anyone outside the US from voting!

About Sophia Sophia is the daughter of well-known drummer Chad Wackerman. Sophia’s mother Naomi Star was an Australian professional singer and was President of Fragile X Association of Australia from late 2000 until 2004, before relocating with the family to California and becoming very involved in the FX California group.

A name change Katie Perry, who is one of the American Idol judges, was encouraging Sophia to change her stage name to “Star”, as a tribute to her mother, but Sophia decided instead to change her stage name to Sophia James, in honour of her wonderful brother James Wackerman who has Fragile X syndrome.

While filming an American Idol final in Hawaii, Sophia introduced James to an audience of 8 million viewers! and talked about James having Fragile X.

Youtube has some fabulous clips of Sophia’s performances and introducing James, and of Sohpia’s Sophia’s grandmother Leonie Star, also Sydney-based, father Chad talking about the musical talent in their was President of FXAA for some time. Sadly both Naomi family.

My Health Matters folder for healthcare Free resources Order online or download www.cid.org.au

The My Health Matters easy read folder was created to improve communication between people with an intellectual disability and their healthcare providers.

It’s ideal for storing personal information about a person’s medical and health information, how the person prefers to communicate, their weekly routines, family and emergency contacts.

My Health Matters has sections to assist in identifying pain or health problems, and has a feelings and behaviour thermometer to communicate concerns.

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CID has developed a range of free and easy read health resources.

Viruses and staying healthy is a guide for people with intellectual disability explaining how to avoid getting sick from a virus and what to do if they get sick.

Reproductive Genetic Carrier Screening Updates

www.mackenziesmission.org.au

Mackenzie’s Mission is a 3-year commonwealth government funded research study investigating how to best offer reproductive genetic carrier screening to Australian couples. The program was announced in the May 2018 federal budget

by Health Minister Greg Hunt as part and commenced recruiting participants in March 2020. Couples who are planning or in early pregnancy are recruited through selected healthcare providers in targeted regions across Australia.

Mackenzie’s Mission will screen 10,000 couples across Australia for approximately 1300 genes associated with more than 700 severe genetic conditions, including spinal muscular atrophy, cystic fibrosis and Fragile X syndrome. Screening will identify couples with an increased chance of having a child with a severe genetic condition. Education and support will enable couples to make choices about screening and reproductive options in accordance with their own values.

The study aims to determine the evidence for making free reproductive genetic carrier screening available to all couples in Australia who wish to have it.

Fragile X Association of Australia, together with Spinal Muscular Atrophy Australia and Cystic Fibrosis CommunityCare are involved in a the Mackenzie’s Mission Reference Group to provide support group and consumer feedback on the education content, language and consumer focussed presentation in the project.

Reproductive Carrier Screening — What GPs Need to Know The Healthed Annual Women’s & Children’s Health seminars for general practitioners are held in the 5 largest capital cities, and FXAA has provided an information stall at these events for the past 5 years.

This has provided an excellent opportunity to profile Fragile X disorders and testing and screening.

We were at the Healthed seminar in Sydney in February where Prof Graeme Suthers presented on Reproductive Carrier Screening: What GP’s Need to Know, with a focus on screening for key single-gene disorders including CF, SMA and Fragile X. As large events such as these are now restricted, a video of Prof Suthers’ carrier screening presentation will be shown at Healthed’s online seminars for the remainder of 2020, and it is part of a new online learning platform for nurses. Both provide key platforms to inform on reproductive carrier screening.

Spinal Muscular Atrophy Australia has developed a carrier screening website and brochures to profile carrier screening for SMA, cystic fibrosis and Fragile X. These will be disseminated at a range of health professional conferences.

FXAA is keen to keep reproductive carrier screening for Fragile X on the radar of the thousands of GPs who will attend Healthed online events in 2020. With the permission of the RACGP we’ve arranged for a softcopy version of an Australian Journal of General Practice article to be provided to all online Healthed conference delegates:

Healthed conference Sydney, February 2020 Prof Ted Brown and Wendy Bruce (FXAA) with A/Prof Kristine Barlow-Stewart (Mackenzie’s Mission)

Preconception and antenatal carrier screening for genetic conditions: The critical role of general practitioners, by Prof Martin Delatycki et al. AJGP, vol 48, Issue 3, March 2019.

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Reproductive Genetic Carrier Screening Update Proposal for public funding of genetic carrier screening for Fragile X, cystic fibrosis and spinal muscular trophy An application has been made to the Commonwealth Department of Health for public funding (via Medicare) of reproductive carrier screening for Fragile X syndrome, cystic fibrosis and spinal muscular atrophy.

The application is for public funding for:

Public comment invited by 4 June 2020 The government’s Medical Services Advisory Council (MSAC) is now calling for public feedback on the submission, by way of a survey.

The survey is brief, takes around 15 minutes to complete, and is downloadable from the Medical Services Advisory Committee application 1573 page:

“Carrier screening of asymptomatic couples with no |family history of cystic fibrosis, spinal muscular atrophy or fragile X syndrome (who are planning or in the early stages of pregnancy), for detection of heterozygous mutations in the cystic fibrosis transmembrane conductance regulator, survival motor neuron 1 and fragile X mental retardation 1 genes.

www.msac.gov.au/internet/msac/publishing.nsf/ Content/1573-public FXAA and Fragile X Alliance have submitted responses to the survey.

This will identify couples at approximately 25% risk of Responses from individual members of the public having a child with cystic fibrosis, spinal muscular are also being called for. atrophy or fragile X syndrome, in order to provide them with reproductive options that may prevent the birth of an affected child.”

The application, made by the Royal College of Pathologists of Australia (RCPA) in 2018, included letters of support from Fragile X Association of Australia, Spinal Muscular Atrophy Australia and Cystic Fibrosis Community Care VIC/NSW.

FXAA members are encouraged to consider providing comments on this proposal via survey by 4th June, in advance of a meeting in July at which MSAC will make a final decision on public funding of this screening for FX, CF, and SMA.

The biennial National Fragile X Foundation conference in the US is a highlight on the FX calendar. It brings together hundreds of families and key clinicians and researchers from across the US as well as many international visitors. This year, due to the COVID-19 pandemic, the NFXF team is bringing a virtual conference to the global FX community.

This virtual 3-stage conference presents a unique opportunity for anyone in the FX world to hear from families and experts on Fragile X-associated disorders.

May 29-30 2020

Fragile X Syndrome across the Lifespan Focus on living with and caring for individuals with Fragile X syndrome

June 27 2020

Premutation Carrier Issues Caring for yourself, FXTAS, FXPOI

July 22 2020

Fragile X Research Roundup Live sessions with Q&A from the top researchers

One-time registration Sessions: Tickets on sale:

Covers all dates and access to presentation slides and articles Live and on-demand until the end of 2020 https://fragilex.org/get-involved/international-fragilex-conference/ Page 11

Family Story: A FXTAS Journey Helen McAlley has written a short book to recount her husband Peter’s diagnosis of FXTAS, and her experience in coming to terms with his illness.

Our Family Support Counsellor, Liz Jewell, asked Helen what supports helped sustain her through the difficult times of Peter’s illness.

Helen said: “My Christian faith and the Church community as well as family and friends have been a great source of support and remain so. Whilst Peter was in the nursing home I would visit each day for a few hours. I also found it was important to maintain the routines of life, socializing and exercising whenever possible.“ This is an extract of Helen’s book which will be published in the coming months:

Peter with his granddaughter Miriam

“Peter and I lived in Cleve in remote South Australia from Professor Storey sent me out of the room while he gave 2010 until 2015. We were ordained there as Anglican Peter some tests to assess his intellectual ability. clergy.

He explained that some partners found these tests difficult. He confirmed that Peter (who had spent most of I ...remember how Peter took a funeral at Cleve and how his working life as a university lecturer) did have some he said the same prayer twice....Someone near me deficits, but also said that the progress of the condition commented at that time on this repetition and I felt rather could be quite slow and he knew of people who managed awkward and embarrassed about it. Looking back, I can for 'decades' with the condition reasonably stable. I clung see that his short-term memory was affected by his on to this information hoping against hope that this would condition which we then had no name for... be the case for Peter....

Then in about 2012, we were on our way back to When faced with a diagnosis like this, it is difficult to take Melbourne and stayed overnight with our daughter it all in. I remembered how we had received a diagnosis Bronwyn, her husband Sean and their daughter Miriam in for Vaughan our son when he was 20 years old. The Mildura. lung problems he had had for years were finally revealed

to be symptoms of cystic fibrosis. When given this label, I remember how it was on my mind all the time for the next week or so. I would lie awake thinking about it at night. On the train, I would be doing the same thing, going over it in my mind trying to make sense of it. I clung to the thought that his symptoms would not be too Bronwyn went on to say that Peter might be a carrier and devastating and that he would be able to have a the symptoms he was experiencing could be the result of reasonably normal life. a condition that can affect the older carriers of the Fragile I desperately hoped that Peter too would be able to keep X gene - Fragile X Tremor Ataxia Syndrome (FAXTAS). living normally. He did not have a noticeable tremor and I thought that this was a good sign and maybe this meant While we were in Melbourne, we had an appointment that the disease was progressing slowly and that we with Professor Elsden Storey who ran some tests on would still have plenty of time together to do the things Peter and confirmed that he was indeed a carrier and we had planned for our later years.“ was suffering from the syndrome.

On this occasion, Bronwyn had some news for us.

Miriam aged six had been having some symptoms and had been diagnosed with Fragile X Syndrome - a genetic condition which can cause a child to be behind in their 'milestones' and have some intellectual disability....

Peer Support: If you or a family member are caring for someone who has FXTAS and would like to talk to someone else who has experienced this, Helen can be contacted by email or phone. Helen is a former Anglican minister and has trained as a counsellor.

Helen McAlley: mcalley1@aussiebroadband.com.au or 0398416886

New FXTAS booklet For more information about FXTAS: www.fragilex.org.au/fxtas/

Men’s Health and the Fragile X Premutation 32-page booklet by Prof Stephanie Sherman and team from Dept of Genetics, Emory School of Medicine, Atlanta, Georgia (US)

If you or a family member have a recent diagnosis of FTXAS and are looking for medical journal articles about FXTAS to pass on to your health practitioners, please contact us on the FX Helpline:

The FXAA website will link to an online version of the booklet as soon as it’s available.

1300 394 636 or support@fragilex.org.au Page 12

Family Story: To Let Go When my youngest child, Peter, was at kindergarten it was recommended by his teacher that he have a paediatric assessment, as his learning ability and motor skills were low for his age. After many tests, including blood tests, they needed to rule out any other problems.

After some time the results showed that he had a genetic learning disability, Fragile X syndrome.

and set off for school too! Peter was settled that day to have a familiar face around him, which made the teacher and Peter’s classmates pleased.

On the first day of school, Peter was a very anxious boy with regard to the new environment and the strangers around him. I could tell he was very insecure; however he settled in quite well sitting down at his table to play, even saying goodbye when it was time for me to leave. (I did remind him that I would be back to pick him up soon.) But by the time I had arrived home the phone was ringing and it was the teacher asking if I could come to collect Peter as he was disrupting the class. It was a good thing that the school was a short distance from home.

This continued on each day of the first week of school.

I had to find a solution for my little boy in order for him to settle into school.

By the end of all this, spending alternate times at school, what a difference! When we arrived at school each morning, Peter would put his bag away, give me a hug and say "Bye Mum", with a smile to follow.

The next week it was time to change tactics and I decided I would not stay for the full day but decrease my time spent at the school each day. I told Peter that I would not be in the classroom to help but that I would come at It was recommended that Peter begin speech and playtime and lunchtime, and he was pleased with this. I occupational therapy once a week. With weekly visits and did as I promised for that week. Peter was so excited to much homework that needed to be done I came up with see me there but he also learnt that it was okay to play an idea to help him a little more. To help with his word with the other children. I would sit and watch him in the pronunciation I used a full-sized photo album and found playground but he would now and again turn around just pictures which were of things which began with each to check whether I was still there. letter of the alphabet. These were placed in their As the weeks continued, things would be different again. categories: a picture of an apple was on the A page, a ball on the B page and cat on the C page. I continued this As he was happy and secure and school was not so until the letter Z. Peter enjoyed this book so much and we scary, l felt it was time for a new strategy. I would tell Peter that I could not come at playtime but only for lunch would practice sounding out the words each day.

By the time the year had finished he had graduated from and with this he was agreeable. I would alternate between play and lunch time, which worked out very well. kinder and his speaking had really improved.

What a shock for me.

With tears in my eyes and a tug to my heart my boy had grown up. This does not mean that there weren’t teething problems but it was much easier from then on, all around. Everybody was happy and we had both learnt to “let go.”

On the second week we tried again, but to no avail. The teacher was at her wits’ end by this time as well as my son and myself. I had asked to have a meeting with the school Principal and teacher to devise a plan. I had suggested perhaps I could spend a day in the classroom Written by Johanne Dajic, with Peter and his fellow pupils to assist in his integration, about her son Peter’s and that perhaps I could also assist the teacher in any transition to primary school. way with the other children. This idea seemed like a good Peter and Johanne, May 2020 one, so the next day mum packed her lunch and a drink

FXTAS Clinics In Australia two neurology clinics Sydney and Melbourne have a focus on patients who are premutation carriers who have developed symptoms of FXTAS, or believe they are at risk of developing FXTAS. Some neurologists in other states and cities also see patients with FXTAS. Contact our FXAA Helpline 1300 394 636 if you are seeking a neurologist with experience in FXTAS.

FXTAS Clinic Caulfield Hospital 260 Kooyong Rd, Caulfield

FXTAS Clinic Movement Disorders Clinic 390 Victoria St Darlinghurst

Fridays 9am-1pm

Last Monday of a month 2:00pm-4:00pm Phone: 02 8382 3115 GP referral to:

GP referral to: Dr David Szmulewicz

Dr David Szmulewicz Page 13

Dr Samuel Bolitho

Australian Fragile X Syndrome Research Update Update on the FreeFX study: Exploring the Impact of Mosaicism Size mosaicism, which is defined as the presence of both a premutation (PM) repeat expansion (55-199 repeats) and a full mutation (FM) repeat expansion (≥ 200 repeats), has been reported to occur in about a third of males and 10% of females with Fragile X syndrome (FXS). However, there is little research that has explored the differences in the clinical characteristics of individuals with size mosaicism compared to individuals with only a FM repeat expansion.

Determining the Economic Costs Associated with Raising and Caring for a Child who has Fragile X syndrome As part of the FreeFX study1, a new tool was developed to determine the economic costs relating to raising and caring for a child with FXS and other rare genetic conditions (Angelman Syndrome, Prader-Willi Syndrome and Chromosome 15 Duplication Syndrome).

Many of the FXS community assisted the team at MCRI by participating in the FreeFX study and completing some brief surveys last year. This data has been invaluable in A study published in the Journal of Neurodevelopmental allowing the team to determine the economic costs of Disorders in December of 2019 compared the intellectual raising and caring for a child with a rare genetic functioning and behaviour characteristics of males and syndrome in Australia. This component of the study was females with FXS with and without size mosaicism. undertaken with Dr Sheena Arora from the Centre for This study used data collected as part of the FreeFX Health Economics Research and Evaluation, University study1 which included many Australian and Chilean of Technology Sydney. The study findings are being families with a child with FXS. prepared and will shed light on both government and family costs, which we hope will be informative for the The paper demonstrated that while females have better clinical care of the individuals with these syndromes. We intellectual functioning, they had a similar severity of would like to thank all of the families and children who autism symptoms and challenging daytime behaviours have been involved in these studies and we look forward compared to males, after accounting for the contribution to sharing the results with you soon! of intellectual functioning. This suggests that the more severe behavioural features that are frequently seen in 1 males with FXS is likely attributed to the greater cognitive The FreeFX study is a research program conducted by the Diagnosis and Development group, led by difficulties. The findings also supported that individuals Associate Professor David Godler at the Murdoch with size mosaicism tend to have less difficulties in the areas of intellectual functioning and behaviour. However, Children’s Research Institute in collaboration with Dr Mithere was still a large amount of variability in the profiles chael Field and Hunter Genetics, and Dr Lorena Santa Maria and the Laboratory of Molecular Cytogenetics in of both males and females with size mosaicism.

Santiago, Chile.

If you have any queries about these studies, please get in touch with Dr Emma Baker, MCRI. emma.baker@mcri.edu.au Dr Emma Baker

Australia Day Honour Congratulations Congratulations to Dr Robyn Iredale PhD AM, former President of Fragile X Association of Australia, on receiving an Australia Day honour in January.

Robyn was appointed Member (AM) in the General Division in the Order of Australia for significant service to people with an intellectual disability, and to education.

Robyn served on the Board of Fragile X Association of Australia from 2003 to 2013, and as President from 2013-2016. 14 of Robyn’s family members are affected

by Fragile X in some way. Robyn has been very active in raising public awareness of Fragile X syndrome, including advocacy and in sharing her family’s story of Fragile X syndrome in a range of media including the Employable Me ABC documentary in 2017, and the short film Stuart X directed by Thibault Upton for FXAA in 2019.

Robyn’s academic work includes senior roles at the ANU Australian Demographic and Social Research Institute, and work and research over many years in migration and ethnic affairs in the Asia Pacific.

Robyn with her son Marty at the launch of her book Growing up with Fragile X syndrome: The Road to Marty Campbell, in 2012.

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What a Difference a Virus Makes The COVID-19 pandemic was a challenging time for many families. It was also an opportunity to be creative, explore new interests and get jobs done.

Page 15

COVID-19: Surveying Impacts on Children with Disability Quite a range of organisations are now seeking feedback from families about their experience during the main period of impact of coronavirus pandemic in Australia. The researchers are looking to determine the key impacts on life for people with disability and their parents and siblings, to inform development of supports in the event of similar times of crisis.

Here we have profiled surveys from three organisations which are known to FXAA and have an interest in developmental disabilities including Fragile X. Links to these surveys can be found on the FXAA website, on our Research page.

Learning in a Time of Crisis COVID-19: National Education Survey Children and Young People with Disability Australia (CYDA) is the national peak body representing children and young people (aged 0-25) with disability.

Responses are invited from: * children/young people with disability (aged 0-25 years) * parents or carers of a child/ young person with disability

Every year CYDA runs a National Education Survey.

This year their survey is different because of the impact of COVID-19 on educational experiences for children and All responses will be confidential, and young people. CYDA will use the information to advocate CYDA does not collect identifying to government about the needs of children and young information. people with disability during this time.

Mary Sayers CEO of CYDA Link: https://www.surveymonkey.com/r/5LQ2M63 invites members of the Fragile X community to and: /www.fragilex.org.au/understanding-fragile-x/ complete this survey about the research/ education experience of students who have Fragile X Open until: Completion time:

30 June 2020 10-15 minutes

The Mental Health and Well-being of Children with Neurodevelopmental Conditions or Rare Genetic Disorders during the COVID-19 Pandemic Survey link:

https://bit.ly/2ZqnKDL

and: www.fragilex.org.au/understanding-fragile-x/research/

Open until: Completion time: The COVID-19 pandemic has impacted people in varying ways, and many people are feeling worried, anxious, fearful and overwhelmed by the current situation. Whilst COVID-19 has impacted everyone, it has been particularly challenging for children with a disability and their parents/caregivers and families due to, for example, significant disruption to routines and other factors associated with social distancing measures.

Parents of children aged 0-18 who have Fragile X syndrome are invited to participate this short online survey about the direct or indirect impact of all aspects of life during the pandemic, including social isolation, not having access to schools and therapy, and the Page 16

30 June 2020 10 minutes

various stressors your family is facing and has been dealing with.

The findings from this survey will be used to inform the development of resources to support families in situations such as the COVID-19 pandemic.

The results will be reported back to those involved and to the Fragile X community through the FXAA newsletter and website.

For more information: Prof Valsa Eapen, Coordinating Investigator 02 9616 4364 Dr Anne Masi, Postdoctoral Research Fellow 02 9385 0621

International Study: How Families with Children with Special Needs are coping with the COVID-19 pandemic More than 35 research organizations worldwide are working together on a research study to understand how parents are coping and what changes their families have needed to make during the COVID-19 crisis.

Autism Spectrum Australia (Aspect) is one of the research partners working on this study.

The findings from this study will help us better understand the needs of families during crises and help us to improve support at times of great disruption. A summary of the study’s findings will be provided through the Fragile X Association of Australia later this year.

Dr Ru Ying Cai from Aspect is leading this project for Australia.

The study is targeting parents of children diagnosed with Fragile X syndrome, Autism, ADHD, Down Syndrome, Intellectual Disability, William Syndrome, or other rare genetic diseases. The children can be of any age.

Ru is a researcher and visual artist. She is curious about finding out how we can improve our mental health and wellbeing through science, research, and art.

Parents are invited to complete an anonymous survey.

Survey link:

https://specialneedscovid.org/

and : www.fragilex.org.au/understanding-fragile-x/research/

Open until: Completion time:

mid June 2020 20-30 minutes

If you have any questions about this study, please contact Ru ryingcai@autismspectrum.org.au

July 22nd is Fragile X Awareness Day

Each year July 22 is Fragile X Awareness Day in Australia, New Zealand and the US. We love to celebrate this day by raising awareness of Fragile X right across the country.

Shoutout to the volunteers and Board members who arrange for the lighting up in different states, and to Kate Stokes (aunt of Harry and Tommy) who creates our posters each year!

Call out for photos for our FX posters: If you have some happy snaps you can share for our posters, please email them to wendy@fragilex,org.au

New! FX Tote Bags These fabulous tote bags are 100% cotton and a great option for shopping!

Cost: $25 each (including postage) Fundraiser for FXAA To order: contact us support@fragilex.org.au

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Fundraising The annual Bridge to Beach paddle race and the Ballarat Dance Awards provide very important fundraising support for us, helping to fund the Family Support counsellor role. Thank you!

Funds raised for FX Family Support role

Our Family Support Counsellor Liz, with FXAA Board member Adam at the race starting point.

The 2020 Bridge to Beach across Sydney Harbour on 23 February was another great race! Around 350 paddlers on all sorts of watercraft took on the 11km paddle. Many thanks to the paddlers and to the Fragile X community who made donations.

Shaw and Partners generously matched the funds raised to $5,000. $12,000 in total was raised to help resource the FX Family Support role.

Photo credits: Diana Shypula, KoshkaMedia

Ballarat Dance Awards 2020

The second annual Ballarat Dance Awards were held in early January. Dancers from all around Victoria signed up to participate in the program. It was a very successful and fun event involving 2 days of dance masterclasses with a third day of competition to determine scholarship and award winners.

VIP guests from the Australian Ballet were involved in the program to inspire the young dancers and to adjudicate, including Xavier Pellin, Megan Connelly and Kirsty Martin (pictured). Proceeds from the competition day were donated to Fragile X Association of Australia, which amounted to $2,300.

Many thanks to Anita Coutts-Delaland who initiated the BDA, and to Jimmy Jones and family, who inspired the BDA connection with Fragile X! Page 18

Revisited

This document can be downloaded as a pdf from www.fragilex.org.au Page 19

Supporting the Fragile X Community Help Line: 1300 394 636

Our Helpline operates 5 days per week 9:00am – 5:00pm EST Family support counselling and referrals Information resources Comprehensive website on Fragile X disorders, including videos Social media, including Facebook discussion groups Workshops and seminars Awareness raising and educational activities

Contact Us for Information or Support

Liz Jewell Family Support Counsellor

Wendy Bruce Executive Director

Monday, Tuesday, Thursday

Monday—Friday

liz@fragilex.org.au 1300 394 636

|wendy@fragilex.org.au 1300 394 636

Help Us Make a Difference for the Fragile X Community Fragile X Association of Australia is a registered charity, funded by donations and fundraising.

Donations of $2.00 and over are tax deductible.

Your donation will help us to provide support to the Fragile X community and to promote knowledge and early diagnosis of Fragile X disorders.

Donate

Fundraise Can you help us fundraise?

Get in touch!

 Donate online: www.fragilex.org.au  Regular donations

 Workplace giving

 One-time donations

 Bequests

Registered office of Fragile X Association of Australia Inc: Suite 204, 20 Dale Street Brookvale NSW 2100 1300 394 636 ABN 18 655 264 477 ARBN 626 478 966 Page 20