Gene therapy-based strategies for spinal muscular atrophy-an Asia-Pacific perspective.

Onasemnogene abeparvovec has been life-changing for children with spinal muscular atrophy (SMA), signifying the potential and progress occurring in gene- and cell-based therapies for rare genetic diseases. Hence, it is important that clinicians gain knowledge and understanding in gene therapy-based treatment strategies for SMA. In this review, we describe the development and translation of onasemnogene abeparvovec from clinical trials to healthcare practice and share knowledge on the facilitators and barriers to implementation. Rapid and accurate SMA diagnosis, awareness, and education to safely deliver gene therapy to eligible patients and access to expertise in multidisciplinary management for neuromuscular disorders are crucial for health system readiness. Early engagement and intersectoral collaboration are required to surmount complex logistical processes and develop policy, governance, and accountability. The collection and utilisation of real-world evidence are also an important part of clinical stewardship, informing ongoing improvements to care delivery and access. Additionally, a research-enabled clinical ecosystem can expand scientific knowledge and discovery to optimise future therapies and magnify health impacts. Important ethical, equity, economic, and sustainability issues are evident, for which we must connect globally.

Co-designing interventions to 'live well': experiences and perceptions of the Genetic, Undiagnosed and Rare Disease (GUaRD) community.

The Genetic, Undiagnosed and Rare Disease community faces a range of hurdles to live their 'best life' including physical, social and psychological barriers. They are also resilient and experiential experts with insight into what works and what could work for them. In this study, we aimed to identify and prioritise practical interventions the Genetic, Undiagnosed and Rare Disease community report could help them to 'live well'. Using a three-stage approach, we first analysed data from a year-long Genetic, Undiagnosed and Rare Disease journal study to record all the practical interventions reported, either trialled or proposed. Second, after grouping the interventions (n = 19) into four themes (support for individuals with GUaRD; support for carers of people with GUaRD; education/employment; transition), we presented the interventions to members of the GUaRD community (people with GUaRD, their carers and peer support group members) across three focus groups (n = 13). Focus group transcripts were analysed for refinements to the interventions, barriers and/or enablers to enacting them and for any additional interventions suggested. From this analysis, the interventions were grouped to identify specific actionable activities (n = 8). Finally, these eight interventions were discussed in a workshop with the GUaRD Community Advisory Group and prioritised using the APEASE framework. Prioritised interventions targeted a range of stakeholders and included creating a lived experience video library, supporting peer support groups with grant applications, and educating clinicians about referring to peer support groups. Further research is now required to test these findings before trialling and evaluating an intervention to measure the impact on the GUaRD community.

The Australian Reproductive Genetic Carrier Screening Project (Mackenzie's Mission): Design and Implementation.

Reproductive genetic carrier screening (RGCS) provides people with information about their chance of having children with autosomal recessive or X-linked genetic conditions, enabling informed reproductive decision-making. RGCS is recommended to be offered to all couples during preconception or in early pregnancy. However, cost and a lack of awareness may prevent access. To address this, the Australian Government funded Mackenzie's Mission­the Australian Reproductive Genetic Carrier Screening Project. Mackenzie's Mission aims to assess the acceptability and feasibility of an easily accessible RGCS program, provided free of charge to the participant. In study Phase 1, implementation needs were mapped, and key study elements were developed. In Phase 2, RGCS is being offered by healthcare providers educated by the study team. Reproductive couples who provide consent are screened for over 1200 genes associated with >750 serious, childhood-onset genetic conditions. Those with an increased chance result are provided comprehensive genetic counseling support. Reproductive couples, recruiting healthcare providers, and study team members are also invited to complete surveys and/or interviews. In Phase 3, a mixed-methods analysis will be undertaken to assess the program outcomes, psychosocial implications and implementation considerations alongside an ongoing bioethical analysis and a health economic evaluation. Findings will inform the implementation of an ethically robust RGCS program.

Living with a genetic, undiagnosed or rare disease: A longitudinal journalling study through the COVID-19 pandemic.

INTRODUCTION: COVID-19 changed the way we lived with uncertainty from the outset as the pandemic impacted every aspect of our lives from well-being, socializing to accessing healthcare. For people in vulnerable populations, such as those with genetic, undiagnosed and rare disorders, the experience was heightened. AIM: The aim of this study was to identify how the rapidly changing COVID-19 environment impacted the lives of the Genetic, Undiagnosed and Rare Disease community. METHODS: From June 2020 to May 2021, we collected monthly open-ended journals from people living in Australia with genetic, undiagnosed and rare disorders. Data analysis was deductive, using the Resilience Scale for Adults, and inductive using thematic analysis. RESULTS: We recruited 29 people (average of n = 9.7 submissions each month). Responses changed over the year, with initial journals focusing on the importance of developing new structures for day-to-day lives, while later journals started to focus on mental well-being. Throughout the project, participants reported challenges in accessing health and social care that was compounded by fear and concern over being exposed to the virus. Later journals highlight inconsistent messaging for vaccinations for this vulnerable community. DISCUSSION/CONCLUSION: In parallel with the waves of the COVID-19 pandemic, there need to be waves of targeted support for vulnerable communities. The first support wave needs to focus on facilitating the identification of new frameworks to structure day-to-day lives. A later second wave needs to focus on mental well-being and coping with isolation, while consistent communication relating to health and social care throughout was essential. PATIENT/PUBLIC CONTRIBUTION: This study was co-designed, co-led and analysed with a patient support network.