Breakthroughs in Early Onset Neuromuscular Disorders

The Challenge

Collectively, rare diseases impact approximately 400 million people globally, with half of these patients being children. Tragically, around 30% of children diagnosed with a rare disease do not survive beyond their fifth birthday, and 95% of these diseases lack an FDA approved treatment. This underscores the critical need for developing life-saving therapies for rare diseases.

Project Overview 

The Rare Disease Genetics and Functional Genomics group, led by A/Prof. Ravenscroft, and the Disease Models and Therapies Team, led by Dr. Rhonda Taylor, are working on developing safe and effective treatments for rare genetic muscle diseases. The project has two primary aims:

• Develop Patient-Centric Models of Muscle Disease: Using patient-derived induced pluripotent stem cells (iPSCs) to create muscle cells that model the diseases. ‍
• Designing and Testing New Treatments for Muscle Disease: Developing targeted treatments to address the root cause of genetic muscle diseases. These treatments include genome engineering (CRISPR/Cas9), antisense oligonucleotides (AONs), and RNA-based therapeutics.

Project Outcomes

Short-term Goals:

• Conduct proof-of-principle studies to identify leading therapeutic candidates.

Long-term Goals:

• Develop better models of muscle disease and test these treatments, aiming to translate them into clinical trials and ultimately improve patient health outcomes.

Measuring Impact

Hearts and Minds measures its impact against six core categories as developed by the Association of Australian Medical Research Institutes. Key highlights include:

Advancing Knowledge

• Awards & Recognition: Members of the Ravenscroft Group have received several awards, including the Safe Harbour Fellowship, a PhD scholarship for ACTA1 therapy research, UWA top-up scholarships, the UWA School of Biomedical Sciences Mid-Career Researcher Award, a spot on Cosmos Magazine's list of 50 remarkable women in Australian STEM, and an EMBL travel fellowship. Most recently, A/Prof. Ravenscroft was named the joint winner in the 2024 Premier's Science Awards in the Mid-Career Scientist of the Year category.
• Collaborations: Partnering with key institutions worldwide and conducting collaborative research involving over 1,300 co-authors from more than 40 countries.‍
• Research Publications: Published 160 research papers, 30 of which have an impact factor above 10.‍
• Knowledge Sharing: Regular presentations at global conferences, and raising awareness through podcasts, media, and events.

Research Capacity Building

• Varied and Balanced Team: The Ravenscroft Group comprises researchers from varied cultural and training backgrounds, including clinical, molecular biology, genetic counselling, and computational fields. The group maintains equal representation of men and women at the postdoctoral, research assistant, and PhD student levels.‍
• Diversity and Inclusion: The Harry Perkins Institute is committed to celebrating diversity and fostering an inclusive environment. The team consists of 312 staff members, with a majority of researchers identifying as women, and are supporting 113 students at various stages of their medical research careers.‍
• Infrastructure: The Harry Perkins facility itself was built to be a collaborative hub for medical researchers, to enhance the quality of medical research in WA and it hosts a biobank of several patient-derived iPSCs available to the global research community.‍
• External Committees: Team members actively participate in advisory boards, committees, and other leadership networks.

Health Impacts

• ‍World-Leading Expertise: A/Prof Ravenscroft is recognised as a global expert in the genetics of severe neurogenetic disorders, ranking as the top expert in Australia for arthrogryposis, congenital myopathy, and nemaline myopathy, and among the top 10 internationally for each. She has led or contributed to the discovery of over 20 novel human disease genes, significantly advancing the field.‍
• Accreditation of Bionano Optical Genome Mapping for FSHD diagnosis: Once this test becomes accredited it will enhance the quality and availability of genetic testing for FSHD, one of the most common genetic muscle diseases.‍
• Clinical Impact: A/Prof Ravenscroft's research provides immediate clinical translation, offering crucial answers to families affected by devastating early-onset genetic diseases. Her discoveries have enabled prenatal and preimplantation genetic diagnosis, helping couples avoid having further affected children, and the identified genes are now included in reproductive carrier screening programs worldwide, including Mackenzie’s Mission. Her work is pivotal in understanding disease mechanisms, modelling diseases, and developing therapies.

“Receiving a definitive result from the Perkins Institute was the most euphoric and relieving moment in our lives. We knew for sure that the rest of our family, who were carriers, would be OK. It also gave us closure. The most life changing outcome of having a result has been that it has enabled us to have another child through IVF and prenatal genetic testing. Our daughter is now almost 18 months old and not a day goes by when I don’t think what a miracle it is that she is here.”

– Mother of five children, two died as infants, Melbourne‍

Economic Impacts

• ‍Cost Savings: The project aims to reduce healthcare costs by improving the efficiency of genetic testing and facilitating clinical trials in Australia.

Social Impacts

• Community Engagement: Engaging with the community through events and media to improve health literacy.‍
• Gene Discovery and Diagnostics: Enhancing access to genetic testing and diagnosis, enabling tailored clinical management and appropriate service access.

Informing Decisions

• ‍Guidelines & Policies: Contributed to international guidelines and A/Prof Ravenscroft has provided expertise in governmental enquiries and holds leadership roles that shape research and decision-making.

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The project is a significant step towards developing effective treatments for early onset neuromuscular disorders, with the ultimate goal of translating these treatments into clinical trials and improving patient outcomes.

‍Funding support from Hearts and Minds Investments, as nominated by Core Fund Manager, Magellan. This content was last updated in July 2024, for further information visit Harry Perkins.