Research & trials
In line with our strategic plan, we remain committed to supporting relevant research into neuromuscular conditions and we continue to create a collaborative environment where research advances that take place both locally and globally will positively influence the lives of those in our community.
As a subcommittee of the Board of Neuromuscular WA, The Community Engagement & Research Advisory Committee (CERAC) provides advice, supplementary information and recommendations in relation to strategic research initiatives, research scholarship candidates and their performances, and liaises with appropriate research services, foundations, education institutes and hospitals where relevant to us.
The CERAC provides leadership and advice on mechanisms to improve monitoring, benchmarking and reporting of scholarship holders’ research funded by our organisation to ensure we continue to allocate funds appropriately.
We aim to maximise the impact of the limited funds available by identifying research areas that will promise to make the greatest scientific advances and have the most profound quality of life outcomes for our families. We will always ensure that our research strategy aligns to initiatives that have demonstrated advances across the globe and we will always endeavour to collaborate across multidisciplinary environments.
To ensure we continue our focus in an applied manner, we have developed a formalised Research Strategy which defines the priorities for our community and demonstrates our commitment to achieving these outcomes for you.
We will always embrace the successes of the last 56 years and work tirelessly to generate opportunities in the future. If you’d like to know more, please get in touch.
Many of our projects are funded through third parties who entrust us to utilise their money to do great things in the research space for those living with neuromuscular conditions in WA.
TEAM Spencer Research Grants and Scholarships
TEAM Spencer was created by Rick and Ruth Steven, in honour of their son Spencer, who was born in March 2006 with SMA and who sadly passed away just seven months later. Since 2012, TEAMSpencer has dedicated itself to raise funds for Neuromuscular WA through various events with funding earmarked for PhD Students, research initiatives and projects that will support individuals and families affected by Spinal Muscular Atrophy.
Neurodegenerative Disorder Center Inc (NDC) Research Funds
In July 2022, the Neurodegenerative Disorder Center Inc (NDC) Board transferred the balance of the NDC funds, approximately $900,000, to Neuromuscular WA as part of their legal obligation during the winding-up process. This generous donation was made with the specific instruction to direct the funds towards research led by Professor Anthony Akkari and his support personnel. In keeping with the legacy of our esteemed founder, Professor Byron Kakulas, and his commitment to advancing research in neuromuscular conditions, these funds will be used with the utmost care and dedication over the next few years to advance research in accordance with his guiding principles.
The Harold & Sylvia Rowell Scholarship and Research Projects Funds
Harold and Sylvia Rowell, long-standing honorary life members deeply committed to advancing research in neuromuscular conditions, made a substantial bequest 2012. This generosity led to the establishment of the Rowell Scholarship Fund, which awarded its first PhD Scholarship in 2014, with subsequent scholarships awarded in 2015 and 2016. Each scholarship, costing an estimated $30,000 - $35,000 per year, supports up to three scholars simultaneously in their pursuit of groundbreaking research. In addition to funding scholarships, these bequest funds are also dedicated to supporting research projects focused on improving clinical outcomes of neuromuscular conditions, furthering the Rowells' legacy in advancing endeavours in this field.
Current Projects
PHYSIOTHERAPY FOR CHILDREN WITH NMCs AT PCH
Funded by: Neuromuscular WA
Physicians/Researchers involved: Nicola Hanlin
Conducted at: Neuromuscular Clinic at Perth Children’s Hospital
Brief overview: She sees newly diagnosed children, assesses them and assists them in preparing for the NDIS process. Once their plans and service providers are chosen, she liaises with community therapists and offers resources and any assistance that they require. There are comprehensive standards of care that have been developed for most neuromuscular conditions, which are forwarded to therapists with resources about the recommended assessments. The North Star Ambulatory Assessment (NSAA) and timed function tests are key clinical assessments that should be done every 6 months during the ambulatory period. They have predictive capabilities for functional motor changes, critical for monitoring clinical progression, guiding proactive care and equipment needs and are often key clinical indicators in drug trials.
Nicola works in both spinal orthopaedic clinics, liaising with community therapists regarding any issues and plans. A few children with neuromuscular conditions underwent surgeries for their scoliosis deformities in 2022 and the benefits of her presence, knowledge of the children and ability to advocate for them were obvious. She also works with Dr Kate Stannage in the neuromuscular orthopaedic clinic and sees current and new children referred to orthopaedics with neuromuscular conditions, which is very beneficial to ensuring our children have a physiotherapist that knows them and is present to relay relevant information.
Nicola attends the neuromuscular clinic on Fridays and is utilised by the neurologists if there are specific queries or issues regarding orthopaedics, mobility, or other concerns. She does a Charcot Marie Tooth clinic with Professor Lamont once a month where a brief assessment is completed and those that are more significantly impacted are offered separate appointments for a lengthier assessment.
In November 2022, Nicola attended the SMA forum in Brisbane providing an opportunity to hear about the new recommendations for therapy and musculoskeletal management. An ever-changing landscape means maintaining consensus on best practice is imperative. She also visited the Royal Children’s Hospital in Melbourne and spent the afternoon in a neuromuscular clinic which allowed her to see how other states work and to foster relationships with experienced neuromuscular clinicians.
Clinical trials commenced at PCH in 2020 and Nicola was fortunate to have attended clinical evaluator training in France prior to that. This enabled her to receive face-to-face training from the best in the world just before COVID changed everything, with further training since. Motor function is the best measurable outcome in these trials, so the role of the physiotherapist is very important.
Outcomes from project: A brief assessment of each child is undertaken which provides insight into the patient’s capacity for normal physical function and informs the type of therapies and supports the patient requires. Those who are more significantly impacted are offered separate appointments where a lengthier assessment is completed.
Duration of project: February 2020 - current
DEVELOPING CLINICAL PREDICTORS OF DISEASE PROGRESSION IN CHILDREN WITH NMCS
Funded by: TEAM Spencer/Neuromuscular WA Scholarship
Physicians/Researchers involved: Dr Adelaide Withers, Professor Graham Hall, Dr Carlos Milla,
Dr Andrew Wilson, Association Professor Jenny Downs
Conducted at: Telethon Kids Institute, Perth Children’s Hospital, Stanford University
Brief overview: The primary purpose is to determine whether alternative methods to sleep studies such as lung function testing; symptom scores; quality of life indicators; or motor function assessment can better predict the onset of respiratory failure so treatment can be initiated earlier. This then delaying the onset of respiratory failure and death. The secondary aim is to use the findings from a longitudinal cohort study to document and describe the natural history of respiratory disease in these conditions, allowing them to construct clinical guidelines for monitoring respiratory function in patients and determine relevant respiratory outcome measures for future clinical trials.
As of 2022, data collection to identify factors predicting hypoventilation was nearly completed for PCH participants, with data collection continuing at collaborative sites in California and Queensland. Exciting times are ahead when data analysis can begin, allowing the team to elucidate the complex factors which contribute to changes in respiratory and sleep health and how to best identify them.
Vital work is underway to determine how best to define hypoventilation in individuals with neuromuscular conditions. Three posters outlining these findings were recently presented at the 2022 Australasian Sleep Association conference, with one awarded the best poster prize in the paediatric session.
Early results examining home sleep studies in 2022 appear promising and were presented at the Australasian Sleep Association conference. We hope these results will significantly impact clinical practice and allow individuals with neuromuscular conditions to avoid trips to the sleep laboratory in future.
In 2022, the team published ‘Factors influencing participation in home, school, and community settings by children and adolescents with neuromuscular disorders: A qualitative descriptive study’ in the journal of Developmental Medicine and Child Neurology, which investigated barriers and enablers to participation and found that personal motivators are critical to understanding how social and physical supports, accessibility and advocacy enable participation.
‘Respiratory health, sleep dysfunction and mental health in children and adolescents with a neuromuscular disorder: a descriptive qualitative study’ will be published in an upcoming edition of the Journal of Sleep Medicine. This study found that a change in mental health can indicate poor respiratory health and that the treatment of respiratory and sleep problems, including non-invasive ventilation, could significantly improve mental health.
Outcomes from project: Sleep studies being conducted at home as an alternative to attending them at the hospital has been welcomed by families due to the convenience and comfort of not travelling or spending a night away from home. The research outcomes from this project have continued to be reviewed throughout, however the goal remains to be to predict the onset of respiratory failure so we can initiate treatment earlier, which can ultimately delay the onset of respiratory failure and death.
Duration of project: July 2019 – current
BIOBANKING SERVICE AT CENTRE FOR MOLECULAR MEDICINE & INNOVATIVE THERAPIES (CMMIT)
Funded by: Neuromuscular WA
Conducted at: Centre for Molecular Medicine & Innovative Therapies
Neuromuscular WA will be contributing to the sustainability of the biobanking service at the Centre for Molecular Medicine and Innovative Therapies (CMMIT) at Murdoch University.
Biobanking refers to the process of collecting, processing, storing, and distributing biological specimens for research purposes. These specimens can include various types of biological materials such as tissues, cells, blood, DNA, and other bodily fluids. Biobanks play a crucial role in biomedical research by providing researchers with access to well-characterised, high-quality samples for studying diseases, identifying biomarkers, developing new therapies, and understanding human biology.
Annually the teams at Murdoch and several others working with patients within the rare disease sector, prepare major grant submissions (e.g. MRFF Frontiers) to establish a pipeline to accelerate bench to bedside translation or to fast-track diagnosis to N of 1 trials (only one patient in the trial as their disease-causing mutation is unique) for amenable/responsive patients. In all these cases, it is essential to have patient cells (or organoids) available to evaluate and validate potential therapies.
Cryo-storage, or cryopreservation, is a method used to preserve cells or tissues at very low temperatures, typically around -196°C using liquid nitrogen. The process involves slowing down or halting all biological activity within the cells, effectively preserving them in a dormant state until they are thawed and revived for future use.
The Neuromuscular WA funds will contribute towards some cryo-storage equipment and liquid nitrogen backups, the costs of consumables for cell collection, propagation and storage, and salaries for lab work and database upkeep of the biobank. Working with Drs May Aung-Htut, Jess Cale and Kelly Martinovich (CMMIT) and Prof Gareth Baynam (Rare Care Team and Perth Children's Hospital), and a cohort of other clinicians, there is a pressing need to be able to source, grow, cryopreserve and study many patient cell lines, some local, others from interstate or overseas and some funds will also be used for shipping/transportation costs for the cell specimens.
It is estimated that costs associated with generating and storing one cell line costs is approximately $1,000. The timing of cell collection is sporadic and following an initial investment of $25,000 for equipment purchase, annual payments will be made to Murdoch to cover the consumable/salary/equipment costs for the previous 12 months.
We are excited that these funds will keep this initiative going for many years.
Duration of project: June 2024 - current
RESPIRATORY PHYSIOTHERAPY FOR CHILDREN WITH NEUROMUSCULAR CONDITIONS AT PCH
Funded by: Neuromuscular WA
Physicians/Researchers involved: Lisa Paterson
Conducted at: Neuromuscular Clinic at Perth Children’s Hospital
Lisa has a strong background in acute respiratory management for children with complex medical conditions and oversees the management of all children at PCH with technology-related needs. During clinic, Lisa reviews children alongside the respiratory medicine consultants. She also liaises with community providers to optimise respiratory health by promoting and exploring ways to remain physically active, especially if the child becomes less mobile.
It is known that children with neuromuscular conditions may present with, or develop, respiratory muscle weakness, which significantly impacts their ability to cough. The muscles required to take deep breaths and cough are not strong enough and fatigue quickly when they are unwell.
If children have a weak cough, they are unable to clear secretions from their lungs and this puts them at increased risk of developing respiratory complications such as pneumonia.
A CoughAssist™ machine is an insufflation/exsufflation device which delivers a large inhalation followed by a rapid expiration, to achieve an effective cough. In the neuromuscular clinic, lung function and cough strength are routinely measured. When deemed necessary, Lisa can trial CoughAssist™ machines with children and their families.
Once children are comfortable and familiar with the machine they usually benefit from using them on a daily basis and even more frequently while they are unwell. Lisa writes support letters to the NDIS to advocate for funding for children to receive their own machine to use at home and Lisa then reviews them during clinic on an ongoing basis to titrate parameters as needed.
Having a respiratory physiotherapist present in the neuromuscular clinic has been of huge benefit to both children and their families, as it helps them to be able to be proactive in optimising the child’s respiratory health and prevent hospital admissions.
Outcomes from project: A specialist respiratory physiotherapy assessment is completed at the PCH neuromuscular outpatients clinic and when required respiratory physiotherapy treatments and home programs focusing on airway clearance and maintaining chest wall mobility are implemented. Scoliosis correction surgery requires complex planning from the multidisciplinary team and having Lisa onboard to assist in the pre-operative physiotherapy respiratory assessment helps to provide a smoother journey for patients and their families.
Duration of project: April 2022 - current
previously FUNDED
How can the experiences of COVID-19 lockdown inform pandemic preparedness for children with rare neurological disorders and their families?
Funded by: Telethon Kids Institute/Perth Children’s Hospital/Neuromuscular WA
Physicians/Researchers involved: Ms Jessica Keeley, Ms Aysha Stroobach, Ms Meg Huston, Dr Adelaide Withers, Dr Andrew Wilson, Dr Jenny Lam, Dr Jenny Downs
Conducted at: Telethon Kids Institute & Perth Children’s Hospital, Teenagers online across Australia
Set out to study the measurement of respiratory health in children and adolescents with a neuromuscular condition, part of this research involved interviews with parents and children to explore the children’s experiences of their health and participation in the community.
It is essential that we learn from the COVID-19 pandemic experiences of children with neuromuscular disorders to be prepared for future pandemic events. The interviews were an opportunity to also ask about their experiences during the pandemic. It aimed to explore the impacts on the mental, physical and social health and well-being of children with neuromuscular conditions and their families.
Children with a neuromuscular condition and their parents were invited to participate in an online interview about their lives during the COVID-19 pandemic in Australia. 17 families participated in this study including nine adolescents with a neuromuscular condition, 16 mothers and four fathers.
Outcomes: Pandemic preparedness lessons can be found in the experiences of children with a neuromuscular condition and their families. For example, the needs of families were highly individual and some families reported how their experience of their child’s complex care needs made them more resilient in a health crisis setting. These perspectives will inform future policies and procedures around preparing for future pandemic events.
Duration of project: 12 months
Limb Girdle Muscular Dystrophy Research at CMMIT
Funded by: The Centre for Molecular Medicine and Innovative Therapeutics/ Neuromuscular WA
Physicians/Researchers involved: Professor Merrilee Needham, Abbie Adams, Bal Hari Poudel
Conducted at: The Centre for Molecular Medicine and Innovative Therapeutics (CMMIT), a joint Murdoch University/Perron Institute research centre
This research will set out to collect biopsy material from patients for cell preparation, propagation and cryogenic storage in the CMMIT biobank storage facility and undertake whole exome sequencing and other studies on some of the LGMD patients.
CMMIT currently has two research projects using the biobanked LGMD cells (fibroblasts).
The first involves whole genomic sequencing (WGS) of a LGMD patient with no confirmed molecular genetic diagnosis. Perhaps unsurprisingly, this resulted in no definitive mutation being identified suggesting the need for further studies. RNA sequencing is the logical next step as this would identify deep intronic mutations that are not detected by WGS.
The second project involved the use of an antisense oligonucleotide (AOs) in an LGMD type 2B patient. AOs have been successfully used to treat Duchenne muscular dystrophy by altering expression of the dystrophin gene through a process called ‘exon skipping’.
In LGMD the idea was to use AOs to target the membrane-bound protein, dysferlin, encoded by the DYSF gene. Mutations in DYSF cause LGMD type 2B and to date, more than 500 pathogenic mutations in DYSF have been reported.
During 2022, 12 biopsies were performed on patients with inherited disorders, including LGMD and familial hypercholesterolemia, thereby expanding the scope and utility of the CMMIT biobank. Biopsies were also taken from malignant hyperthermia patients.
Funds from this grant also contributed to the purchase of a cell incubator, a crucial requirement for CMMIT’s biobanking of patient samples.
Outcomes: Currently there are no drugs available to treat LGMD. Studies showed that AOs leading to the loss of dysferlin exon 32 from the mature DYSF mRNA result in an isoform that retains some dysferlin function. This suggests that AOs can be used as a treatment for some LGMD cases linked to catastrophic dysferlin mutations.
Duration of project: 12 months
Spinal Muscular Atrophy Research
Funded by: TEAM Spencer
Physicians/Researchers involved: Loren Price & Ianthe Pitout
Conducted at: Centre for Comparative Genomics (CCG) Murdoch University
Thanks to the TEAM Spencer funding, Loren completed her thesis “Applications of antisense oligonucleotides (AO) in designing a therapy for spinal muscular atrophy”. This project looked at using antisense oligonucleotides (AOs) targeting exon 7 of the SMA-causing survival motor neuron gene (SMN2).
Following the research developments and investigation undertaken by Loren, the investigation was expanded and continued at CCG and 2016 saw an extension of our support through another scholarship to Ianthe Pitout.
Ianthe continued the investigation of the application of antisense oligomers to modifiers of the SMN2 gene in order to reduce the severity of SMA.
Outcomes from project: By binding AOs to particular motifs of the gene message, it can prevent exon 7 being excluded from the transcript, and therefore produce increased levels of function.
Duration of project: April 2012 – June 2017
Molecular Studies on Antisense Oligo-Induced Exon Skipping
Funded by: Harold & Sylvia Rowell PHD Scholarship
Physicians/Researchers involved: Oliver Dunhui
Conducted at: Murdoch University
Oliver Dunhui completed his thesis describing the application of “exon skipping” strategies for Duchenne muscular dystrophy (DMD) and extending this type of therapy to other genetic diseases. In 2018, Oliver designed and tested antisense oligos to induce Becker muscular dystrophy-like dystrophins that could be used to treat some of the less common DMD mutations.
These oligos were tested in cultured cells and then in in mdx (dystrophic) mice. The aim is to generate a map showing exon skipping strategies to treat DMD mutations between exons 55 and 78, with the various dystrophin validated by data from the mice. The splice switching strategy used in this PhD project to identify dystrophin mutations that could be amenable to exon skipping can also be applied to other neurological or neuromuscular conditions.
Outcomes from project: Oliver participated the 2019 Annual Meeting of Oligonucleotide Therapeutics Society in Munich, Germany. His poster presentation showcasing the DMD project was acknowledged with a poster award. Oliver submitted a manuscript reporting the DMD project to a premier international journal where it is currently being evaluated for publication. The Parkinson’s work is the subject of a provisional patent and will also be submitted for publication.
Duration of project: September 2016 – 2020
Improving Nutrition in WA Children with Neuromuscular Conditions
Funded by: Harold & Sylvia Rowell Research Project Grant
Physicians/Researchers involved: Dietitians Annie Robertson & Melanie van der Wilk
Conducted at: Neuromuscular Clinic at Perth Children’s Hospital
To provide an opportunity to develop and implement a specialised neuromuscular dietetic service as part of the clinic at Perth Children’s Hospital (PCH). Part of this service involves screening growth parameters for all patients who attend the clinic. Patients are offered a one-on-one appointment if they have been newly diagnosed with an NMC, are starting steroids, or are identified as being at nutritional risk (malnutrition or overweight/obese) on their growth screening.
The goal of this project is to improve the nutrition of all children attending the clinic and demonstrate the need for an ongoing specialised nutrition service for WA children with NMCs.
We aim to fill the gaps within the health services needs of the WA community and ensure plans are put in place as part of best practice clinical care to address the holistic needs of children with NMCs.
Outcomes from project: As the project was so successful, well-received by all patients and their families and demonstrated patient need, from July 2021 PCH began offering the dietician services as a fully-funded service within the NMC clinic.
Duration of project: July 2018 – 2021
Spinraza Treatment for Spinal Muscular Atrophy Patients at Perth CHILDREN'S hospital
Funded by: TEAM Spencer
Physicians/Researchers involved: Nurse Jodi Mann and Dr Maina Kava
Conducted at: Perth Children’s Hospital
In June 2018 the drug Nusinersen (Spinraza) for the treatment of Spinal Muscular Atrophy (SMA) was added to the Pharmaceutical Benefits Scheme (PBS) in Australia. Nusinersen is an antisense Oligonucleotide that works by helping the body to produce more survival motor neuron protein which in turn reduces the loss of motor neuron nerve cells and improves muscle strength.
Due to a lack of funding from the government (which would have meant no Spinraza treatment in WA), MDWA invested money from the TEAM Spencer Fund to allow PCH’s Neurology Department to employ nurse Jodi Mann to work alongside Paediatric Neurologist Dr Maina Kava to start administering the medication in June 2018. The team have several SMA patients receiving Nusinersen at PCH and it remains a very successful program.
Outcomes from project: An incredibly successful Nusinersen program has been set up at PCH with all doses being delivered in their Day Treatment Unit and under minimal oral sedation. Over the past 18 months that this medication has been available to SMA patients, the team have successfully delivered approximately 65 lumbar punctures to patients and seen some amazing improvements in the children’s' motor function and abilities, as well as overall general health. This medication has completely changed the natural disease history of SMA patients and the team has also had to adapt to new treatments and clinical practices to keep up the pace.
Duration of project: June 2018 - 2019