Newsletter August 2021
Research Updates
September 2021 - Upcoming PWS research update:
On the evening on Wednesday 15 September Prader-Willi Research Foundation Australia will be hosting a free research webinar. Professor Marnie Blewitt will provide a short update on the progress of the National Drug Discovery Centre screen and we are honoured to have Larry Glass, Chief Science Offer at Neuren Pharmaceuticals join as the keynote speaker to present Neuren's research into PWS and Rett syndrome.
Online Research Symposium
In May PWRFA hosted the Activating PWS Genes Research Symposium. The aim of the Symposium was to add value to your donations by providing an opportunity for researchers to share updates and insights from their labs. Our keynote speaker from the University of Connecticut, A/Prof Chamberlain, spoke about her groups research into how ZNF274 stops expression of SNORD116, including work towards activating PWS genes via the targeted removal of ZNF274 binding sites. We were also treated to inspiring talks from Prof Blewitt (targeting SMCHD1 for PWS gene activation) and Prof Hannan (epigenetics and neuroplasticity).
The highlight was listening to 14 brilliant Australian scientists tackle the BIG questions head on. These scientists want to know what's keeping the PWS genes silent - so they can turn them on safety. They are developing cell and animal models so they can work out what happens when PWS genes are activated at different ages and stages of development. They were excited to talk expert-to-expert, and keen to learn from each other and work together in the future.
The highlight was listening to 14 brilliant Australian scientists tackle the BIG questions head on. These scientists want to know what's keeping the PWS genes silent - so they can turn them on safety. They are developing cell and animal models so they can work out what happens when PWS genes are activated at different ages and stages of development. They were excited to talk expert-to-expert, and keen to learn from each other and work together in the future.
"In recent news from the Blewitt lab, we've heard that the symposium played an important role in developing a new PhD project that will investigate interactions between ZNF274 and SMCHD1. This project will provide critical information about how imprinting works in the PWS region - information that can be used when designing gene activation therapies.
Treatments on the horizon
In 2020, the PWS community was excited to hear the top-line results of phase 3 trials for two potential new therapies for hyperphagia; Intranasal carbetocin from Levo Therapeutics and DCCR from Soleno Therapeutics. Both companies continue to work with the FDA to obtain approval for these new drugs. The FDA is the American equivalent of our Therapeutic Goods Administration (TGA), the regulatory body which approves new prescription drugs in Australia.
Levo Therapeutics have filed a New Drug Application (NDA) with the FDA for intranasal Carbetocin (LV-101) for the treatment of hyperphagia and behavioural distress associated with PWS. On July 6th 2021 they were granted a Priority Review for their NDA, and as a result Levo anticipate a decision from the FDA about approval of LV-101 by the end of this year.
The pathway to approval for DCCR is more complex.
As at July 6th 2021, the FDA have requested an additional clinical trial.
However, the FDA have also “strongly encouraged Soleno to submit the available data and clinical study reports for the Company’s Phase 3 trial, DESTINY PWS (C601), and its long-term, open-label extension study (C602) to allow them to assess if these studies may provide adequate evidence of safety and efficacy to support the submission of an NDA.”
What does that mean for people with PWS in Australia?
Levo and Soleno have both indicated a willingness to seek approval for their new drugs from the TGA as soon as they have FDA approval in the USA. PWRFA will continue to work closely with Levo and Soleno to support this process. In addition, PWRFA will be engaging directly with the Australian regulatory authorities to ensure that the Health Technology Assessment (HTA) process and associated risk-benefit analysis incorporates the voices of Australians with PWS. Our goal is to get Australians access to any new therapies as quickly as possible.
PWRFA Grant Round Updates
2020 Grant Announcement
We are thrilled to announce that Professor Partha Das from Monash University has been
awarded the PWRFA research grant from the 2020 Round. The $25,000 award is funded by your generous donations to PWRFA. Prof Das is head of the Gene Regulation Laboratory at the Monash Biomedical Discovery Institute.
The award will be used to grow 3D brain organoids (sometimes called “mini-brains”) from PWS patient-specific induced pluripotent stem cells (iPSC). This PWS brain organoid system will be used to study brain development and function in comparison to neurotypical brain organoids. The knowledge gained in this study may identify molecular targets for therapeutic development, and the brain organoid system has potential use as a drug screening tool.
awarded the PWRFA research grant from the 2020 Round. The $25,000 award is funded by your generous donations to PWRFA. Prof Das is head of the Gene Regulation Laboratory at the Monash Biomedical Discovery Institute.
The award will be used to grow 3D brain organoids (sometimes called “mini-brains”) from PWS patient-specific induced pluripotent stem cells (iPSC). This PWS brain organoid system will be used to study brain development and function in comparison to neurotypical brain organoids. The knowledge gained in this study may identify molecular targets for therapeutic development, and the brain organoid system has potential use as a drug screening tool.
2020 Grant Announcement
The annual 2021 PWRFA grant round is currently underway. This is our third grant round.
It will provide up to $25,000 AUD (GST-free) to fund an Australian research project which will improve outcomes for people with PWS. Expressions of interest closed on Friday 9th July, 2021, and three applicants have been invited to submit a full project proposal for our Scientific Advisory Council to review.
The grant round runs annually and you can find more information on our website or by contacting grants@praderwilli.org.au
Our Scientists in the media:
Congratulations to Professor Marnie Blewitt and colleagues:
"Mothers touch lingers in babies genes" - CLICK HERE FOR MORE
"Mothers touch lingers in babies genes" - CLICK HERE FOR MORE
PWRFA would like to congratulate Prof Marnie Blewitt and her colleagues on the publication of their work in eLife (CLICK HERE FOR ARTICLE). This paper elegantly unpacks the role of maternal SMCHD1 in establishing and maintaining imprinting for a range of genes, including genes in the PWS cluster. Prof Blewitt presented some of this research at the recent Activating PWS Genes Research Symposium.
This exciting research suggests that SMCHD1 does much of its job early in development (establishing imprinting), but after that it's only needed by a small number of genes to maintain imprinting, including genes at the MAGEL2 end of the PWS cluster. This is an important finding as it suggests that inhibiting SMCHD1 after birth may be relatively safe and should only affect this smaller subset of genes.
Congratulations to Dr Lauren Rice & Professor Stewart Einfeld
(members of the PWRFA Scientific Advisory Committee)
Along with more than a dozen international PWS experts, they contributed to an important paper titled "Behavioral features in Prader-Willi syndrome (PWS): consensus paper from the International PWS Clinical Trial Consortium".
(members of the PWRFA Scientific Advisory Committee)
Along with more than a dozen international PWS experts, they contributed to an important paper titled "Behavioral features in Prader-Willi syndrome (PWS): consensus paper from the International PWS Clinical Trial Consortium".
This paper is discussed in the following article (CLICK HERE) from The Foundation for Prader-Willi Research. The article does a great job of explaining why consensus definitions are important. This consistency is particularly important for defining clinical trial outcomes.
PWRFA are fortunate to have an esteemed Scientific Advisor Committee (SAC) drawn from Australia's most prestigious research institutes and this article highlights the important role of our SAC members in the contribution to PWS research.
Congratulations to Emma Baker and A/Prof David Godler from the Murdoch Children’s Research Institute and their collaborators for their recent paper titled:
"The Cost of Raising Individuals with Fragile X or Chromosome 15 Imprinting Disorders in Australia - PubMed (nih.gov)
"The Cost of Raising Individuals with Fragile X or Chromosome 15 Imprinting Disorders in Australia - PubMed (nih.gov)
Having accurate costings helps us make a case to government for support and services. We can use it to support the value of providing better health care, including the Health Care Model which is in development. It is also useful in the drug approval process when regulatory bodies are assessing the potential economic impact of new treatments and provides support for PWS to be considered for inclusion in newborn screening efforts nationally.
Clinical trials; opportunities for people with PWS
PRESTO Trial; Exercise for Young People with PWS
Prof Shield’s research team at La Trobe University want to find out more about the benefits of exercising at a community gym for people with Prader-Willi Syndrome. They are looking for young people with Prader-Willi syndrome aged 13 years and over to participate in an exercise-based trial.
Victoria has recently started recruitment, along with the initial sites in NSW and QLD.
For further information, please contact:
- Prof Nora Shields on 03 94795852 or N.Shields@latrobe.edu.au
- Alesha Southby on 03 94796310 or Alesha.Southby@latrobe.edu.au
The feasibility of a mindfulness-based intervention for temper outbursts in Prader-Willi syndrome
While COVID has impacted the timelines, Dr’s Lauren Rice’s study “The feasibility of a mindfulness-based intervention for temper outbursts in Prader-Willi syndrome” is progressing well. The purpose of the study is to evaluate the feasibility and acceptability of a mindfulness-based intervention for managing temper outbursts in PWS. We will also be looking at the impact on anxiety. The study is looking for individuals with and without PWS aged 13 to 30 years who have either a mild intellectual disability or typical IQ. This study will be conducted remotely via phone, email and video-conference and is, therefore, open to families both within and outside Australia.
While COVID has impacted the timelines, Dr’s Lauren Rice’s study “The feasibility of a mindfulness-based intervention for temper outbursts in Prader-Willi syndrome” is progressing well. The purpose of the study is to evaluate the feasibility and acceptability of a mindfulness-based intervention for managing temper outbursts in PWS. We will also be looking at the impact on anxiety. The study is looking for individuals with and without PWS aged 13 to 30 years who have either a mild intellectual disability or typical IQ. This study will be conducted remotely via phone, email and video-conference and is, therefore, open to families both within and outside Australia.
If you are interested in participating, please contact the study coordinator - fhs.devpsych@sydney.edu.au
Australia's first purpose-built Biobank
for Chromosome 15 disorders:
for Chromosome 15 disorders:
Australia's first purpose-built Biobank for Chromosome 15 disorders is now recruiting participants. The Biobank will store tissue samples and clinical data for research into rare genetic diseases caused by changes to genes on Chromosome 15, including Prader-Willi Syndrome (PWS) and Angelman Syndrome (AS). Biological samples, such as blood and saliva, will be collected from people with PWS or AS, and linked to detailed clinical and medical history data. This resource will help us to better understand the links between the genetic changes that cause PWS and AS and the challenges faced by these people. A particular focus is on the mental health problems experienced by people with PWS and AS and how these might be treated more effectively.
The Biobank is located at the MCRI and is a collaboration between A/Prof Godler (MCRI) (pictured above left), Prof Amor (RCH), PWRFA and FAST.
For further information, or to enquire about participating in the biobank please visit here or contact Emma Baker: emma.baker@mcri.edu.au (pictured above right).
Other research news
WAKING UP SILENT GENES; Testing proven cancer research on a devastating childhood condition
A/Professor Pilar Blancafort and Dr Charlene Waryah from the Perkins Institute are experts in activating cancer repressor genes using CRISPR-based epigenetic editing. With a $30,000 grant from PWRFA they have purchased PWS cell lines and other reagents enabling them to apply their novel gene activation techniques to PWS. The full press release can be found here
Parliamentary Inquiry into the approval process for new drugs
On Thursday 22 April 2021, PWRFA was honoured to provide evidence at the public hearing for the Parliamentary Inquiry into the approval processes for new drugs and novel medical technologies in Australia. Our submission, prepared by PWRFA Research Director Dr Diane Webster and presented by Elizabeth Patterson, outlined the critical need for the approvals process to include an accurate and detailed assessment of what it's like to live with PWS, both as the patient and as a parent/carer. Including your voices in the Health Technology Assessment process is an essential step which will ensure the unmet needs of those with PWS are appropriately valued in the risk-benefit equations that underpin drug approval and reimbursement.
PWRFA are grateful to Elizabeth Patterson who represented PWRFA at the Inquiry, sharing her lived experience with PWS and advocating for our community.
Path for PWS Update
PATH for PWS is a study to help us better understand serious medical events in PWS over a 4-year period, as well as evaluate how PWS related behaviours change over time. The data from this study is intended to inform the development and clinical trial design of potential new treatments. Although recruitment has closed, individuals enrolled in the study can continue to make a significant contribution by regularly completing and updating their study surveys.
Serious medical event data collected from October 2018 through March 2021 indicates 33.2% of all study participants have experienced at least one event since the start of the study, while 37.7% of those who have had a documented event have had multiple events since enrolment in the study. Common serious medical events reported to date include mental health issues, gastrointestinal problems, broken bones/sprains and seizures.
We’d like to give a big Shout-Out to the 16 Australian families who are actively completing the surveys that make up the PATH for PWS study. Thank you!
Neuren Pharmaceuticals
PWRFA are excited to be working with Neuren Pharmaceuticals Limited to further their research into PWS. Fostering relationships with organisations such as Neuren is a vital component of PWRFA's mission to drive and accelerate the development of potential therapies for PWS. Neuren Pharmaceuticals is a Melbourne-based, ASX-listed (NEU) biotechnology company developing new therapies for debilitating neurodevelopmental disorders that emerge in early childhood and are characterised by impaired connections and signalling between brain cells.
Neuren’s novel patented drug NNZ-2591 potentially has broad utility in the treatment of neurological disorders, including Prader-Willi syndrome. NNZ-2591 has shown compelling results in a pre-clinical mouse model of Prader Willi syndrome, and a phase 2 clinical trial is being planned. Data from the PWS (magel2) mouse model suggests potential impacts on anxiety and obesity, as well as normalizing insulin and IGF-1 levels.
Neuren’s novel patented drug NNZ-2591 potentially has broad utility in the treatment of neurological disorders, including Prader-Willi syndrome. NNZ-2591 has shown compelling results in a pre-clinical mouse model of Prader Willi syndrome, and a phase 2 clinical trial is being planned. Data from the PWS (magel2) mouse model suggests potential impacts on anxiety and obesity, as well as normalizing insulin and IGF-1 levels.
Fundraising update
Move 15km for PWS this May
Exercise is crucial in the management of PWS and the benefits of exercise enable participation for the PWS community in everyday activities. We were delighted to see so many teams and individuals moving at least 15 km during May. This event raised a phenomenal $70,000 which will be used to advance our strategic research program, designed to attract the brightest minds to PWS research.
Announcing our 2021 Giving Day
Wednesday 20 October 2021
Wednesday 20 October 2021
Following the success of the Finding15 Giving Day in 2020, we have locked in Wednesday 20 October as our Giving Day for 2021. MyCause will again support PWRFA in the running of this event. We look forward to sharing more details with you shortly and hope to see as many families and friends as possible signing up, sharing and getting behind the day to help keep the momentum going in our endeavour to make life better for people with PWS through world class medical research.
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