Genetic Epilepsy Team Australia - GETA

NEW RESEARCH: Skin may hold key to neurodevelopmental disorder diagnosis

A genetic diagnostic method using a small sample of skin from the upper arm could identify rare neurodevelopmental disorders in a non-invasive way, according to researchers at the University of Adelaide.

Currently, conditions caused by a significant disruption during brain development, like Rett Syndrome, epilepsy and Down Syndrome, affect one in 50 Australian children.
But there are around 6000 rare disorders, many of which don’t have names as they are defined more by symptoms or the genetic variations which cause them.

A team at the Robinson Research Institute led by Dr Lachlan Jolly, Head of the University of Adelaide’s School of Biomedicine's Neurobiology Research Group, and Professor Jozef Gecz, Head of the School of Medicine’s Neurogenetics program, have developed a way to transcribe genetic variations into RNA to help determine if they are disease causing and therefore improve genetic diagnosis.

These findings, as part of the PERSYST Study, have been published in the American Journal of Human Genetics .
“A genetic diagnosis is a prerequisite to appropriate care, therapies, clinical trials, family planning and importantly, a community of belonging and support,” said Dr Jolly.
“What we’ve been able to do is activate the expression of brain disease genes in cells derived from a patient skin biopsy grown in the laboratory to obtain the genes RNA transcript; previously this would have only been possible through a sample of patient brain tissue, which is rarely available or advisable.

“What we’ve been able to do is activate the expression of brain disease genes in cells derived from a patient skin biopsy grown in the laboratory to obtain the genes RNA transcript; previously this would have only been possible through a sample of patient brain tissue, which is rarely available or advisable."Dr Lachlan Jolly, Robinson Research Institute, Head of the University of Adelaide’s School of Biomedicine's Neurobiology Research Group

“Activating the disease genes in skin cells enables a functional RNA based study to resolve the pathology of the genetic variant. Such individuals would otherwise often never receive a genetic diagnosis because the genes RNA is unobtainable without highly invasive procedures.

“Variants in these genes account for 22.2 per cent of all variants of uncertain pathology, which currently equates to hundreds of thousands of people world-wide living without a diagnosis, and that number continues to rise.”
This breakthrough approach underpins the PERSYST study, a national collaboration between scientists, clinicians, diagnostic laboratories and rare disease community groups across Australia. The PERSYST study, which currently runs until 2027, utilises this new skin-based diagnostic technology and has a national recruitment program for a subset of individuals living with a genetically undiagnosed rare disease.

“PERSYST is providing the critical evidence to support the genetic diagnosis of Australian individuals and their families, ending the burden of their diagnostic odysseys and providing opportunities for better care, support, and access to precision treatments,” said Dr Jolly.

A number of rare disease groups are involved in this study, including a representative from GETA (Kris Pierce).

READ MORE HERE: https://www.adelaide.edu.au/.../skin-may-hold-key-to...

CONSUMER ENGAGEMENT OPPORTUNITY

EXPRESSION OF INTEREST: CONSUMER ADVISORY GROUP FOR PSYCHOSOCIAL SUPPORT IN PRECISION

The consumer must have accessed the NSW health system.
If you have any questions, please do not hesitate to reach out to Kris Pierce via [email protected]

Background
The Psychosocial Enabling Platform offers psychosocial research expertise and support to precision medicine studies to ensure that the needs of all patients, their siblings and their families are met.
Precision medicine involves creating treatments that are specifically designed for an individual's unique characteristics, like their genetic makeup, specific biological markers, observable traits, and even their psychological and social conditions. This approach aims to improve treatment effectiveness by considering how these personal factors influence health and disease.
The platform will have an equity focus on priority populations including Aboriginal and Torres Strait Islander, Culturally and Linguistically Diverse communities, lived experience of disability, rural and regional areas and/or those affected by socioeconomic disadvantage.
Our aim is to provide psychosocial resources for families, support education and schooling for children having paediatric precision medicine and their siblings and enhance mental health in children and families accessing paediatric precision medicine.
Purpose
We are establishing this consumer advisory group to ensure that the perspectives and experiences of patients and their families are embedded into the development of supports related to receiving precision medicine. By incorporating valuable insights from those directly impacted the program will ensure the supports and resources developed are deeply attuned to the psychosocial needs of patients.
Roles and Responsibilities
Advice on Projects: Members will review and provide input on proposed projects, focusing on their relevance and potential impact on patients.
Sharing Lived Experience: Members will share their personal experiences or insights from their communities to inform and guide the program's direction.
Advocacy and Community Engagement: Members will act as liaisons between the research community and the public, advocating for patient needs and raising awareness.
Meetings
Meetings will be scheduled four times a year via online platform and will be 1 hour in length.
APPLY HERE:

EXPRESSION OF INTEREST: CONSUMER ADVISORY GROUP FOR PSYCHOSOCIAL SUPPORT IN PRECISION MEDICINE Thank you for your interest in applying to be a member of the Child Unlimited/Luminesce Consumer Advisory Group. Please find further details below. We encourage anyone with a lived experience to apply - people from the following communities are encouraged to apply, including Aboriginal and Torres St...

Global Genes interview Salvador Rico, MD, PhD, chief medical officer of Encoded Therapeutics Inc., on RAREcast and discuss the company’s lead program in Dravet syndrome, its efforts to develop gene therapies with optimized regulatory elements to target specific organs, and why he believes its approach is a point of differentiation for the company.

Differentiating Gene Therapies Through Regulatory Elements Encoded Therapeutics is developing gene therapies that can target any cell type that has a unique genetic profile. The company’s lead experimental therapy is in development for the epileptic encephalopathy Dravet syndrome, although the company expects to pursue metabolic, liver, and cardiovascular...

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Thanks to all those who participated in the GETA conference over the weekend.

There were some follow-up questions for Prof Angela Morgan on speech that Prof Morgan has kindly provided answers to:

Q: How early can we start with higher tech AAC for a child with some word approximations? making gains with KWS, but very low processing speed and seizures? 2.5 yo
A: Terrific to hear there are gains with key word sign that is a really positive indicator for ongoing AAC use. The best thing to do is to see a specialist in AAC and speech and language in your local area. If you write to us and let us know where you live – we could try to find a trusted colleague to see you. When to start really depends on a number of child based factors.

Q: Given our kids have developmental delay with a DEE diagnosis, when is the right time or age to explore apraxia or dysarthia? (My child is three.)
A: Great question. If your child seems to have greater understanding than expressive ability and has just a few sounds – it could be time to explore further diagnoses for speech.

Q: How can we do speech therapy if the child has no visible or noticeable motivator?
A: There are many different ways to interpret this helpful question. This is the type of thing that requires individual assessment. Your speech therapist and treating team need to tease out your child’s level of current communication abilities first and then go from there.

Speech and language therapy also needs targeted therapy based on their diagnosis

Understanding speech and the characteristics of each genetic condition is critical when developing clinical trial protocols.

Clinical guidelines fall short, often lacking speech and communication detail.

Sleep problems are complex and often it takes time to understand the predisposing factors and build a plan to address these.

Sleep and epilepsy are connected. More than 50% of people with DEE’s have sleep problems and sleep issues correlate to more seizures - Dr Annie Chin

We had some additional questions for Prof Petrou that we couldn't get to during the conference yesterday. Prof Petrou has kindly written responses to the questions which we've listed below:

Q: Would the way an antisense oligonucleotide (A*O) for SCN2A works be different or similar to how it works with the SCN8a gene?
A: The SCN2A A*O I talked about would be similar for SCN8A.

Q: Is there a role for A*O in stop or nonsense mutations specifically if there's only one copy of the gene ( x linked disorder)?
A: We can use A*O to upregulate genes to overcome non-sense mutations, for example, our SYNGAP1 program.

Q: What does access look like for PRAX-222 in the future for affected families? Will it likely involve out of pocket expense for families to access globally?
A: We hope insurance companies (US) / Medicare (US and Australia) will cover PRAX-222 and other treatments in the same way they cover other A*Os for rare disorders, such as spinraza for spinal muscular atrophy.

Q: How far are they looking to increase the dose of the SCN2A A*O with the next clinical trial?
A: We (Praxis) really want to fully explore 1mg at this stage as there is strong safety and great efficacy. Longer trials are needed to understand that first.

Sleep problems are common in DEEs and can be part of the underlying disorder.

Dr Annie Chiu, Paediatric Epilepsy Fellow at Austin Health

Sal Rico from Encoded Therapeutics reminds us how crucial natural history studies are to get gene therapies approved.

Dr Katherine Howell from Murdoch Children's Research Institute - MCRI is presenting a report on the impact of DEE on the caregiver.

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Sarah Webster, SYNGAP1 parent is sharing her story of raising Gracie in Outback Australia.

Professor Ingrid Scheffer is now providing an update on Developmental and Encephalopathies.

The Florey Institute of Neuroscience and Mental Health

Studies in children with autism have shown enhanced pitch discrimination and a better ability to recognise patterns in music.

Professor Phil Pearl of Director of Epilepsy and Clinical Neurophysiology at Boston Children’s Hospital and Chair and Professor of Neurology at Harvard Medical School is warming up for his presentation on Autism and the Neurology of Creativity.

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