Cognition, behavior & clinical trials in SYNGAP1

Here are our introductory comments:

Dr. Andrew Stanfield Webinar Intro 1/14/2021

We are very excited to continue the SRF webinar series. The goals of the series are:

• getting you closer to the science 
• making you aware of the research that is been done and the opportunities to participate
• and empowering your communications with clinicians 

We also want to give a plug for our next webinar which will take place on January 28th, 12 EST.  That will be with Dr. Karthik Rajasekaran on “"Cannabinoids: What do we know?"

Today’s speaker is Dr. Andrew Stanfield and his talk is titled ¨ Cognition, behaviour and clinical trials in SYNGAP1¨

Dr. StanfieldDr. Karthik is a Clinical Research Fellow, Honorary Consultant Psychiatrist at the University of Edinburgh.

Following the completion of his basic specialist training in psychiatry, Dr. Stanfield took up a position as a clinical lecturer at the University of Edinburgh. Within this post, he obtained a Wellcome Trust Clinical Research Training Fellowship to examine the relationship between the autism and schizophrenia spectrums.

Following this, he was appointed as a Senior Clinical Research Fellow in the Division of Psychiatry and Co-director of the Patrick Wild Centre.

He undertakes clinical work as an honorary consultant psychiatrist for NHS Lothian Learning Disability Services, including sessions for the Regional Autism Spectrum Disorders Consultancy Service.

He is also a founding board member of Tailor Ed Foundation, a lottery funded charity which provides behavioural interventions to children with autism.

After this brief introduction, I want to let you know a recorded version of this webinar will be available on the SRF website.

By the end of this presentation, you will have an opportunity to get your questions answered. We’d love to hear from you – please write your question in the chat.

For those of you just joining us, welcome to our talk today by Dr. Andrew Stanfield entitled ¨ Cognition, behaviour and clinical trials in SYNGAP1¨. It is now my pleasure to turn things over to Dr. Stanfield.

• Older animal models to look at whether treatments are effective.
• Trials across the age range. 

Webinar Overview:

Dr. Andrew Stanfield is the co-director of the Patrick Wild Centre, a research center for autism and intellectual disability, at the University of Edinburgh. In this webinar, he talks about the components of clinical trials, including the development stages, trial designs, outcome measures, and what is required to run a successful trial. However, even with all of the right moving pieces, there is only around a 13% chance of a clinical trial working, which Dr. Stanfield has learned from experience in his trials for Fragile X Syndrome. Dr. Stanfield explains the most critical parts of creating a successful clinical trial, including recruitment of participants, measuring the right outcomes, and taking the desired therapy from animal models in the lab to humans in the clinic, a process known as translation. He concludes the webinar by talking about his lab’s Neuro GD Study, a comparative study looking at the overlaps between Fragile X Syndrome and SYNGAP1, as well as the SYNGAP1 sleep study which will look at sleep difficulties in SYNGAP1 patients. Both of these studies will help further our understanding of SYNGAP1 in the future.

Other Relevant Publications by Dr. Stanfield

Clinical and behavioural features of SYNGAP1-related intellectual disability: a parent and caregiver description

Sleep Abnormalities in the Synaptopathies - SYNGAP1-Related Intellectual Disability and Phelan-McDermid Syndrome

Here are our final comments:

Thank you very much Dr Stanfield and all your team for the work you do . You clearly summarised the key challenges in developing clinical trials, particularly the challenges in approximating efficacy in animal models and the challenges in finding biomarkers in neurodevelopmental conditions. You also spoke about barriers in recruitment, the challenges families face in being able to participate in studies and trials and how we may innovate in that area.

• Your thoughts on data we can prepare/capture/fund to position SYNGAP1 to be best prepared for clinical trials for targeted therapeutics. Given that we as a disease are perhaps looking at trials that target the underlying cause of the disease but also may be eligible to participate in drug trials that target the common mechanisms of ID/ASD.
• In the latter part of 2020 SRF launched our digital natural history study, a retrospective longitudinal study based on electronic health care records with partners Ciitizen. Currently close to 100 US based participants enrolled. 
• We note Stoke Therapeutics recently described primary endpoints in their Dravet mRNA antisense trial (STK-001) are toxicity and pharmacokinetics, secondary endpoint is seizure reduction. Adaptive & behaviours on further open label studies (Vineland). Your thoughts perhaps on how this trial and others (Angelman GTX-102) might influence a SYNGAP1 (or even FXS) “smart” drug trial endpoints.
• We are conscious of our very small patient population, likely to be ~1000 by year end 2021 and how difficult it will be to recruit for trials. Your thoughts on the future challenges of distributed trial participation?

You spoke about the importance of participant recruitment: 

• One of the things we suffer from as a disease/disorder is underdiagnosis. I’d ask you to speak about the barriers to increasing genomic diagnosis of children and adults with learning disabilities and how we as a patient group might work to overcome this. 
• We know in the SYNGAP1 community it’s really rather rare to get a diagnosis as an adult (we have a short film coming in the next few months about the life of a 65 year old lady recently diagnosed with SYNGAP1 in New Jersey). 
• Sequencing does not seem to be as readily available on the NHS? We note from social media that UK families tell us microarray is performed but paediatrics are perhaps not always referring for further sequencing. 
• We also suffer from a lack of racial and ethnic diversity in diagnosis and this must also be true for ID genomic diagnosis in general.