TIMOTHY
SYNDROME ALLIANCE (TSA)
ANNUAL REPORT
FOR FINANCIAL PERIOD 1 DECEMBER 2022 TO 30 NOVEMBER 2023
2023
www.timothysyndrome.org Charity Registration Number: 1185523
CONTENTS
| 01 | Who we are |
|---|---|
| 02 | What is CACNA1C? |
| 03 | What is TSA’s impact to date? |
| 04 | How has TSA been raising awareness? |
| 07 | How is TSA improving treatment, diagnosis & care? |
| 11 | How does TSA help support the global community? |
| 13 | How does TSA provide trusted informaton? |
| 14 | What has TSA done to drive research & clinical care? |
| 17 | What is the impact of CACNA1C real-world data? |
| 19 | Why is it clinically important to screen individuals? |
| 20 | How does TSA raise funds? |
| 21 | How does TSA spend funds? |
| 22 | Thank You for your support |
| 23 | Ways you can help |
| 24 | Structure, governance and management |
| 26 | Our accounts |
WELCOME
Timothy Syndrome Alliance (TSA) is a Registered Charity in England (Charity number: 1185523) run entirely by parents and volunteers.
Our Vision:
Our vision is a world where shared knowledge and understanding lead to a cure for everyone with a CACNA1C genetic variant.
Our Mission:
Our mission is to improve the diagnosis, treatment and care of individuals worldwide with CACNA1Crelated disorders including Timothy Syndrome and LongQT8, and to support the families and carers of those diagnosed.
How we work
In order to achieve our mission our focus is on five interdependent areas of activity – raising awareness, improving diagnosis treatment and care, supporting the global community, providing information and advice, and driving research and clinical development.
By working together and collaborating globally, we can harness greater strength. Using a method of sustainable growth, our goal is to build and support our global community.
Our core values and beliefs combine to form a solid foundation for the way we approach everything we do. We are determined, supportive, empowering and we are a community.
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Raising
awareness
Driving
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clinical
treatment &
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1
CACNA1C
What is CACNA1C?
CACNA1C is a gene that provides instructions for making a protein that forms part of a calcium channel in cells throughout the body. This protein manages the movement of calcium in and out of the cell (crucial for many cells’ functions). Changes to the gene can cause changes to the protein and its ability to manage calcium movement, making it work more, less, or not at all.
What is a CACNA1C-related disorder (CRD)?
CACNA1C variants have been identified in a broad spectrum of both cardiac and neurodevelopmental disorders including typical and atypical syndromic Timothy Syndrome (TS), structural heart disease with Long QT Syndrome (LQTS), isolated long or short QTS, and isolated neurologic symptoms. This is now referred to as the CACNA1C-related disorder (CRD) spectrum that encompasses a range of clinical features caused by variants predicted to both increase and decrease channel function.
The most common symptoms include abnormal heart function, irregular heartbeat, abnormal heart structure, developmental delay, incoordination, hypotonia, autism spectrum disorder (autistic features), seizures, and attention-deficit/hyperactivity disorder.
Other symptoms include low blood sugar levels (hypoglycaemia), immunodeficiencies, endocrinological dysfunction, gastrointestinal concerns, an unusually low body temperature (hypothermia), facial anomalies, syndactyly (joined fingers or toes), mild dental, skin, eye, and hair anomalies.
What is Timothy Syndrome?
Timothy Syndrome (TS) is a sub-diagnosis of just 1 genetic CACNA1C variant with mixed neurologic and cardiac symptoms. There are two types of TS: TS1 (exon 8A) and TS2 (exon 8).
What is LongQT Syndrome (LQTS) and Short QT Syndrome (SQTS)?
Long QT and Short QT are heart conditions that affect the electrical activity of the heart, causing it to take longer or shorter than normal to recharge between beats. This can lead to irregular heartbeats, which in some cases
may cause fainting, seizures, or sudden death. LQTS associated with CACNA1C is known as LQTS 8 or LongQT8.
How common are CRDs?
CRDs are rare and their prevalence is unknown.
There are <100 cases of TS diagnosed worldwide.
Prevalence is unknown due to the rarity and recent identification of CRDs.
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IMPACT ROADMAP
Award winning awareness film ‘Timothy Syndrome Alliance’. Website built and up and running. Family Day.
2019/2020
November
43 known (living) individuals with CACNA1C variants in the world.
Preimplantation Genetic Testing approved for Timothy Syndrome.
December
2020/2021
Film production ‘Rare Disease Research Journey’ underway.
Interactive Guide for Healthcare Professionals underway.
Genetic testing approval for Genetic Epilepsy.
2021/2022
Mind the Gap Mental Health & Wellbeing counselling.
Award winning awareness film ‘Rare Strikes Back’.
First annual Awareness Day. Brain Research Conference. First intenational study investigating the effects of CACNA1C on brain development & mental health Cardiff University & Stanford University.
Best Research Partnership Award.
CACNA1C Community Registry launch.
A Cross-Sectional Study of the Neuropsychiatric Phenotype of CACNA1CRelated Disorder, November Levy et al published.
2022/2023
Approx 160 known families/individuals with CACNA1C variants in the global CACNA1C Support Group
‘The Diagnosis Challenge’ film. Wikipedia page approved. Scientific Advisory Board formed. Connect CACNA1C Global Network Conference.
Genetic testing approval for Congenital Hyperinsulinism. CACNA1C diagnosis in the UK project.
Mind the Gap Mental Health & Wellbeing counselling.
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ACHIEVEMENTS AND PERF ORMANCE
Raising Awareness
Out of more than 780 entries received, our film Rare Strikes Back earned its place among the 93 films selected for the World Health Organization (WHO) 4th Health for All Film Festival 2023. WHO staff from all over the world participated in this preselection.
Further broadening our reach, Rare Strikes Back made an appearance at the Health in Focus Film Festival, hosted by the School of Public Health at Boston University. This event featured our film and included a virtual Q&A session, providing an opportunity for meaningful dialogue on the issues addressed in the film.
The collaborative effort behind The Rare Disease Research Journey highlights our commitment to advancing understanding and awareness. This film continues to evolve, a product of the ongoing partnership between the Neuroscience and Mental Health Innovation Institute (NMHII) University of Cardiff and TSA. Significant strides have been made with the interviews conducted with families and researchers such that we have been able to share film shorts on our social media platforms to reach diverse audiences, particularly on CACNA1C Awareness Day.
Simultaneously, considerable efforts have been devoted to our pathwayfocused Educational CACNA1C Interactive Guide for Healthcare Professionals. We extend our heartfelt appreciation to OPEN Health, a leading global healthcare communications agency with extensive scientific expertise, for their invaluable contribution of 200 hours of support. As filming for case studies nears completion, we remain steadfast in our commitment to accuracy, delaying the guide's launch to ensure alignment with ongoing high-level discussions regarding CACNA1C nomenclature.
For Rare Disease Day on the 28th of February (29th in a leap year), we created a short film titled ‘The Diagnosis Challenge’. Using a montage of interview snippets, the film conveys families’ frustrating journeys, through the naming of healthcare professionals they’ve seen from first noticing that something isn't right and going to the doctor to actually receiving a diagnosis.
It is a process that can take many years, with seemingly endless tests along the way, a journey known as the ‘Diagnostic Odyssey’. Tackling this challenge is crucial to provide families with the necessary knowledge and resources. It is equally as important to empower primary healthcare professionals to be able to identify and consider rare diseases
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ACHI EVEMENTS AND PERF ORMANCE
when making a diagnosis. The film was entered in the Smiley Charity Film Awards 2024 and widely shared.
In addition to our internal productions, we have participated in two external film projects, further expanding our reach and impact. Firstly, we had the privilege of collaborating on "CEOs in Unusual Places", a short film produced at the Neuroscience and Mental Health Innovation Institute (NMHII) at Cardiff University by the Smiley Movement team, the same team behind The Charity Film Awards, an accolade we were honoured to receive last year, winning the Gold award. Through this partnership, we continue to leverage the power of storytelling. Our friends at Media Trust organised a film project to highlight the invaluable contributions of volunteers. Our website volunteer with whom we were matched through Media Trust and who has been with us on this journey since 2020, was featured in the film to accentuate the profound impact of their efforts on micro charities like ours.
Continuing to use our social media platforms to raise awareness, build lasting relationships and inspire support for our mission we joined the TikTok platform as well running some focused campaigns. Notably during the month of February leading up to Rare Disease Day our social media channels underwent an informative and engaging takeover thanks to biology student Gavriella who is based in Atlanta, Georgia, who aims to become a Genetic Counsellor.
Our Awareness Day on 1st October focused on support in its many forms complete with a takeover of Rare Revolution Magazine social media channels in the lead-up to the big day.
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ACHI EVEMENTS AND PERF ORMANCE
The best way to raise awareness and gather interest is to spread the word so we are delighted to see that our social media platforms and website are doing just that. Compared to our previous year we can evidence growth in all areas.
Organic traffic (from search engine results) to our website is more likely to be from users who are new to the diagnosis, looking for community or looking to find out more information about CACNA1C. For direct traffic (typing our website's URL directly) these users typically have a specific purpose and prior knowledge of our charity, driving them to access the website directly for support, information, and community resources. Additional signposting to our website has been successful through our collaborations, press and blog articles, plus partnerships with ERNGUARD Heart, Neurological Alliance, EURORDIS, Rare Diseases International, and Global Genes to name a few.
It is heartening to see that people are leaving their social networks and social media platforms (16.3%) to directly visit our informative website and learn more about CACNA1C. Everything we post uses the same signposts #CACNA1C #TimothySyndrome #LongQT8.
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ACHI EVEMENTS AND PERF ORMANCE
The Student Voice Prize was again on our radar this year. It is an annual international essay competition raising the profile of rare diseases within the medical field, particularly with medical students, nurses and scientists who may not come across rare diseases in their training. Both Beacon for Rare Diseases and Medics4RareDiseases host the competition together and the winner gets published in The Orphanet Journal of Rare Diseases. Our students didn’t win but we are thankful to both Hussain and Diana for submitting their essays and for their increased awareness of rare diseases in particular CACNA1C.
Finally, there have also been plenty of in-person and online opportunities to raise awareness and network including the Beacon London Rare Disease Showcase, RAREsummit23, Advanced Therapies Conference, EJPRD Networking Symposium, Gene People Leadership Symposium, Rare Disease Research Network and EURORDIS Alumni training.
Improving diagnosis, treatment and care
In January 2023 our application was approved for both Timothy Syndrome and CACNA1C-related disorders to be included as a green (diagnostic evidence level) gene on the Congenital hyperinsulinism panel R144 within the NHS National Genomic Test Directory (PanelApp). This sits alongside the Epilepsy syndromes panel we advocated for last year. These additions widen the symptom net for CACNA1C to be identified on an individual's diagnostic pathway.
As PanelApp is an open platform and knowledge base of evidence for gene-disease associations used by the wider global scientific community it is hoped these gene panel additions may influence panels used in other countries.
We continue to be members of ePAG ERN GUARD-Heart, EURORDIS, Neurological Alliance, British Heart Rhythm Society, Rare Diseases International, Genetic Alliance and Gene People, offering us invaluable access to expertise, resources, and networking opportunities, whilst empowering us to advocate effectively at both national and European levels.
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ACHI EVEMENTS AND PERF ORMANCE
This year we have worked with two global genetic testing companies, GeneDx and Invitae, to make the post-diagnostic journey easier for individuals who receive a positive CACNA1C result. Collaborating with these companies ensures patients receive trustworthy information and support resources including signposting to TSA, our community and the CACNA1C Community Registry.
Advocacy Project
As a patient advocacy organisation, we have observed a notable lack of growth in the number of individuals identified with a CACNA1C variant in the UK, compared to rapid growth globally. This year we began to question the assumption that it is because we are ultra-rare. We launched a project to investigate if there were any barriers to reporting rare diseases in the UK. Barriers hinder global diagnosis, research, development of treatments and therapeutics, recognition and support mechanisms, particularly concerning ongoing healthcare. Obtaining more information about the prevalence and incidence of CACNA1C in the UK could also help identify gaps in diagnosis and signposting where we need to focus, which in turn would aid our global advocacy efforts.
We know that CACNA1C is currently included in several gene panels used to test various clinical indications. Some are delivered by the centralised Whole Genome Sequencing (WGS) service and others are testing with alternative technologies within the Genomic Laboratory Hubs (GLHs). The data generated from both testing pathways is analysed within the GLHs but the way pathogenic variants detected through that analysis are recorded is slightly different. GLHs will hold locally derived reported variant database but in addition for WGS there is a centralised variant database called the clinical variant ark.
At present, most of this data is not shared outside of the NHS Genomic Medical Service (GMS) nor is anonymous data on variants detected shared with an international open source database called ClinVar which helps support the diagnosis of other individuals with the same genomic variants. We therefore made a significant number of Freedom of Information (FOI) requests to understand the diagnostic pathways of CACNA1C in the UK and to see how this compared with the numbers on ClinVar for the rest of the world alongside those in our global CACNA1C Support Group. Our initial requests were made in England for the years 2021 and 2022, under the Freedom of Information Act 2000, which allows the public to access information held by public authorities.
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ACHI EVEMENTS AND PERF ORMANCE
The infographic below summarises our FOI findings. In 2021 and 2022 there were 7 + < 5 individuals in England confirmed to have pathogenic or likely pathogenic (disease causing) CACNA1C variants.
TSA is only aware of two of these individuals; the individual represented with wings and the individual circled with the ring. The individual circled is the son of TSA Chair Sophie. He is the only CACNA1C individual to have been submitted by a GLH in England on ClinVar in 2021 and 2022 following a specific request from the family. The UK did not submit any of the remaining 28 individuals.
In 2023 we were unable to obtain the anonymised data from Genomics England. However, in April 2024 they confirmed there were no patients with pathogenic or likely pathogenic CACNA1C variants identified as a result of whole-genome sequencing across the three years (2021-2023).
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ACHI EVEMENTS AND PERF ORMANCE
As part of this project, we are looking at CACNA1C Variants of Uncertain Significance (VUS). Variants of Uncertain Significance are variants detected during genetic sequencing, for which there is no or insufficient evidence either for or against pathogenicity - a VUS is both a specific yet also an unspecific result. Often this is because they have only been identified in a limited number of people (sometimes only one). This is a very common situation for ultra-rare diseases such as ours. Due to low awareness, phenotypic variability, a lack of genotypephenotype correlations for atypical variants, and no extant multicentric CACNA1C cohorts, clinical genetic testing results are not influencing clinical management, with many classified as VUS. Our project confirms this.
FOI findings so far confirm more than 96 individuals in England were found to have a CACNA1C variant classified as VUS between 2021 and 2023. It is standard practice in the UK and in many other countries not to inform individuals of VUS findings. These individuals are therefore also unlikely to have received cardiac or neuropsychiatric screening.
According to the ACMG (American College of Medical Genetics and Genomics) Guidelines - who produce internationally accepted guidelines for the interpretation of variants, adopted for UK laboratories by the ACGS (Association for Clinical Genomic Science) - a VUS should not be used in clinical decision-making. If a patient is identified to have a VUS, all clinical decisions should be based on personal and family history and not on the presence of the VUS. Re-analysis in the future may establish that the VUS either is or is not Pathogenic.
TSA advocates that all individuals found to have a CACNA1C gene change, even if classified as VUS, should receive cardiac and neuropsychiatric screening due to the multisystemic effects of CACNA1C. CACNA1C-related disorder is a syndromic cause of cardiac arrhythmia that also impacts neurodevelopment. 1
It is clear there is much more work to be done to inform clinical and medical treatment. We will continue this project in 2024, incorporating CACNA1C diagnostic findings from Wales and Scotland.
- Levy, Rebecca J.; Timothy, Katherine W.; Underwood, Jack F.G.; Hall, Jeremy; Bernstein, Jonathan A.; Pașca, Sergiu P. (January 2023). "A CrossSectional Study of the Neuropsychiatric Phenotype of CACNA1C-Related Disorder". Pediatric Neurology. 138: 101–106. doi:10.1016/j.pediatrneurol.2022.10.013. PMID 36436328
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ACHI EVEMENTS AND PERF ORMANCE
Supporting our global community
The diagnosis of a rare disease emotionally impacts all areas of life. Living with a rare disease is psychologically and emotionally demanding. Lengthy diagnostic odysseys, uncertain prognoses and treatment pathways, and fears about the future can impact physical and mental health.
The focus of care however is often just managing the physical symptoms. With Rareminds we are helping build the emotional resilience and wellbeing of our CACNA1C community through our ‘Mind the Gap’ workshops and individual /couples counselling delivered by qualified, specialist therapists and designed to address the key challenges in our rare journey.
“Connecting with families in the same journey has given us hope; we realise we're not alone.”
TSA also administrates an online private Facebook Support Group for individuals and families of CACNA1C-related disorders including Timothy Syndrome and LongQT8, offering 24/7 access to emotional and practical support and information via our community.
The benefits of this are huge. It enables:
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meeting and befriending other people with the same rare disorder and similar experiences from across the world
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learning about CACNA1C
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giving and receiving emotional support
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having a place to speak openly about the impact of CACNA1C and one's thoughts and feelings learning coping skills feeling empowered and hopeful advocating to improve healthcare
“Parent and support groups like the TSA are incredible because they give us support. The exchange of experiences between families is very important because even today, 8 years after the diagnosis, almost no doctor in Brazil has been able to help us because they have never heard of the CACNA1C mutation.”
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ACHI EVEMENTS AND PERF ORMANCE
Many people find it comforting and helpful to talk to someone who has experienced the same things they are facing when they or their child have a health problem. Having a rare condition can often be extremely isolating due to the lack of people with the same condition. It can be just as challenging to be a parent to someone with a rare disease. Rare disease support groups are an important source of emotional and practical support. 'The use of such advocacy-based coping may help patients to foster a sense of empowerment, efficacy, and hope' (Ayme et al., 2008)
“I think anyone new to the diagnosis should know there are people who understand a lot as well have their own experiences which gives you comfort and support even if you‘re not quite ready yet.”
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ACHIEVEMENTS AND PERFOR MANCE
Providing information and advice
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At the beginning of the year, thanks to support from Healx the first -
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Wikipedia page for CACNA1C related disorders was approved creating: Visibility and Awareness: a dedicated page on Wikipedia increases visibility for our rare disease. It provides a platform where people can learn about CACNA1C, symptoms, research and available resources serving as a central hub where experts, patients, and advocates can contribute accurate and up-to-date details including research, and clinical trials.
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Educational Resource: Medical professionals, students, and caregivers can use the Wikipedia page as a quick reference as it provides concise information, reducing the need to search multiple sources.
Pageviews since approval:874 Monthly average:73
In addition to the information available on our website and social media channels, TSA administers an online private Patient Advisory Board with 190 members of our global CACNA1C community. It is here TSA updates and works with our community on advocacy, ongoing research, collaborations and campaigns - in fact, anything of interest to our community relating to CACNA1C and our mission. Together we aim to build upon the progress made in previous years and work towards new actions to address the priorities of our community.
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ACHIEVEMENTS AND PERFORMANCE
Driving research & clinical development
On 23 June 2023, we were thrilled to gather our global CACNA1C individuals, families, caregivers, researchers, scientists, healthcare professionals, advocates, and supporters, for our virtual languageaccessible conference. By embracing this digital platform, we ensured that everyone, regardless of their geographic location, had the opportunity to join us.
We collectively shared current knowledge and ongoing studies, exchanged ideas, and fostered collaborations to help shape the future of CACNA1C research, and improve diagnosis and care.
Our programme featured presentations by members of our Scientific Advisory Board and guest speakers, all experts in their respective fields. In addition, we had two breakout discussion rooms and a dedicated Q&A session where speakers were available to address questions. Using the inclusive Translation app, participants engaged in real-time listening or reading along in their preferred language.
With 75 registrants and 48 attendees at any one time we were aware that not everyone could join us for the entire 4.5 hours. In anticipation of time constraints and varying time zones, we recorded the presentations to be available post-event.
All six presentations from the day are available via our website with language transcripts (Arabic, Brazilian Portuguese, Chinese, English, Finnish, French, German, Hindi, Italian, Norwegian, Polish, Russian, Spanish, Turkish and Ukrainian). While we cannot guarantee perfect translation, as that is not possible with AI, our approach in preparing these
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ACHIEVEMENTS AND PERF ORMANCE
presentations has eliminated transcription errors that by definition contribute to ultimate translation errors.
We hope the conference for those attending left you feeling inspired and well-informed about the latest advancements in the field of CACNA1C, and will do the same for those yet to see the recordings. This conference was a product of collaboration and passion to understand CACNA1C. A sincere thank you to all speakers and members of the Scientific Advisory Board who generously shared their latest knowledge and understanding of CACNA1C and to Cardiff University for hosting through their conference Zoom subscription.
To the CACNA1C families and individuals – you are not alone on this journey!
The CACNA1C Community Registry (CCR), accessible worldwide, continues to increase in participants and at the end of this year had 59 individuals enrolled. This is a vitally important research tool in which all families and individuals with an identified CACNA1C gene change are encouraged to participate. The CACNA1C Community Registry has been designed with the input of clinical researchers to identify information and issues relevant to families and pertinent to developing translational research. People are unique genetically and even though everyone in our community has the same gene in common, not everyone has the same genetic variant. Genetic variants are not the same - they don't necessarily act in the same way and they might have different mechanisms in terms of how they are treated. As variants in CACNA1C are so rare clinicians may only see one or two individuals in their lifetime, and therefore gathering global data is vital to understanding the natural history and
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ACHI EVEMENTS AND PERF ORMANCE
features of the condition. We are working with our SAB to analyse the Registry data and see how this can be published as research and used to inform clinical and medical treatment.
Preliminary findings from those who consented to participate in the CACNA1C Community Registry between June 10, 2022, and May 5, 2023 were presented at the Connect CACNA1C Global Network Conference and have been summarised on the poster (next page).
In November and April, we were successful in being selected, together with members of our SAB, to attend ‘Collaborating for Change’ Rare Neurology/CNS Partnering Events held at The Royal Society of Medicine, London. The “speed-date” style networking events build collaborations between patient groups, and pharmaceutical and biotech companies interested in finding treatments for rare diseases that affect the brain and nervous system.
As our community grows epilepsy and seizures are seemingly becoming a more common symptom. To understand more we are now part of the GW4 Epilepsy Community, which links researchers and clinicians aiming to improve research models, diagnosis and treatment of epilepsy. They are studying ion channel mutations, like CACNA1C that cause epilepsy using brain tissue from epileptic patients, genomics, electrophysiology, fly and computational modelling. PhD student Sophie, funded by Bristol University, will study the role of CACNA1C voltage-gated calcium channel signalling in epilepsy and Alzheimer’s disease using fruit fly models in Dr James Hodge’s lab. Epilepsy is the most common primary neurological disorder worldwide and is a co-morbidity of Alzheimer’s but what is the connection? They wish to test genes like CACNA1C that might contribute to both.
TSA is now a patient and public involvement and engagement (PPIE) member of Bristol Neuroscience Research Hub in Neurodevelopment (ND). The Network supports strategic planning and networking across the University of Bristol, two Bristol NHS Trusts, GW4 and Industry partners through collaborative research, planning funding bids and events.
Continuing with epilepsy TSA are now part of UK Rare Epilepsies Together (UKRET) a network of patient support groups and charities representing all those impacted by rare and complex epilepsies across the UK.
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The impact of CACNA1C real-world data: CACNA1C Community Registry (CCR) design Sophie Muir111, Joshua Henderson121 111 Timothy Syndrome Alliance ITSAI, UK121 Pulse Infoframe, London. Onlario, Canada The CACNA IC Community Registry is a patient registry lor all CACNAIC gene related conditions, managed by Timothy Syndrome Alliance ITSAI and powered by Pulse Inlolrame. The purpose ol the CACNAIC Comrnunity Registry is to obtain insights to better characterise CAGNA Ic-related disorders, including Tirnothy Syndrome and LongQT8. and their presentation, rnanagement and treatment. The registry was launched in June 2022 and is available lor worldwide participation. This decentralised registry is not tied lo a sile and enables anyone, anywh&re in the world with a CACNAYGrelaled disorder to sign up lor the rggistry and partieipatg from their home. REGISTRY AIMS ' Allow r9searcbgrs to stutyiyJmmDn awect8 Demographlo8 Overvlew of ourrent 8ymptom8. Variat% in CACNAIC. Inciea8e thg Vl8ibhryQt CACNAIC8olho8Q navtIng many hgarth concems rnay be thiough roseaich ar cllnlcal tr1818. Dtstumgnt h¢wdi11grfjnt Yananl$ PT¢Sgntwith differgnl syfflpt0rn8 outcom88. I A681st roseaichgrB onydhere h ihev40rfd intoi&yt•d h gludwNJ vadatlons In Ihlg 9Bn•. &ywO1 prooknmj 53.1% 34.4Y• pirUGlpint pirtWpint 18.8° ESTABLISHING CACNAIC COMMUNITY REGISTRY ENTIkn8LW4CtlhDTs, r¢i• Ihroall ++i+#+ 15.6°/0 TSA sei Out 10 cieaie a paiient ieglBtryto haiv Intr•aÈè thè vigibilily ol CACNAIGièlhiÉd Ey•J IWlh¥TrWWI 15.6% re8oaich Inlolhis group ol rare genellc aorders. Tho Pulse Infoliama plaiioim 101k6 agovornA Iiampwoth thtyi •llOVI$ 0918 b$ colÈct•d an hou8ed from mulli81119renI rare dlsgu8e communiiieB. AB B resull, regearchgrB Bre enabhd io &tUdy mull condbtlong. T0 capablllilè$ Pulse In141r4my thg 941 ¢1&19 lo iwilo lh8 CACNAICCornmunily Fegislry. W11h Ihl8 partno18hip, Pul80 Inloliamo and Timoihy syn¢T0 Allian¢• hopo 10 l•clllt810 bott91 r•wwth Iyrlhg GACNAlCcoThnvn1IV. Dillerenl vananlg onlNs #arno yne piesenl V81ieiy ol ouknme9. BY11&¢thi9d3EOon ono piotr0(m. TSA ar 1ow•r¢h$rs ¢•n palienls anywhure In the woild hus provgll to be crltlca4 when Jtudylry dIwaS w41h Palieni p4rllGlp•nls und•r p•rllclp•nls ovw th• 49• 011 9.4Y• 25% Gender Iiiii'111 46.9V• 12.5° 75010 male 250/0 female 18.8° A90 at Dlagno¥l$ PRELIMINARY FINDINGS 46.9Y• aro baséd upon individuals wrth ¢MAIC- relaioddisThd815 ICRDI who conseniad lo participale In the CAGNAICCommunity Regtry bètwèèn Junè 10. 2, and May 5, 2U23. Through May S, 2023. 43 IndlvlduaL4vdllh CRD ¢QnBented lo rtlpte In th8 regi¥try, ol 32 comw•tso lorm8 thai prov•d Infoimation on demDprathKs, Clin1 charocterL4llc8. and ufwi¢w owmpb)m64r 34.4Yo wiopJy> 25¥. 28.1% Dai& P8•t•d hor• Ar• baÈ4don thgw 32 partKipanlB. AsolJuTb8 2Q24 th0r• 810 78 p8rfK4pgrf$ in tho CACNAICCommtsnlty R•glstry. 6.2Y• CONCLUSION Age at Flrst Symptom 9.4% Familitrs Wrth 8 CACNAIGv8n8IH 18¢• m8nydillicu1tS. IndLQin9 havkn9toedu¢ai& many h9all1[g p[ofessnlS thgcond1ii. They 8iaohavè limrtÈd trèètm6ntQPlHJny Continuad enrollrnoni partlclDatKn In lh& CACNAIC rggstry will hglp th069 allgded bya vari*Kxl ¥nd re9e8ichers in ihisoènè in mwy WAYS". J Increaje uer¥Ir19of all CAcNA1&reted d190rders ErthU¢& •lll&ntAnd timè1ydkgwD% En8blp progrgss In rfys9h Facilrtate Ihedevelopment ol trealrnenlslLY CACNAIGielated dlsorder3 9.4°A At tslrth sr andll 50% pro•) 9.4% PsprI11 Communlty è9lÈtry ulse infoframe HBIBd Ghanty nD i15 SCAN ME
ACHIEVEMENTS AND PERFORMANC E
We joined UKRET rare epilepsy members with our respective scientific advisors for a first-of-its-kind Patient Advisory Group Roundtable meeting with Genomics England (GEL) to discuss the GEL service offering and potential for data access for research to address the unmet needs of our patient communities.
In January our scientific poster (next page) was accepted at the London’s Festival of Genomics & Biodata, the UK’s largest annual life sciences event. In October it was part of RAREsummit23, an event that brings all stakeholders in rare diseases together as equals to drive patient group, researcher and industry partnering opportunities and our abstract has been accepted for the British Paediatric Neurology Association (BPNA) Conference in January.
In May we were honoured guests at the University of Cardiff launch of the innovation institute where we presented on our collaboration with the NMHII to date.
Supporting the mission of TSA Sophie (Chair of TSA) is a Working Group Member of the Rare Diseases Research Network (RDRN), a partnership project between CamRARE and Patient Led Research Hub, funded by the National Institute for Health and Social Care Research (NIHR) and sponsored by Cambridge University Hospitals NHS Foundation Trust. The project aims to support the rare disease community in building an online network of partnerships and resources to facilitate new patient-centred research opportunities.
- Finally, the Voltage Gated Calcium Channel Collective (VGCCC) has formed, a collaboration of the ten CACNA1 channel patient advocacy groups dedicated to raising awareness and promoting collaboration across the voltage-gated calcium ion channelopathies.
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ACHIEVEMENTS AND PERF ORMANCE
Funding/Fundraising
Our total income for the year was £21,405, compared to £10,005 in the previous year (2021/22). This represents an overall increase of 114%, however, this was not experienced evenly across all sources of income. Support through voluntary donations continues to be a challenge due to low awareness of ultra-rare diseases compared to more well-known rare diseases hence low audience numbers, and because many of our supporters are families caring for children while also managing the cost of living crisis.
That said, a wonderful selection of Facebook birthday and activity-based fundraisers, one-off and regular gifts raised £3,483 of income to support our community and projects. Unrestricted income such as this allows us to direct funds to those aspects of our work which will have the greatest impact on achieving our global goals. We have been deeply touched by your support. We couldn’t do what we do without you. Thank you. We have the tools to raise funds from an international audience as well as those in the UK. GlobalGiving allows tax-deductible giving for donors who are US taxpayers, and JustGiving accepts donations in five default currencies, which eliminates bank currency conversion fees and makes the donation process more cost-effective. Moving forward, we will increase communication of these options.
Restricted income from grants, as well as a restricted donation, was £17,922 (2021/22: £4,706). We would like to extend a special thank you to the following trusts and foundations who have given grants during this financial year:
The Waterloo Foundation for their committed three year support of the CACNA1C Community Registry enabling meaningful change for our existing and future CACNA1C community.
The Stanley Grundy Foundation for funding the translation service. Their generous support enabled our conference to be inclusive, accessible and global.
‘Mind the Gap’ Mental Health & Wellbeing Support. This work has been made possible by an award from Postcode Local Trust, a grant-giving charity funded entirely by players of People’s Postcode Lottery.
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ACHI EVEMENTS AND PERF ORMANCE
The Renishaw Charities Committee for supporting the Educational CACNA1C Interactive Guide for Healthcare Professionals.
Our total expenditure for the year was £12,305 an increase of 161% on the previous year. The mix of spending included: CACNA1C Community Registry (66.3%), community Mental Health and Wellbeing support (9%), Connect CACNA1C Global Network Conference (9.8%), Interactive Guide/Rare Disease Day film (7.5%) and other charitable activities eg. alliance memberships, website (7.1%).
Restricted funds remaining in the account (£10,982) are for the upcoming annual CACNA1C Community Registry and further ‘Mind the Gap’ Mental Health & Wellbeing Support with our partners Rareminds.
In the next financial year the current unrestricted funds (£8,114) will assist with the remainder of the annual registry payment alongside an anticipated Speech and Language Research project we are finalising and for which we will need to source additional funding support.
Income £21,405
Voluntary Receipts
Restricted Income - grants
Expenditure £12,305
CACNA1C Community Registry Mind the Gap Support ConCACNA1C Conference Interactive Guide/RDD Film Charitable activities Governance costs
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THANK YOU
We would like to express our gratitude to our anonymous donor for supplying this specialised and adjustable classroom seat designed to promote strength and independence for one of our families. We also want to thank Gardiner Bros & Co (Leathers) Ltd for covering the shipment costs from the UK to the USA.
We sincerely thank our anonymous donor for their generous gift towards our registry payment. Your support is vital to our mission's success. Thank you.
TSA is a small charity punching above its weight and making a significant impact despite limited resources. This is made possible thanks to the people and organisations who help fund our work and provide pro bono support through internal resources and dedication of time and energy. Thank you to all of you, as well as to those we have mentioned throughout this report and our Scientific Advisory Board members, for their dedication to understanding CACNA1C.
Our voice wouldn’t be as strong without the support and engagement of our CACNA1C community. Besides sharing stories and photos which greatly helps signpost new families, encouraging and supporting each other, attending our conferences, supporting our social media channels, joining the registry, and contributing to research, they make the impossible possible. Thank you. We are Stronger Together.
As we enter 2024, we are thrilled to announce that we have been selected as the Healx Charity of the Year. We look forward to making an even greater impact together.
This Annual Report was designed and created with love at no cost to TSA
22
WAYS YOU CAN HELP
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23
REGISTERED CHARITY NUMBER: 1185523 TRUSTEES: Sophie Muir – Chair Galina Gardiner Nick Muir Meg Mcloughlin Katherine W Timothy REGISTERED OFFICE: 8 Butt Street, Minchinhampton, Gloucestershire GL6 9JP
For the year ended 30 November 2023.
Objectives: To relieve the needs of those affected by deleterious CACNA1C gene changes resulting in CACNA1C-related disorders including Timothy Syndrome and Long QT8, their families and carers worldwide in particular but not exclusively by:- (1) Promoting greater understanding of the causes, symptoms and treatment of CACNA1C-related disorders including Timothy Syndrome and Long QT8, by the promotion of research and sharing and disseminating of the results of such research for the benefit of the general public; (2) Raising public awareness of the symptoms, needs and related medical conditions of those living with CACNA1C-related disorders including Timothy Syndrome and Long QT8.
Structure, governance, and management: Timothy Syndrome Alliance (TSA) is a registered charity number 1185523, governed by the Charities Act 2006. The charity is a Charitable Incorporated Organisation registered on 27 September 2019 under the Foundation Governing Document. The Trustees delegate the charity’s day-to-day management to Sophie Muir. Trustees met four times during the year and corresponded regularly via email and other digital means, particularly to keep financial performance under review. New trustees are appointed by the serving trustees, considering the skills required by the board. Trustee induction includes online training (NCVO) to give an overview and understanding of charity governance, regulation and best practice alongside Essential Information for Trustees from the Charities Commission.
Public Benefit: The Trustees confirm that they referred to the Charity Commission's general guidance on public benefit when reviewing the Charity's aims and objectives for the year. Public benefit has been achieved through the activities outlined in the Achievements and Performance section of this report.
Reserves Policy and Going Concern: The charity receives funding for specific purposes which are restricted funds – these are not available for expenditure on other purposes. The general reserves are the unspent unrestricted funds of the charity. The charity currently owns no fixed assets, so the general reserve is held in cash. The general reserve is therefore the free reserves of the charity plus any designated funds, also termed ‘unrestricted funds’ in the charity’s balance sheet.
The purpose of the general reserve is:
a) fund shortfalls when income does not reach expected levels.
b) fund unexpected expenditures, for example when projects overrun or unplanned events
24
occur.
c) ensure that the Charity is not unnecessarily holding back on spending in favour of using the resources it has to meet its charitable objectives.
We assess the level of general reserve needed by looking forward and considering the risks to our funding balanced against our expenditure commitments. Future plans show levels of committed expenditure for which we are seeking funding, but to ensure we can continue to operate in accordance with our plans, we hold a general reserve in the range £1,500 - £2,000 to cover unfunded committed costs for the next 6 months.
Our general reserves on 30 November 2023 were £8,114 (of which £2,000 will go towards the registry fees and £4,000 towards a Speech and Language Research project), leaving £2,114 of Free Reserves which is slightly over policy. Our reserves policy is reviewed annually and updated as necessary.
The trustees have reviewed the circumstances of the Charity and consider that adequate resources continue to be available to fund its activities for the foreseeable future. The trustees are of the view that the Charity is a going concern.
Trustees' responsibilities statement
The trustees are responsible for preparing the trustees' report and the financial statements in accordance with applicable law and United Kingdom Accounting Standards (United Kingdom Generally Accepted Accounting Practice).
The trustees are required to prepare accounts for each financial year, which reflect the receipts and payments of the charity and the surplus or deficit of income against payments for the year.
The trustees are responsible for:
• keeping proper accounting records which disclose with reasonable accuracy at any time the financial position of the charity and to enable them to ensure that the financial statements comply with the Charities Act 2011, the applicable Charities (Accounts and Reports) Regulations, and the provisions of the Trust deed; and
• safeguarding the assets of the charity and hence taking reasonable steps for prevention and detection of fraud and other irregularities.
Approved by the trustees on .................. and signed on their behalf by 8 July 2024
Sophie Muir - Trustee (Chair)
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CHARITY COMMISSION FOR ENGLAND AND WALES 1185523 Recei tsand ments accounts CC16a For th• p•rk>d frorn 0111212022 To 3011112023 Section A Receipts and payments Unr•$trictod lund• Rostrictod lund• Endowm•nt fund¥ to th• nMrnt£ Total funds L•st year A1 R•c•l Vc4urrtary Rec8yB 1413 17.•22 21,408 10,1)06 ro in¢e AR) 17,•22 21,40S 10,IbM L•bl• . 21.4 A3P• m•Tr¢• G)9t of CMflt3bb8 Sub tal 1.JlS 10.•40 12.3DS 4,71X A4 A•••t and Inw8lm•nt Sub tot•1 1,365 10,940 12,305 4.701 Net of rece1ptp8yM•nts) AS Tr•n•r9 tw••n funds A6 Ca•h funds last y•u •nd Cash lunds thls y••r •nd 2,118 8.982 9,100 5399 10,982 1•,096 9,998 26
Section B Statement of assets and Ilabilities at the end of th8 p8rlod Unrnstrbct•d R•rIe1•d lund• lund Endowm•nt lund D•t•ll• 10 rn•r••l£ to n•rnt£ 81 Cash fund• 0.114 10.•02 Total c•sh lun¢ts 8.114 10.982 x1x¥6)I Unv••trlcl•d lundi R•8trtct•d lund• n•ar••t £ Endowm•nt nd• to n•uMt£ 82 (Xh•r mon•tary aM4ts Fwd to wNch Cwt l•pODn wN¢ Cott 84 AM4t• r•taln•d for lh• own u• Fwd tt Thkh Tllh•n du• Dolai15 85 Uabllhl• Skjned by on• bthalT ol al th• Signatyre Prnl Name Date of val G*4 G¥dln 8 Jul 2024 27