Author: Rachael Hansford

Pridopidine for ALS – promising results

Posted on July 24, 2024 by - Amyotrophic Lateral Sclerosis (ALS)

At the 10th Congress of the European Academy of Neurology (EAN) 2024, Prilenia Therapeutics presented promising results from the additional analyses of Phase II Healey ALS Platform Trial evaluating pridopidine in ALS patients. The positive results will pave the way for the Phase III trial of pridopidine.

Developing disease-modifying treatments for amyotrophic lateral sclerosis (ALS) has proved challenging. The high failure rate in ALS clinical trials is often attributed to the disease’s unclear aetiology and complex pathophysiology.

Erela Dana, Director of Neurology at GlobalData, comments: “The Healey ALS Platform Trial aims to accelerate the path to approval for ALS drugs by testing drugs simultaneously and adoptively. Given the challenges in developing treatments for this disease, the platform trial is anticipated to find an effective therapy more quickly, with fewer total participants and fewer participants on placebo.”

Pridopidine is an oral sigma-1 receptor (S1R) activator currently in Phase III for the treatment of ALS. Key opinion leaders (KOLs) previously interviewed by GlobalData highlight that pridopidine is likely to be positioned as the potential add-on drug of choice for bulbar onset ALS patients due to the potential positive effects of the mechanism on speech and bulbar function.

Dana comments: “The results presented at EAN showed significant benefits in definite, probable, and early (<18mo) ALS patients at 24 weeks follow-up for ALSFRS-R Total, ALSFRS-R respiratory, bulbar, quality of life, and quantitative speech characteristics.”

Beyond the Healey trial, Prilenia also enrolled its first patient in the National Institutes of Health (NIH)-sponsored Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) expanded access protocol (EAP2) at the end of March 2024. Prilenia is planning to use the pre-specified and additional analysis data from the Healey Platform Trial to inform its pivotal Phase III trial to further evaluate the efficacy and safety of pridopidine beyond the ongoing EAP.

If the Phase III outcomes follow the positive outcomes from the Healey study, they will pave the way for pridopidine to become a key part of the treatment landscape for ALS patients with the bulbar onset form of the disease. – Erela Dana, Director of Neurology, GlobalData

Managing drug resistant epilepsy (DRE)

Posted on July 8, 2024 by - Epilepsy

Effectiveness of cenobamate and vagus nerve stimulation (VNS) highlighted at recent EAN congress

At the recent 10th Congress of the European Academy of Neurology (EAN), two investigator-led ePresentation sessions on epilepsy outlined the effectiveness of a combination of anti-seizure medication (ASM) cenobamate and vagus nerve stimulation (VNS) in managing drug-resistant epilepsy (DRE). The combination therapy demonstrated significant improvements in seizure control, highlighting its potential as a safe and effective treatment option, according to GlobalData.

Jos Opdenakker, Neurology Analyst at GlobalData, comments: “Epilepsy is often treated in combination therapy as many patients do not achieve complete seizure control through monotherapy. Combination therapies are beneficial as they result in fewer side effects in comparison to using a single drug at a high dose.”

Research at the University of Ghent demonstrated that the addition of cenobamate to VNS treatment resulted in a worthwhile improvement in patients with DRE. The findings were supported by a case study at the University of Messina, Italy.

Opdenakker continues: “The efficacy data presented at EAN instills confidence in the combination of cenobamate and VNS for the treatment of DRE and points towards a potential roadmap of seizure control for patients living with DRE. Furthermore, the data presented by the University of Ghent, and the University of Messina may signify cenobamate’s candidacy as a monotherapy for epilepsy.”

This supports insights from the key opinion leaders (KOLs) previously interviewed by GlobalData, who have highlighted the high level of efficacy of cenobamate in clinical trials involving patients living with DRE.

There is a Phase IV open-label study currently being planned in the US, which aims to assess the efficacy and safety of cenobamate monotherapy in adult subjects with newly diagnosed or recurrent partial-onset epilepsy (NCT06453213). This is a testament that cenobamate’s potential as a monotherapy is being recognised. Furthermore, KOLs previously interviewed by GlobalData have stated that drug regulatory bodies, such as the FDA and the EMA, are considering changing the approval patterns of ASMs to allow for additional monotherapies to treat epilepsy. This is provided that the treatment has displayed efficacy in combination therapy.   Opdenakker concludes: “Given cenobamate’s success when used in combination with VNS, it is not difficult to envision a future for cenobamate as a monotherapy for epilepsy. However, further research into the combination of cenobamate and VNS is warranted to optimize treatment protocols and confirm its benefit and reliability. Cenobamate’s potential as a monotherapy for epilepsy can then be further evaluated.”

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Data challenges migraine treatment pauses

Posted on July 3, 2024 by - Headache

New AJOVY® (fremanezumab) migraine prevention data presented at the EAN

  • 4th interim analysis of PEARL real world migraine prevention study presented at 10th European Association of Neurology (EAN) congress in Helsinki
  • New sub-analysis of PEARL data highlights potential negative impact of treatment pauses on patient outcomes1
  • Sub-analysis exploring impact of treatment cessation and reinitiation on migraine prevention suggests potential rise in migraine attacks and diminished treatment effectiveness upon reinitiation1

July 1, 2024: Teva Pharmaceutical Industries Ltd announced new data from the 4th interim analysis of the PEARL migraine prevention study with AJOVY® (fremanezumab) that may challenge the rationale for treatment pauses with calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) mandated or recommended by some reimbursement authorities after one year of continuous use.

The sub-analysis from the PEARL real world data explored the impact of fremanezumab treatment cessation and reinitiation on monthly migraine days (MMD) in adult patients with episodic or chronic migraine. The data1 show that pausing treatment of fremanezumab, a CGRP-pathway mAb, may result in a potential rise in monthly migraine days (MMD) following treatment cessation and reduced effectiveness upon reinitiation compared to the first treatment cycle, adding to the burden of the individual living with migraine:  

  • Over 40% of patients experienced a rapid worsening of their migraine (>=50% increase in MMD) at Months 1 and 2 post-cessation.
  • The proportion of patients achieving >=50% reduction in MMD at Month 1 and Month 3, respectively, was 49.0% and 58.9% in the first treatment period (before cessation) versus a lower effectiveness of 35.7% and 45.5% in the second treatment period (after treatment reinitiation).

Presenting the data, Dimos Mitsikostas, Professor of Neurology, Aeginition Hospital, Medical School of the National & Kapodistrian University of Athens said “The PEARL Study analysis is significant for clinicians treating people with episodic and chronic migraine as it shows that treatment cessation and reinitiation can disrupt the progress made in managing the condition in some of them. It is important that we are guided by the evidence and adopt a more personalised treatment approach and not a ‘one size fits all’ strategy in helping people with migraine long-term.”

It is important that we are guided by the evidence and adopt a more personalised treatment approach and not a ‘one size fits all’ strategy in helping people with migraine long-term

Dimos Mitsikostas, Professor of Neurology, Aeginition Hospital, Medical School of the National & Kapodistrian University of Athens

Although leading headache societies provide guidelines and consensus for beginning and escalating migraine prophylactic therapies, robust evidence to guide therapy discontinuation is currently lacking. The European Headache Federation (EHF) guidelines suggest considering a pause after 12-18 months of continuous treatment, but if deemed necessary, treatment should be continued as long as is necessary.2  A review of literature suggests stopping prophylaxis with CGRP-pathway mAbs when there appears to be a  lack of remaining need for migraine prevention, which would be less than four MMDs.3  Differing reimbursement conditions across Europe also contribute to these inconsistencies, with some  countries mandating one-year treatment pauses, despite limited supporting data.3

“This new sub-analysis may challenge the rationale for mandatory treatment pauses and highlights the potential for these breaks to diminish the benefits achieved in reducing migraine for some patients,” said Pinar Kokturk, M.D. Vice President & Head of Medical Affairs Europe at Teva. “The PEARL study demonstrates the long-term effectiveness and safety of fremanezumab in preventing both episodic and chronic migraine in a real-world setting and underscores the benefit of treatment continuity and individualised, uninterrupted patient management strategies.”

Dimos Mitsikostas, Professor of Neurology, Aeginition Hospital, Medical School of the National & Kapodistrian University of Athens, talks to ACNR about the PEARL study

References:

  1. Mitsikostas, D., et al. Impact of Fremanezumab Cessation and Reinitiation in Migraine Management: PEARL Study 4th Interim Analysis. Presented at European Academy of Neurology (EAN); 29 June-2 July 2024, Helsinki. EAN-EPR-196
  2. Sacco, S. et al. European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention – 2022 update. The Journal of Headache and Pain. 2022 23:67
  3. Al-Hassany, L. et al. The sense of stopping migraine prophylaxis. The Journal of Headache and Pain. 2023 24:9

Kisunla (donanemab) gains full FDA approval

Posted on July 3, 2024 by - Alzheimer's Disease

Lilly’s Alzheimer’s drug is a challenger for Biogen and Eisai’s Leqembi

July 2, 2024: Eli Lilly’s anti-amyloid therapy donanemab for Alzheimer’s disease was rejected for accelerated approval last year, but the FDA has now given it full approval. The FDA has cleared donanemab-abzt, branded as Kisunla, to treat adults with early symptomatic Alzheimer’s disease, including people with mild cognitive impairment and those in the mild dementia stage of AD.

Kisunla’s indication is almost identical to the FDA-approved use for Leqembi. Both drugs need confirmation of amyloid beta pathology in patients’ brain tissue before treatment can start, and both carry a warning on the risk of amyloid-related imaging abnormalities (ARIA), which are known side effects of these antibodies that target the toxic aggregates of beta amyloid proteins.

However, Eli Lilly highlighted one advantage of Kisunla, which is that it’s the first anti-amyloid drug that allows for stopping therapy when amyloid plaques are removed – enabling fewer infusions and lower treatment costs. In addition, Kisunla is dosed every four weeks, whereas Leqembi is given as an intravenous infusion once every two weeks.

One disadvantage of Kisunla is that it is perceived to have a less favourable safety profile on ARIAs, compared with Leqembi. Leqembi’s label requires four brain MRI scans before infusions, whereas Kisunla’s requires five. The need for the extra MRI scan came after Lilly showed that an MRI prior to the second infusion led to a 25% reduction in serious ARIA cases.

Analysts have suggested that the launch of another Alzheimer’s treatment should increase the uptake of the entire class of drugs (including Leqembi and Aduhelm), due to the creation of infrastructure to support their use.

Results from the Phase 3 TRAILBLAZER-ALZ 2 trial were shared at the 2023 Alzheimer’s Association International Conference (AAIC) as a featured symposium and simultaneously published in the Journal of the American Medical Association (JAMA).

Fiona Carragher, Director of Research and Influencing at Alzheimer’s Society in the UK responded to the news:

“Donanemab is now the third drug aiming to slow down Alzheimer’s disease to be approved in the US, marking another step forward in the fight against dementia, the biggest health and social care challenge of our time. We’re proud that Alzheimer’s Society funded research over thirty years ago which identified amyloid as important in the development of Alzheimer’s disease and has led to this moment today.  

“People affected by Alzheimer’s disease in the UK will wonder what this means for them – particularly as regulators did not approve aducanumab which was also approved in the US a few years ago. There are still many hurdles before donanemab could be available on the NHS. We now need to wait for the UK regulatory authority MHRA to conduct its review of the donanemab data, and for NICE to evaluate its cost-effectiveness.  

“This drug is only suitable for people in the early stages of Alzheimer’s disease, and until we fix dementia diagnosis in the UK, only small numbers of people will get the early, accurate diagnosis needed to access the treatment if it’s approved here. Right now, a third of people with dementia in the UK do not receive a diagnosis at all, so we need to see urgent investment into the specialist workforce and equipment needed to diagnose as many people as possible.

“Donanemab is just one of nearly 130 potential treatments for Alzheimer’s disease being tested in trials, so it’s paramount we ramp up preparation for their arrival and roll-out. Alzheimer’s Society is urgently calling on the NHS to publish plans for how they intend to improve early diagnosis and deliver new treatments to the people who desperately need them.” 

Alzheimer’s Society is urgently calling on the NHS to publish plans for how they intend to improve early diagnosis and deliver new treatments to the people who desperately need them.

Fiona Carragher, Director of Research and Influencing, Alzheimer’s Society

CE Mark for Image Guided Programming Software for Deep Brain Stimulation

Posted on July 1, 2024 by - Parkinson’s Disease

Boston’s Vercise™ Neural Navigator 5 with STIMVIEW™ XT technology is designed to streamline procedure for people living with neurological conditions

Boston Scientific Corporation has obtained a CE Mark on the Vercise™ Neural Navigator 5 Software with STIMVIEW™ XT technology, which when used as part of the Vercise Genus™ Deep Brain Stimulation (DBS) Systems, can provide clinicians with simple and actionable data for efficient programming in the treatment of people living with Parkinson’s disease, essential tremor and dystonia.

“We are now using image guided programming tools to optimally define the site of stimulation while we clinically assess the patient,” said Francesca Morgante, Professor of Neurology and Eleonor Peel Chair for the study of Ageing at St. George’s University of London, UK. ”This advancement in the technology has substantially cut down our programming time and allowed to improve the symptoms of our patients in a significant shorter time.”

The Vercise Neural Navigator 5 Software, with STIMVIEW XT technology, is the latest addition to the fully integrated portfolio of image guided programming solutions for Boston Scientific DBS Systems. Developed in collaboration with Brainlab, a leading software-driven medical technology company, these tools have demonstrated a reduction in programming time by 56%[1] and provide real-time visualisation and stimulation of each person’s unique brain anatomy.

The software includes an enhanced user interface that displays patient data in a simplified format and gives clinicians access to advanced settings for increased therapy delivery. The software is designed to enable more flexibility to better manage the evolving needs of individual patients at any stage of their condition.

“Our aim is to develop tools that make a meaningful difference to physicians and to people living with neurological conditions alike,” said Vincent Sourdaine, vice president, Neuromodulation in Europe, Middle East and Africa (EMEA), Boston Scientific. “This software enables more efficiency with DBS therapy to simplify what can otherwise be a time-consuming procedure, freeing up capacity for hospitals and clinicians for more value-added tasks and to provide optimal care for patients.”

This software enables more efficiency with DBS therapy to simplify what can otherwise be a time-consuming procedure, freeing up capacity for hospitals and clinicians for more value-added tasks and to provide optimal care for patients

For more information about the Vercise Genus DBS Systems and image guided programming please visit the dedicated VN5 website.

References:
[1] Lange, F et al. Reduced Programming Time and Strong Symptom Control Even in Chronic Course Through Imaging-Based DBS Programming, Front Neurol 2021 Nov 8;12:785529

King’s Parkinson’s Charitable Fund launches

Posted on June 24, 2024 by - ACNR News, Charity

Twenty years ago, Professor K Ray Chaudhuri and colleagues wrote in ACNR about the often neglected non-motor symptoms of Parkinson’s which impact so much on a patient’s quality of life – symptoms such as pain, poor sleep, depression, anxiety, sexual dysfunction and autonomic problems.

Two decades on, the newly launched King’s Parkinson’s Charitable Fund aims to address the huge gaps in patient care which still exist, driven by the patient voice. The charity has been spearheaded by Sir Nicholas Mostyn and Professor Chaudhuri.

Sir Nicholas is one of the founder members of Movers & Shakers – a podcast about life with Parkinson’s which he produces alongside Jeremy Paxman, Rory Cellan-Jones, Gillian Lacey-Solymar, Mark Mardell and Paul Mayhew-Archer. Professor Chaudhuri is Director of the King’s Parkinson’s Centre of Excellence at King’s College London.

ACNR Publisher Rachael Hansford had a quick chat with Professor Chaudhuri at the charity’s launch recently, where he explained what they want to achieve and why it has taken so long for non-motor symptoms to be given more serious attention.

How can scientists model the human brain?

Posted on June 20, 2024 by - Alzheimer's Disease, Epilepsy, Multiple Sclerosis, Neuropsychiatry, Pain, Parkinson’s Disease

bit.bio launches ioAstrocytes

For the first time, scientists can now leverage the reproducibility of ioCells to study how the four major CNS cell types interact and contribute to neurological diseases. This enables more precise research and opens new doors for developing effective treatments.

  • Human astrocytes are key to developing effective in-vitro models of the central nervous system (CNS), enabling the study and testing of new treatments for neurological and neurodegenerative diseases.
  • ioAstrocytes, the newest addition to bit.bio’s ioCells CNS toolkit, are highly characterised and functional, offering consistent results and addressing the variability issues associated with primary astrocytes.
  • Designed for ease of use with open-source media and protocols, ioAstrocytes can be co-cultured with other brain cells, including bit.bio’s ioCells range, allowing researchers to model brain complexity and gain valuable insights into disease mechanisms and treatments.

bit.bio, the company coding human cells for novel cures and a pioneer in the field of synthetic biology, today announces the launch of ioAstrocytes. This new addition to bit.bio’s ioCells portfolio creates a toolkit for disease research that addresses the challenges of data reproducibility and enables accelerated therapeutic development.

ioCells, iPSC-derived cells for research and drug discovery, are manufactured using bit.bio’s deterministic programming technology, opti-ox, and are considered best in class for their functionality, consistency, and scalability. With 18 launches to date in 2024, bit.bio’s ioCells portfolio comprises 37 products, including ioWild Type Cells, ioDisease Model Cells and ioCRISPR-Ready Cells.

Astrocytes are a type of glial cell in the brain involved in a wide range of processes, including neural signalling, homeostasis maintenance, and immune response regulation. The significance of astrocytes for effectively modelling the human brain is frequently underestimated. Growing evidence highlights the important role of astrocytes in CNS conditions, such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, epilepsy, pain disorders, and neuropsychiatric conditions. With the introduction of ioAstrocytes, scientists now have access to defined, consistent, and functional human astrocytes optimised for co-culture with other CNS cell types.

We are excited to expand the universe of ioCells with ioAstrocytes and offer researchers worldwide access to the major cell types of the human brain. Much like building blocks, scientists can combine different CNS cell types with or without disease-specific mutations to explore their interactions. We look forward to seeing how the neuroscience community will leverage this powerful toolkit to further our understanding of the CNS and develop much needed therapies for neurological conditions.”

Mark Kotter, Founder and CEO of bit.bio

ioAstrocytes are highly defined, consistent, and functional human astrocytes, optimised for co-culture with other CNS cell types. They display stellate morphology, express key markers, and perform essential astrocyte functions such as phagocytosis, secretion of cytokines, and modulation of neuronal activity when co-cultured with CNS cells.

“ioAstrocytes represent a significant addition to bit.bio’s growing ioCells portfolio, enabling researchers to enhance in-vitro CNS models and accelerate discoveries,” said Farah Patell-Socha, Vice President of Research Products at bit.bio. “By providing highly consistent cells with essential functional properties of human astrocytes, we’re unlocking novel ways for advancing neuroinflammation research, conducting in-depth neural network studies, and performing screening and toxicity assessments for potential therapeutics.”

#Genomics
#research
#ioCells
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#astrocytes
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Urgent findings from head-CT scans prioritised by AI at NHS Greater Glasgow and Clyde

Posted on May 2, 2024 by - Acquired Brain Injury, Artificial Intelligence

First of four NHS sites roll out head-CT AI to highlight critical head injury scans

A new multi-NHS site initiative went live in April, aiming to improve radiology report turnaround times for non-contrast CT head scans by creating prioritised reporting worklists of critical findings. This will allow Emergency Department (ED) clinicians at the Queen Elizabeth University Hospital in Glasgow to make faster decisions about the care, management and discharge of patients with head injuries.

The project called ACcEPT (Assess the Clinical Effectiveness in Prioritising CT Heads) commenced at NHS Greater Glasgow and Clyde, the first of four planned NHS sites across the UK, utilising qER, the head CT Artificial Intelligence (AI) solution from Qure.ai.

In the first initial weeks of the head CT AI implementation over the 2023/24 winter period, qER analysed 651 non-contrast head CTs, detecting 128 head injuries including cranial fractures, intracranial haemorrhage (ICH), mass effect and mid-line shift within the brain. The intracranial pathologies were identified and prioritised by the qER AI solution as critical findings for radiologist review, confirmation, treatment planning and/or discharge out of ED.

“By utilising the opportunities of innovative AI to help prioritise urgent cases, we will look to deliver critical interventions whilst improving workflow and time in the ED for patients with normal scans. The study looks to provide evidence to support adoption of AI across 4 centres in the UK. We hope this will support clinical teams in decision making to deliver critical clinical care, reassurance and, when appropriate, discharge, releasing capacity and space for patients in our pressured system,” states Professor David Lowe, Professor of Health Innovation at the University of Glasgow and Emergency Medicine Consultant at NHS Greater Glasgow and Clyde.

Denise Brown, Director of Digital Services at NHS Greater Glasgow and Clyde states, “It is important to establish reliable evidence on the impact and value of AI solutions, and to determine how they best support clinical decision making. Our Digital Strategy’s Enabled by AI Programme brings together NHS Greater Glasgow & Clyde’s expertise on research, innovation and the operation of AI solutions at scale, while working closely with colleagues in academia.”

Darren Stephens, Senior Vice President & Commercial Head, UK and Europe at Qure.ai states, “This is an exciting step forward for AI in NHS Emergency Departments. Providing digital health tools that can create calm and give informed prioritisation of urgent cases to support stretched clinical teams, especially at night or weekends, is very advantageous. It may help reduce CT scan-to-reporting turnaround times and give rapid alerts of critical findings that will boost the speed of treatment given to patients.”

The ACcEPT qER study is award funded by the NHS AI Lab programme run by the NHS Accelerated Access Collaborative (AAC) in partnership with the National Institute for Health Research (NIHR). It aims to evaluate the use of AI to support clinicians analysing the CT scans of patients with head injuries, leading to faster treatments and better outcomes for patients. It will assess the value of the AI tools in situations where there is a shortage of trained radiologists to analyse the scan images, particularly during out-of-hours.

The full ACcEPT collaboration team includes: medical imaging AI innovator, Qure.ai; Hardian Health for health economic evaluation; the University of Glasgow’s Digital Health Validation Lab (DHVL), a Living Laboratory for Precision Medicine project aimed at fast-tracking digital health technologies into clinical settings; West of Scotland Innovation Hub; NHS SafeHaven; NHS Greater Glasgow and Clyde; Oxford University Hospitals NHS Foundation Trust; Northumbria Healthcare NHS Foundation Trust; and Guy’s and St Thomas’ NHS Foundation Trust.

Trofinetide for Rett Syndrome – new drug submission in Canada 

Posted on April 23, 2024 by - Neurodevelopmental disorders

23 April 2024: Acadia Pharmaceuticals Inc has announced that Health Canada has accepted its New Drug Submission (NDS) for trofinetide for the treatment of Rett syndrome, a rare neurodevelopmental disorder. Health Canada has granted Priority Review for Acadia’s submission.

“Rett syndrome is a profoundly debilitating and complex neurodevelopmental disorder that presents differently across patients and can lead to an array of unpredictable symptoms,” said Pamela di Cenzo, Vice President, General Manager, Rare Disease, Canada at Acadia. “If granted marketing authorisation, trofinetide will be the first option available to treat Rett syndrome in Canada.”

Health Canada grants Priority Review for drug submissions intended for the treatment, prevention, or diagnosis of serious, life-threatening, or severely debilitating illnesses or conditions for which there is substantial evidence of clinical effectiveness that the drug addresses an unmet medical need or provides a benefit/risk profile that is improved over existing therapies.

“O.R.S.A. is pleased that Health Canada has granted Priority Review for this promising treatment which, if approved, would be a significant step forward in addressing the unmet medical needs of Canadians living with Rett syndrome,” said Sabrina Millson, President of the Ontario Rett Syndrome Association (O.R.S.A.). “Our community of patients, caregivers and supporters are excited at the prospect of having a treatment option for Rett syndrome.”

The Health Canada filing is supported by results from the positive pivotal Phase 3 LAVENDER™ study evaluating the efficacy and safety of trofinetide versus placebo in 187 girls and young women with Rett syndrome. The co-primary endpoints were change from baseline in the Rett Syndrome Behaviour Questionnaire (RSBQ) total score, a caregiver assessment, and Clinical Global Impression–Improvement (CGI-I) scale score, clinician perspective, at week 12; both were statistically significant. The key secondary endpoint measuring improvements in communication was also statistically significant. Trofinetide has been approved for the treatment of Rett syndrome in adult and paediatric patients two years of age and older in the United States, and it is not currently authorised for sale in Canada for the treatment of Rett syndrome.

About Rett Syndrome

Rett syndrome is a rare genetic neurodevelopmental disorder that occurs primarily in females following a near normal development in the first two years of life.1,2 It is caused by mutations on the X chromosome on a gene called MECP2.3 Rett syndrome is a complex and multisystem disorder that causes profound impairment to central nervous system (CNS) function, including loss of communication skills, purposeful hand use, gait abnormalities, and stereotypic hand movements such as hand wringing/squeezing, clapping/tapping, mouthing and washing/rubbing automatisms.2

Rett syndrome occurs worldwide in approximately one of every 10,000 to 15,000 female births.4 In Canada, prevalence of Rett syndrome is estimated to be 600 to 900 patients.5 Children with Rett syndrome experience a period of developmental regression between 18-30 months of age, which is typically followed by a plateau period lasting years to decades.1-3 Rett syndrome is diagnosed based on clinical evaluation, typically by about three years of age.2,6

References

1 Fu et al. Consensus guidelines on managing Rett syndrome across the lifespan. BMJ Paediatrics Open. 2020;4:1-14.
2 Neul JL, Kaufmann WE, Glaze DG, et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010;68(6):944-950.
3 Amir RE, Van den Veyver IB, Wan M, et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999; 23(2):185-188.
4 May DM, Neul JL, Satija A, et al. Real-world clinical management of individuals with Rett syndrome: a physician survey. J of Med Econ. 26(1), 1570–1580.
5 Acadia Pharmaceuticals Inc. Data on File. Canada prevalence of Rett syndrome. February 2024.
6 Tarquinio DC, Hou W, Neul JL, et al. Age of Diagnosis in Rett Syndrome: Patterns of Recognition Among Diagnosticians and Risk Factors for Late Diagnosis. Pediatric Neurology. 2015;52:585-591.