P.O. Box 50030 London, ON N6A 6H8 info@rett.ca (519) 474-6877

2024 Research Grant Awarded

The Board of Directors has unanimously approved the funding of two research grants totaling $100,000 from the Hope Fund for 2024. Both projects have strong scientific merit and show promise into future Rett research. The Hope Fund was established in 2014 and, by the generosity of our community, has funded over $930,000 in Canadian research to date. O.R.S.A.’s Research Advisory Committee received and evaluated grant applications, comprised of impartial and prominent neurologists, geneticists and scientists from across Canada. O.R.S.A. would like to thank all those who applied for this opportunity. We are pleased to award funding to Dr. Wright to support research titled: “Investigating CtIP as a Genetic Modifier in Rett Syndrome” and Dr. Rossignol and Dr. LeRoux, to continue supporting their research funded by the Hope Fund in 2023 titled: Electrophysiological non-invasive biomarkers in Rett Syndrome evaluation.

Investigating CtIP as a Genetic Modifier in Rett Syndrome

Lay Summary:

Rett syndrome (RTT) is a severe neurological disorder predominantly caused by genetic mutations in the MECP2 gene. The disorder almost exclusively affects females, presents in childhood, and limited effective treatments exist. Since the disease can range in severity and age of onset, there is an active search in the research community for genes that may help explain these differences. These genetic modifier studies are essential since they can uncover new drug targets, leading to new treatments. Recent evidence from animal studies of RTT has suggested that the pathways that repair our genetic material (i.e., DNA) could be critical for modifying the clinical presentation of the disorder. The current investigation will study a key DNA repair gene in human RTT brain cells to help understand how these processes might be involved in the disease. We will take advantage of recent advances in cutting-edge technologies in genomics, gene editing and human stem cell biology to investigate DNA repair in disease-relevant cells. Findings from these investigations will provide crucial insights into disease processes in RTT and provide a platform to identify and study additional RTT modifiers. Further, such research can identify new avenues for future therapeutic interventions in RTT and other neurodevelopmental disorders.

Dr. Galen Wright, PhD

Wright Lab Neurogenomics Research

Dr. Galen Wright is an Assistant Professor and Tier 2 Canada Research Chair in Neurogenomics in the Department of Pharmacology and Therapeutics at the University of Manitoba. He is also a principal investigator in the PrairieNeuro Research Centre at the Kleysen Institute for Advanced Medicine and a research scientist at the Children’s Hospital Foundation of Manitoba. His research interests lie in the fields of precision medicine, neuroscience, and DNA repair. He completed his Ph.D. in Genetics at Stellenbosch University in 2012 and then received additional training in computational biology at the South African National Bioinformatics Institute. Dr. Wright moved to Canada in 2014 to start a postdoctoral fellowship at the University of British Columbia, where he performed precision medicine research in neurological disorders. In his independent research program, his team focuses on studying genetic modifiers of neurological disorders, with a key focus on Rett syndrome. They use a combination of large-scale bioinformatic analyses, combined with functional genomic experiments, to identify novel therapeutic targets to improve neurological disease management.

Wright Lab website https://galenwrightlab.com/


Electrophysiological non-invasive biomarkers in Rett Syndrome evaluation


This prospective single-center study, conducted at the CHU de Sainte Justine (Montreal, Quebec), aims to develop new non-invasive biomarkers of Rett syndrome progression in a pediatric cohort. Version date 11/22/2021 These biomarkers are based on functional and spectral connectivity including measurements of coherence and cortical integration in electroencephalogram, and mismatch negativity by auditory evoked potentials. Prospective data with repeated measurements one year apart will be collected in patients and age-matched controls, and disease evolution and level of severity (standardized scales as RSBQ and CGI) will be compared between both time points. These values will serve as a baseline for comparison in future therapeutic trials. Indeed, the first gene therapy in Rett Syndrome (REVEAL study, Taysha) is being launched at Ste-Justine, initially in adults, with a subsequent pediatric phase considered if the therapy is well tolerated in adults. Similar electrophysiological measurements will be conducted in the adult patients but an understanding of the evolution of such neural signatures in pediatric age groups is lacking. We thus propose to assemble a first large pediatric Rett syndrome cohort to document the natural evolution of these electrophysiological signatures over time, and to address how these biomarkers evolve with disease progression and therapies.

Dr. Elsa Rossignol

Dr. Elsa Rossignol is a pediatric neurologist at the CHU Sainte-Justine and an associate professor of clinics in the departments of Neurosciences and Pediatrics at the Université de Montréal. She is the recipient of the Canada Research Chair on the Neurobiology of epilepsy. Her research aims to clarify the molecular and cellular basis of pediatric epilepsies. Using Next Generation Sequencing in large cohorts of patients, her lab contributed to the identification of dozens of novel epilepsy genes. Furthermore, her lab uses multimodal approaches to study the network mechanisms by which mutations in these genes result in epilepsy and cognitive deficits, with a focus on their impact on network inhibition. Her recent work revealed the key role of cortical disinhibition in genetic generalized epilepsies with cognitive deficits, and the therapeutic benefits of re-establishing network inhibition on seizures, attention and cognitive flexibility. In addition, Dr. Rossignol is the Director of the Integrated Rett Syndrome Clinic at the CHU Sainte-Justine. Her clinical research on Rett syndrome aims to identify better biomarkers of disease progression, to optimize clinical scales to track disease state and to explore novel therapeutic options, including gene therapy. In particular, she is the lead PI for the REVEAL gene therapy trial for Rett syndrome (Taysha, NCT05606614). Altogether, as a clinician-scientist working in the field of rare diseases, Dr. Rossignol aims to advance care for children with genetic neurodevelopmental disorders including Rett syndrome.

Dr. Marie Le Roux

Dr. Marie Le Roux is a pediatric epileptology fellow at the CHU Sainte-Justine. She achieved her pediatric neurology residency in France, and a Master’s Degree in Neuroscience at Paris-Sorbonne University, France. She has particular interest in electrophysiology. She recently worked on high resolution EEG and source localisation in focal refractory epilepsies. Her main interest concerns electrophysiology in neurogenetic patients. She recently integrated the Rett Syndrome Clinic at the CHU Sainte-Justine. Her clinical research on Rett syndrome aims to identify non invasive biomarkers of disease progression through electrophysiology in order to help generate normative data in this population, which will serve as a baseline to compare post-therapy data in the context of future therapeutic interventions, including gene therapy.

Health Canada Accepts a New Drug Submission 

Health Canada Accepts New Drug Submission for Trofinetide

Acadia Pharmaceuticals is pleased to share that Health Canada has accepted their New Drug Submission (NDS) of trofinetide for the treatment of Rett Syndrome. Moreover, the treatment has been granted Priority Review to help expedite review timelines.

As you already know, Canadians living with Rett Syndrome, and their caregivers, lack options to treat the array of debilitating symptoms associated with this rare, neurodevelopment disorder. Should trofinetide receive Health Canada approval, it will be the first and only Rett Syndrome treatment in Canada – a pivotal and hopeful milestone for Canadians impacted by the disease.

Acadia Pharmaceuticals is committed to leading neuroscience breakthroughs and advancing treatment options for those living with rare diseases. We are excited to bring this commitment to Canada to improve the understanding of rare diseases and find solutions for life-altering conditions, like Rett Syndrome, through research, treatment innovation, and patient support programs.

19th Rett Classic Registration

Register Now Before
Friday, May 25, 2024 at 5pm

2023 October Awareness

We are to make another mark in Canada this October for Rett Syndrome Awareness Month.

Please take a look at our Awareness Month page for more information and activities.

Stronger Together Caregiver Conference

O.R.S.A. invites you to our 2023

Stronger Together Caregiver Conference

Date: October 20-22, 2023

Location: Ottawa, Ontario





Friday October 20 


7:00pm – 9:00 pm 

Meet and Greet  


Registration to obtain name tags, conference package 




Saturday October 21 





Registration to obtain name tags, conference package 





O.R.S.A. Information session 


Sabrina Millson, O.R.S.A. President 





Rett Syndrome Genetics 


Dr Victoria Siu, MD 





Transition into Adulthood 

Caitlin Cassidy, MD  




10:00 – 10:15am Break 




10:15– 12:00pm 

Medical Panel 

Renee Brannan, RN & Neurology Case Manager 


Dr Cassidy & Dr Siu 




12:00 – 1:00pm Lunch 





Communication and Literacy  


Karen Congram, Congram Education Consulting 





Communication and Literacy  


Karen Congram, Congram Education Consulting 




3:15 – 3:30pm Break




3:30 – 4:30pm 

Beyond bubble baths: Self-care for the long haul 


Julie Keon, RSSW 





Celebration Dinner 

Business Casual 


Networking and Awards 




Sunday October 22 




8:00 8:45am Breakfast 





Parent Panel  


Facilitated by Terry Boyd 




10:3010:45am Break 




10:45 – 11:30am 

What is a clinical trial? 


Dr Elsa Rossignol, MD 




11:30– 12:00pm 



Taysha Gene Therapies  




12:00pm Wrap up and Lunch 





Presenting Sponsor

Silver Sponsor

Bronze Sponsor

2023 AGM Presentation sponsored by Acadia Pharmaceuticals

O.R.S.A. would like to thank, Acadia Pharmaceuticals, for sponsoring our 2023 Annual General Meeting (AGM) and participating as our guest speaker. To hear more about Acadia’s commitment to Canada and next steps, please watch the recorded presentation. 


Survey – Parents and Caregivers Conference

Friday October 20 to Sunday October 22, 2023

Ottawa Ontario 

(venue to be confirmed)

Draft Agenda

    • Friday evening – Care Givers, Speakers and Parents – Meet and Greet

    • Saturday (full day) – Medical Panel

    • Sunday (half day) – Parent Panel


  • Please complete the short survey to assist Education and Outreach Committees to plan your next Ontario Rett Syndrome Association conference!

Acadia acquires global rights to Trofinetide

Acadia Pharmaceuticals Acquires Ex-North American Rights to Trofinetide and Global Rights to Neuren’s NNZ-2591 in Rett Syndrome and Fragile X Syndrome

– Expanded agreement follows Acadia’s April 2023 U.S. launch of DAYBUE™ (trofinetide) as the first and only drug approved for the treatment of Rett syndrome

— Acadia provides DAYBUE launch update and announces second quarter preliminary net sales and guidance for third quarter

— Company to host conference call and webcast today at 4:30 p.m. Eastern Time

SAN DIEGO–(BUSINESS WIRE)– Acadia Pharmaceuticals Inc. (NASDAQ: ACAD) today announced that it has expanded its current licensing agreement for trofinetide with Neuren Pharmaceuticals to acquire ex-North American rights to the drug as well as global rights in Rett syndrome and Fragile X syndrome to Neuren’s development candidate NNZ-2591. In April of this year, Acadia launched trofinetide in the United States under the brand name DAYBUE as the first and only drug approved for the treatment of Rett syndrome.

“This expanded worldwide agreement solidifies Acadia’s position as the global leader in addressing the unmet needs of people with Rett syndrome,” said Steve Davis, Acadia’s President and Chief Executive Officer. “We have successfully delivered DAYBUE, the first FDA-approved therapy that treats the core symptoms of Rett syndrome, and are deeply committed to broadening access to this important therapy for patients worldwide.”

In addition to expanding access to trofinetide outside of North America, this agreement gives Acadia exclusive worldwide rights to NNZ-2591 in both Rett syndrome and Fragile X syndrome. NNZ-2591 is an investigational synthetic analogue of cyclo-glycyl-proline (cGP) which results from the breakdown of human insulin-like growth factor 1 (IGF-1). NNZ-2591 is currently under development by Neuren in four other rare neurodevelopmental syndromes.

Execution of this agreement advances Acadia’s corporate strategy to expand our rare disease business. This deal also enables Acadia to leverage insights from our successful U.S. launch of DAYBUE in other global territories. In addition, this expansion will further advance the global potential of Acadia’s current development portfolio.

Acadia intends to submit a New Drug Submission (NDS) for trofinetide in Canada in the next 18 months with plans for Europe, Asia and other regions to be announced at a later date.

Financial Terms

Under the terms of the expanded agreement, Neuren will receive an upfront payment of US $100 million and is eligible to receive additional potential downstream milestone and royalty payments earned separately for trofinetide and NNZ-2591.

Outside of North America, Neuren is eligible to receive additional payments for trofinetide upon the achievement of specified revenue milestones as follows:


First Commercial Sales Milestones

Total Sales Milestones(1)


$35M (Rett); $10M (2nd indication)

Up to $170M


$15M (Rett); $4M (2nd indication)

Up to $110M

Rest of World


Up to $83M




Each region’s sales milestones are divided into four distinct milestones based upon escalating annual net sales thresholds as defined in the agreement.

Neuren will also receive tiered royalties from the mid-teens to low-twenties percent of trofinetide net sales outside of North America. In North America, all milestones and royalties for trofinetide remain unchanged from Acadia’s previously existing North American license agreement with Neuren. Potential future payments to Neuren related to NNZ-2591 in Rett syndrome and Fragile X syndrome are identical to the payments for trofinetide in each of North America and outside North America.

Preliminary Second Quarter Revenues and Updated Guidance


  • DAYBUE 2Q 2023 preliminary net sales: $21 to $23 million.
  • DAYBUE 3Q 2023 net sales guidance: $45 to $55 million.


  • NUPLAZID 2Q 2023 preliminary net sales: $140 to $144 million.
  • NUPLAZID Full Year 2023 net sales guidance: $530 to $545 million.

Conference Call and Webcast Information

Acadia will discuss the exclusive worldwide licensing of trofinetide and NNZ-2591 via conference call and webcast today at 4:30 p.m. Eastern Time. The conference call will be available on Acadia’s website, www.acadia.com under the investors section and will be archived there until August 12, 2023. The conference call may also be accessed by registering for the call here. Once registered, participants will receive an email with the dial-in number and unique PIN number to use for accessing the call.

About Rett Syndrome

Rett syndrome is a rare, complex, neurodevelopmental disorder that may occur over four stages and affects approximately 6,000 to 9,000 patients in the U.S., with approximately 4,500 patients currently diagnosed according to an analysis of healthcare claims data.1-4 Worldwide, incidence rates for Rett syndrome are similar in countries across the globe, with prevalence varying according to population size, with the number of patients in Europe estimated to be larger and that of Japan’s smaller. A child with Rett syndrome exhibits an early period of apparently normal development until six to 18 months, when their skills seem to slow down or stagnate. This is typically followed by a duration of regression when the child loses acquired communication skills and purposeful hand use. The child may then experience a plateau period in which they show mild recovery in cognitive interests, but body movements remain severely diminished. As they age, those living with Rett may continue to experience a stage of motor deterioration which can last the rest of the patient’s life.3 Rett syndrome is typically caused by a genetic mutation on the MECP2 gene.5 In preclinical studies, deficiency in MeCP2 function has been shown to lead to impairment in synaptic communication, and the deficits in synaptic function may be associated with Rett manifestations.5-7

Symptoms of Rett syndrome may also include development of hand stereotypies, such as hand wringing and clapping, and gait abnormalities.8 Most Rett patients typically live into adulthood and require round-the-clock care.2,9

About DAYBUE™ (trofinetide)

Trofinetide is a synthetic version of a naturally occurring molecule known as the tripeptide glycine-proline-glutamate (GPE). The mechanism by which trofinetide exerts therapeutic effects in patients with Rett syndrome is unknown. In animal studies, trofinetide has been shown to increase branching of dendrites and synaptic plasticity signals.10,11

Important Safety Information for DAYBUE™ (trofinetide)

  • Warnings and Precautions
    • Diarrhea: In a 12-week study and in long-term studies, an aggregate of 85% of patients treated with DAYBUE experienced diarrhea. In those treated with DAYBUE, 49% either had persistent diarrhea or recurrence after resolution despite dose interruptions, reductions, or concomitant antidiarrheal therapy. Diarrhea severity was of mild or moderate severity in 96% of cases. In the 12-week study, antidiarrheal medication was used in 51% of patients treated with DAYBUE. Patients should stop taking laxatives before starting DAYBUE. If diarrhea occurs, patients should notify their healthcare provider, consider starting antidiarrheal treatment, and monitor hydration status and increase oral fluids, if needed. Interrupt, reduce dose, or discontinue DAYBUE if severe diarrhea occurs or if dehydration is suspected.
    • Weight Loss: In the 12-week study, 12% of patients treated with DAYBUE experienced weight loss of greater than 7% from baseline, compared to 4% of patients who received placebo. In long-term studies, 2.2% of patients discontinued treatment with DAYBUE due to weight loss. Monitor weight and interrupt, reduce dose, or discontinue DAYBUE if significant weight loss occurs.
  • Adverse Reactions: The common adverse reactions (≥5% for DAYBUE-treated patients and at least 2% greater than in placebo) reported in the 12-week study were diarrhea (82% vs 20%), vomiting (29% vs 12%), fever (9% vs 4%), seizure (9% vs 6%), anxiety (8% vs 1%), decreased appetite (8% vs 2%), fatigue (8% vs 2%), and nasopharyngitis (5% vs 1%).
  • Drug Interactions: Effect of DAYBUE on other Drugs
    • DAYBUE is a weak CYP3A4 inhibitor; therefore, plasma concentrations of CYP3A4 substrates may be increased if given concomitantly with DAYBUE. Closely monitor when DAYBUE is used in combination with orally administered CYP3A4 sensitive substrates for which a small change in substrate plasma concentration may lead to serious toxicities.
    • Plasma concentrations of OATP1B1 and OATP1B3 substrates may be increased if given concomitantly with DAYBUE. Avoid the concomitant use of DAYBUE with OATP1B1 and OATP1B3 substrates for which a small change in substrate plasma concentration may lead to serious toxicities.
  • Use in Specific Population: Renal Impairment
    • DAYBUE is not recommended for patients with moderate or severe renal impairment.

DAYBUE is available as an oral solution (200 mg/mL).

Please read the accompanying full Prescribing Information, also available at DAYBUE.com

About Fragile X Syndrome

Fragile X syndrome is the most common inherited cause of intellectual disability and the most common known cause of autism. Fragile X syndrome is due to a gene mutation on the X chromosome that impacts the FMRP protein, which is responsible for regulating the synapses of nerve cells. The full mutation causes Fragile X syndrome. It is estimated that between one in 4,000 and one in 7,000 males and between one in 6,000 and one in 11,000 females have the full mutation. Generally, males are more severely affected, with approximately 50% of the females having some features of the syndrome. Clinically, Fragile X syndrome is characterized by intellectual handicap, hyperactivity and attentional problems, autistic symptoms, anxiety, emotional lability and epilepsy.12,13 Currently, there are no medicines approved for the treatment of Fragile X syndrome.

About Acadia Pharmaceuticals

Acadia is advancing breakthroughs in neuroscience to elevate life. For 30 years we have been working at the forefront of healthcare to bring vital solutions to people who need them most. We developed and commercialized the first and only approved therapies for hallucinations and delusions associated with Parkinson’s disease psychosis and for the treatment of Rett syndrome. Our clinical-stage development efforts are focused on treating the negative symptoms of schizophrenia, Prader-Willi syndrome, Alzheimer’s disease psychosis and neuropsychiatric symptoms in central nervous system disorders. For more information, visit us at www.acadia.com and follow us on LinkedIn and Twitter.

Forward-Looking Statements

Statements in this press release that are not strictly historical in nature are forward-looking statements. These statements include but are not limited to statements regarding the timing of future events. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks and uncertainties inherent in drug development, approval and commercialization. For a discussion of these and other factors, please refer to Acadia’s annual report on Form 10-K for the year ended December 31, 2022, as well as Acadia’s subsequent filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All forward-looking statements are qualified in their entirety by this cautionary statement and Acadia undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof, except as required by law.


1Acadia Pharmaceuticals Inc, Data on file. RTT US Prevalence. March 2022.2Fu C, Armstrong D, Marsh E, et al. Consensus guidelines on managing Rett syndrome across the lifespan. BMJ Paediatrics Open. 2020; 4: 1-14.3Kyle SM, Vashi N, Justice MJ. Rett syndrome: a neurological disorder with metabolic components. Open Biol. 2018; 8: 170216.4Acadia Pharmaceuticals Inc, Data on file.5Amir 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): 185-188.6Fukuda T, Itoh M, Ichikawa T, et al. Delayed maturation of neuronal architecture and synaptogenesis in cerebral cortex of Mecp2-deficient mice. J Neuropathol Exp Neurol. 2005; 64(6): 537-544.7Asaka Y, Jugloff DG, Zhang L, et al. Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome. Neurobiol Dis. 2006; 21(1): 217-227.8Neul JL, Kaufmann WE, Glaze DG, et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010; 68(6): 944-950.9Daniel C, Tarquinio DO, Hou W, et al. The changing face of survival in Rett syndrome and MECP2-related disorders. Pediatr Neurol. 2015; 53(5): 402-411.10Tropea D, Giacometti E, Wilson NR, et al. Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci USA. 2009; 106(6): 2029-2034.11Acadia Pharmaceuticals Inc, Data on file. Study Report 2566-026. 2010.12Neuren Pharmaceuticals. Fragile X Syndrome. Retrieved from https://www.neurenpharma.com/products/trofinetide/fragile-x-syndrome. Accessed July 13, 2023.13UpToDate. Fragile X syndrome: Clinical features and diagnosis in children and adolescents. Retrieved from https://www.uptodate.com/contents/fragile-x-syndrome-clinical-features-and-diagnosis-in-children-and-adolescents#H3365848815. Accessed July 13, 2023.


Media Contact:Acadia Pharmaceuticals Inc.Deb Kazenelson(818) 395-3043media@acadia-pharm.com

Investor Contact:Acadia Pharmaceuticals Inc.Jessica Tieszen(858) 261-2950ir@acadia-pharm.com



Source: Acadia Pharmaceuticals Inc.