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) |
Europe | $35M (Rett); $10M (2nd indication) | Up to $170M |
Japan | $15M (Rett); $4M (2nd indication) | Up to $110M |
Rest of World | -0- | Up to $83M |
(1) | | 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
- DAYBUE 2Q 2023 preliminary net sales: $21 to $23 million.
- DAYBUE 3Q 2023 net sales guidance: $45 to $55 million.
NUPLAZID
- 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)
- 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.
References
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.
View source version on businesswire.com https://www.businesswire.com/news/home/20230713748693/en/
Last Updated: 08/08/2023 by Steve
Survey – Parents and Caregivers Conference
Friday October 20 to Sunday October 22, 2023
Ottawa Ontario
(venue to be confirmed)
Draft Agenda
Survey
2023 Annual General Meeting
Last Updated: 08/24/2023 by admin
Acadia acquires global rights to Trofinetide
Last Updated: 08/28/2023 by admin
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)
Europe
$35M (Rett); $10M (2nd indication)
Up to $170M
Japan
$15M (Rett); $4M (2nd indication)
Up to $110M
Rest of World
-0-
Up to $83M
(1)
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
NUPLAZID
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)
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.
References
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.
View source version on businesswire.com https://www.businesswire.com/news/home/20230713748693/en/
Contacts
Media Contact:
Acadia Pharmaceuticals Inc.
Deb Kazenelson
(818) 395-3043
media@acadia-pharm.com
Investor Contact:
Acadia Pharmaceuticals Inc.
Jessica Tieszen
(858) 261-2950
ir@acadia-pharm.com
Source: Acadia Pharmaceuticals Inc.
Run4Rett – Save the Date
Last Updated: 06/23/2024 by Steve
Mark your Calendars for our Annual
SUNDAY, SEPTEMBER 22nd, 2024
Location
Richvale Community Centre, 160 Avenue Road, Richmond Hill, Ontario, L4C 5L8
Stay connected with Ontario Rett syndrome Association for more details.
Feel free to sign-up for our Newsletter to be informed by email.
2023 IRSF Scientific Meeting Review
Last Updated: 08/28/2023 by Sabrina Millson
Dear Members:
It was a pleasure to attend the International Rett Syndrome Foundation (IRSF) scientific meeting held in Nashville June 5-7, 2023. The meeting consisted of both poster and oral presentation sessions and breakout discussions focused on basic, translational, and clinical work on Rett syndrome. Between sessions, attendees had ample time to connect, break down barriers, and forge new partnerships to advance toward treatments and a cure for Rett syndrome.
O.R.S.A. was well represented and acknowledged as an advocacy partner during the 3-day meeting. Our very own Canadian researcher from the Hospital for Sick Children, Dr. James Ellis, (2023 Hope Fund Grant Recipient) presented his research and acknowledge the funding contributions made by O.R.S.A. to support his work.
Valuable knowledge was gained, and connections were made with clinicians, researchers and pharmaceutical companies. Face-to-face meeting with the representatives from both Taysha Gene Therapies and Acadia Pharmaceuticals Inc has energized our commitment to our community as new promising therapies become available. We will continue our mission to build healthy tomorrow by investing efforts in advocating for treatments to be available in Canada.
As you may have heard, the 1st patient to be dosed with gene therapy happened in Canada under Taysha Gene Therapies clinical trial. The buzz and excitement was palpable during the conference. This was a momentous day for Rett syndrome community. The potential for a treatment that addresses the underlying cause of disease and slows progressions or potentially prevents the onset of disease with early intervention is truly remarkable.
Taysha Gene Therapies Announces First Patient Dosed with TSHA-102 in the REVEAL Phase 1/2 Trial Under Investigation for the Treatment of Rett Syndrome | Taysha Gene Therapies (tayshagtx.com)
Also, Nature Medicine Published Results from Pivotal Phase 3 LAVENDER™ Study Evaluating DAYBUE™ (trofinetide) Efficacy and Safety in Patients with Rett Syndrome. Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study | Nature Medicine
Hope is alive and well for the future of Rett syndrome. With the commitment and dedication of so many, one day we will have available precision medicine where families can choose what treatment will be best for their loved one. This reality is near and I for one am extremely excited about what’s to come.
Many thanks for this opportunity to attend this meaningful meeting.
With Hope,
Sabrina Millson
AGENDA
THE KEYNOTE SPEAKERS:
Nathaniel Heintz, PhD
Katherine High, MD
Rudolf Jaenisch, MD
Jeannie Lee, MD, PhD
Huda Zoghbi, MD
Now Accepting Applications for Board of Director Positions
Last Updated: 01/24/2024 by admin
Call for Nominations: Volunteer Board Members
The Ontario Rett Syndrome Association (O.R.S.A.) is pleased to announce an open call for nominations for volunteer board members within Canada. We are seeking dedicated individuals with a passion for making a difference in the lives of individuals and families affected by Rett syndrome. Join us in our mission to provide support, advocacy, and resources to the Rett syndrome community across Ontario and Canada.
O.R.S.A. is a non-profit organization committed to improving the lives of individuals affected by Rett syndrome. We work tirelessly to raise awareness about the disorder, provide educational resources to families and professionals, advocate for research funding, and foster a supportive community for individuals with Rett syndrome and their families.
Role Description: As a volunteer board member, you will play a crucial role in shaping the direction of O.R.S.A. and driving our initiatives forward. We are specifically seeking individuals with expertise in the following areas:
Requirements:
How to Nominate: To nominate yourself or someone else for a board position, please submit the following documents to smillson@rett.ca
Selection Process: Once the nomination period has closed, the O.R.S.A. board will review all submissions and select candidates for interviews. Final board members will be chosen based on their qualifications, commitment, and alignment with O.R.S.A.’s mission and values.
Join us in making a difference in the lives of individuals and families affected by Rett syndrome. By serving on the O.R.S.A. board, you will have the opportunity to contribute your skills and expertise to meaningful initiatives, and help shape the future of our organization.
We look forward to receiving your nominations and welcoming passionate individuals to join our dedicated team.
Sincerely,
Sabrina Millson
President
AGM – Save the Date
Last Updated: 07/26/2023 by admin
Please mark off your calendars for our Virtual Annual General Meeting
on Wednesday, August 23rd, 2023 at 7:30pm.
More details to will be shared on website soon.
Feel free to sign-up for our Newsletter to be informed by email.
Taysha Rett Program Update
Last Updated: 08/28/2023 by admin
Sabrina Millson, President of Ontario Rett Syndrome Association quoted,
“This is a momentous day for the Rett syndrome community. As a mom to a daughter living with Rett syndrome and the president of the Ontario Rett Syndrome Association here in Canada, I know first-hand how this disease leads to debilitating symptoms, including difficulties in communication, mobility and breathing. The potential for a treatment that addresses the underlying cause of disease and slows progression or potentially prevents the onset of disease with early intervention is truly remarkable. We’re pleased to collaborate with Taysha Gene Therapies in an effort to bring a gene therapy treatment that could meaningfully change the lives of patients and their caregivers.”
Taysha-Gene-Therapies-Announces-First-Patient-Dosed-with-TSHA-102-in-the-REVEAL-Phase-1_2-Trial-Under-Investigation-for-the-Treatment-of-Rett-Syndrome18th Rett Classic Registration
Last Updated: 06/06/2023 by Steve
Register Now Before May 28, 2023.
2023 Hope Fund Grant Winners
Last Updated: 07/26/2023 by admin
The Ontario Rett Syndrome Association (O.R.S.A.) Board of Directors has unanimously approved the funding of two research grant totaling $150,000 from The Hope Fund for 2023. The Hope Fund has funded over $828,000 in Canadian research to date.
Grant applications were received and evaluated by O.R.S.A.’s Research Advisory Committee which is comprised of impartial and prominent neurologists, geneticists and scientists from across Canada. O.R.S.A. would like to thank all those individuals that applied for this grant.
The Hope Fund was established in 2014. The funds for this research grant were raised through donations and fundraising activities. O.R.S.A. continues to support research excellence and the development of a wide scope of Rett syndrome research across Canada.
We are pleased to award $100,000 to Dr. Ellis and Dr. Zani to support their research titled: Astrocyte-derived Extracellular Vesicles to Rescue Rett Syndrome Neurons.
LAY SUMMARY
Rett syndrome (RTT) astrocytes are less able to support maturation of synapses that interconnect neurons. Human astrocytes require the IGF1 receptor for optimal neuron support, and IGF1 is a promising RTT therapy. Astrocytes release small droplets called extracellular vesicles (EVs) containing messages in the form of genetic material called microRNA. EVs deliver the cargo to nearby neurons or into the bloodstream, and limited evidence suggests that healthy EVs rescue RTT neurons. Using ORSA and other funding, we produced astrocytes from healthy induced pluripotent stem cells (iPSC), isolated EVs and determined their microRNA cargo overlaps with those altered in RTT patient blood. We submitted a Stem Cell Network grant to test if healthy control EVs rescue RTT neuron activity.
To explore EV microRNAs as blood biomarkers for IGF1 drug treatment, it is essential to evaluate the EV cargo of RTT astrocytes. We are producing RTT patient astrocytes from stem cells and will determine which microRNAs have altered levels in RTT EVs compared to controls, and if IGF1 treatment normalizes the levels of microRNAs packaged into the RTT astrocyte EVs. The differential microRNAs corrected by IGF1 treatment will be candidate biomarkers, and their ability to rescue RTT neuron activity will be tested.
Hospital for Sick Children, Toronto Canada
Dr. Ellis completed his BSc at McGill University and his PhD at the University of Toronto with Dr. Alan Bernstein developing retrovirus vectors for gene targeting. His Post-Doctoral Fellowship studying the beta-globin Locus Control Region was mentored by Dr. Frank Grosveld in London UK. Dr. Ellis established his own research team at the Hospital for Sick Children in Toronto in 1994 with a focus on gene therapy for Sickle Cell Anemia. He subsequently developed MECP2 vectors for Rett syndrome, and vectors with reporter genes that mark specific cell types. For example, the EOS vectors express specifically in pluripotent stem cells and facilitate generation of patient induced Pluripotent Stem (iPS) cells. The Ellis lab currently uses these iPS cells in collaborative research teams to model Rett syndrome, Autism Spectrum Disorders and cardiomyopathies. New research directions concentrate on post-transcriptional regulation during human neurodevelopment, and the transfer of microRNA via extracellular vesicles. Dr. Ellis is Research Integrity Advisor at the Hospital for Sick Children.
Ellis Lab website http://lab.research.sickkids.ca/ellis/
Hospital for Sick Children, Toronto Canada
Dr. Zani is a Neonatal and Paediatric Surgeon at the Hospital for Sick Children in Toronto, Associate Professor at the Department of Surgery, University of Toronto, and Scientist in the Development and Stem Cell Biology Program at the Peter Gilgan Centre for Research and Learning, SickKids, Toronto, Canada. His clinical interests are congenital anomalies and minimally invasive surgery, and his research focuses on neonatal and pediatric conditions with high morbidity and mortality rates. The Zani lab studies extracellular vesicles (EVs), which are nanoparticles released by all cells for intercellular communication. As EVs carry cargo similar to their cells of origin, EVs can be pathogenesis mediators, biomarkers of disease severity, and therapeutic agents. Among various EV-based projects, the Zani lab has recently been investigating the signatures of EVs isolated from induced plurip
Zani Lab website: https://lab.research.sickkids.ca/zani/
We are also pleased to award $50,000 to Dr Marie LE ROUX and Dr. Elsa ROSSIGNOL, for RESEARCH PROJECT: Electrophysiological non-invasive biomarkers in Rett Syndrome evaluation.
LAY SUMMARY
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 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 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.
“We are thrilled to award the 2023 Hope Fund Grant to Drs, Ellis, Zani, Le Roux Rossignol,” said Sabrina Millson, President of the Ontario Rett Syndrome Association. “Their proposals are both innovative and promising, and we believe they have the potential to make a significant impact on the Rett Syndrome community.”
The Ontario Rett Syndrome Board