At the WORLD Symposium 2020, Cure Sanfilippo Foundation Chief Science Officer Cara O’Neill, MD, FAAP, and Research Projects Coordinator Elise Drake, PhD, gave a poster presentation entitled “Parent Prioritization of Meaningful Treatment Targets for Sanfilippo Syndrome,” on a subset of the findings from the Foundation’s larger Caregiver Preference Study.
The poster presentation reported survey results on caregiver priorities for meaningful treatment benefits for Sanfilippo Syndrome. It drew heavy interest from the patient advocates, scientists, NIH and FDA staff, and industry partners in attendance.
(as a printable .PDF file)
METHODSThe study used the following methods:
- A Best-Worst Scaling (BWS) case 1 experiment was conducted via an online survey of caregivers of children with Sanfilippo syndrome.
- BWS methodology elicits preference weights for different attributes—in this study, features that represent the impact of Sanfilippo syndrome. Features were selected based on previous qualitative research which identified highly-valued treatment targets of Sanfilippo caregivers.
- Participants completed 12 choice sets to select features that they considered most- and least-important to address in the context of a non-curative therapy. Figure 1 depicts an example of a BWS choice set item.
- Subgroup analysis was conducted based on child’s age and caregiver ratings of their child’s disease-specific symptoms. Log-odds importance weights were estimated using random-parameters logit for age group (6 or younger vs 7 or older) and stage (early/mid vs later) based on symptom progression. Due to small sample sizes for Sanfilippo syndrome subtypes C and D, only simple scores (i.e., best-worst scores) were calculated for sub-type analysis. Cluster analysis allowed for estimates of a child’s disease stage based on a combination of caregiver-reported cognitive ability, self-feeding ability, and autistic behaviors.
RESULTSThe poster reported the following results based on insights from 164 caregivers of children and adults with Sanfilippo syndrome from 14 different countries who completed the Best-Worst Scaling item sets.
BWS Results by Child’s Age:
BWS Results by Disease Stage:
- Across both age groups, features with highest importance weights were having pain and unsafe behaviors.
- Hyperactivity and communicating “no” were significantly more important for caregivers of younger children. Trouble getting around, sleep, and unsafe behaviors were significantly more important for caregivers of children aged 7 and older.
BWS Results by Disease Sub-Type:
- Pain and unsafe behaviors remained the most prioritized features across stage of disease.
- Caregivers of early/mid-stage children were significantly more likely to prioritize aggressive/impulsive behaviors, paying attention, feeling frustrated, and following directions than caregivers of later stage children.
- Caregivers of later-stage children prioritized trouble getting around, worry/anxiety, sleep, and sharing feelings, significantly more than caregivers of early/mid-stage children.
- Simple scores reveal caregivers of children with Type A and B similarly prioritized having pain, unsafe behaviors, and feeling unwell.
- For Type C, caregivers prioritized aggressive/impulsive toward others, not enough sleep, and having pain.
CONCLUSIONCaregivers’ relative treatment priorities reinforce the multi-symptom impacts of Sanfilippo syndrome.
The top set of prioritized features span several domains:
Pain and safety, two areas important to child and family quality of life, were most prioritized. Though there were differences by age and severity that reflect the child’s changing needs and function as the condition progresses, overall caregivers’ priorities for disease stage features were fairly consistent.
- Health: pain, sleep, and feeling unwell
- Behavioral: hyperactivity, unsafe and aggressive/impulsive behaviors
- Motor: trouble getting around
- Communication: communicating “no” and sharing feelings back-and-forth
Additional research targeting the rarer subtypes C and D may elucidate whether there are distinct treatment priorities of those caregivers.
This study provides insight into caregivers’ treatment priorities that will help inform development of therapeutics. Results here indicate that targeted, non-curative therapies that extend beyond global cognitive ability are highly valued by caregiver participants.
(as a printable .PDF file)
Cara O’Neill of Cure Sanfilippo Foundation with Tiina K. Urv, PhD, Program Director for the NIH’s Office of Rare Diseases Research.
OUR THANKSThe Foundation is grateful to the parents of children with Sanfilippo syndrome for participating in this study. Additional thanks to the Foundation’s Advisory Committee for its valuable input and to BioMarin, Lysogene, Sobi, and Orchard Therapeutics for their kind funding support.
Contact UsIf you have questions about the Parent Prioritization of Meaningful Treatment Targets presentation, contact Dr. O’Neill at Cara@CureSanfilippoFoundation.org.
Cure Sanfilippo Foundation joined 72 other patient- and disease-advocacy organizations in voicing support for a strong national Open Access policy that would guarantee immediate, free access to and full reuse of the results of scientific research that our tax dollars support in a joint letter to the Trump Administration.
The U.S. government funds more than $60 billion in scientific research each year on behalf of the public. Making sure that the results of this research are readily accessible to all citizens will speed the pace of scientific discovery, spur innovation, and, most importantly, give patients and their families hope of finding cures to rare and currently untreatable diseases.
The letter urged the Administration to issue a policy that eliminates the current 12-month
delay on articles access, and to ensure that articles and supporting data resulting from
taxpayer funded research be made immediately available under terms and conditions that
allow their full reuse.
Read the full letter here.
The letter was coordinated by Genetic Alliance, a group that engages individuals, families, and communities to transform health.
Cure Sanfilippo Foundation has an ambitious plan for the next three years:
5 clinical trials, treating 100 children, to prove at least 1 effective treatmentAmazing things have happened in the six years since the Foundation was created because of the generosity of tens of thousands of people and the hard work of families and friends of children with Sanfilippo around the world.
Last month, the research institute TIGEM presented preliminary results of two studies funded by Cure Sanfilippo Foundation at the Conference of Telethon Fundamental Associations in Italy.
So much progress toward a cure has been made. But there still isn’t an approved treatment or cure at this time. Yet.
We have an ambitious plan to bring more clinical trials to children in the next three years. AND YOU CAN HELP MAKE IT HAPPEN.
The Three-Year Plan:
By driving the pace of science, we will find a cure in this lifetime.
The remarkable support, progress, and need inspired the Foundation to create an audacious plan for the next three years. Because the supporters and families have proven that achieving bold goals is possible.
Clinical trials are where the rubber meets the road, scientifically. It’s the crucial step of determining
whether earlier research is able to show the same therapeutic benefits in people.
There are no shortcuts in science.
A cure requires significant resources. The daring price tag for this initiative is $10 million.
It’s a big goal. But it can happen with support.
Despite these dramatic costs, Cure Sanfilippo Foundation is finding
innovative and collaborative ways to support and conduct clinical trials, as
well as research.
These strategies make your donations go further. It makes $10 million help even more children, and with an effective treatment, potentially thousands.
The Future You Give BackWith a cure, families like these can dream of the future again.
How You Can HelpYour support, now and tomorrow, gives children the chance at life.
Every donation is deeply appreciated. And a multi-year commitment ensure the Foundation can achieve this plan to bring about these clinical trials in three years.
About the Foundation
Cure Sanfilippo Foundation leads in driving research to accelerate discovery of a cure for Sanfilippo Syndrome. In just six years, generous donors like you have enabled Cure Sanfilippo to generate more than $8 million through grassroots and viral fundraising to support and/or architect 20+ research projects globally, including several clinical trials.
The Foundation’s exceptional thought-leadership enables us to chart a progressive course to find a cure.
Cure Sanfilippo partnered with TIGEM (Telethon Institute of Genetics and Medicine) on research projects to explore re-positioning and re-purposing FDA-approved compounds to determine if identify they can activate the clearance of pathologic lysosomal accumulation in MSD cellular models independently of the missing enzyme in each particular disease.
Posters were presented by TIGEM at the conference for both projects. Further work to determine efficacy and proper concentration doses and delivery is ongoing in animal models and efficacy.
The team developed a new high-content screening assay to determine lysosomal activity. They have identified similar primary “hit compound” in MSD and MPS IIIA. The same compound in the screening reduces cellular heparan sulfate GAGs in cell models for MSD and MPS IIIA.
Read more about each specific research project:
Fellow Sanfilippo Advocate Katia Moletta (mother to Francesco, MPS IIIA) was able to be attend the scientific meeting and connect with the presenters from TIGEM.
Adam Shaywitz, MD, PhD, has joined the board for Cure Sanfilippo Foundation, bringing additional scientific and treatment development expertise to the organization.
“We are absolutely thrilled to welcome Adam to the board and are grateful for his support of the Sanfilippo community over the years,” said Cure Sanfilippo Board member Valerie Byers, PhD. “His extensive experience in the drug development process for devastating rare pediatric conditions will provide the Foundation with unique and invaluable guidance as we aim to accelerate our impact in the space for children with Sanfilippo Syndrome.”
Adam received his degrees from Harvard Medical School and trained in adult medicine at Massachusetts General Hospital. He subsequently pursued a fellowship in endocrinology, diabetes, and metabolism jointly at the Beth Israel-Deaconess Medical Center and Joslin Diabetes Center where he concurrently pursued postdoctoral studies in molecular physiology.
Adam is Chief Medical Officer (CMO)-in-Residence at BridgeBio Pharma, where he currently serves as CMO for three subsidiary companies: CoA Therapeutics, Aspa Therapeutics, and Adrenas Therapeutics.
Prior to BridgeBio, he spent five years at BioMarin Pharmaceutical as an Executive Director in the Clinical Sciences group. While at BioMarin, Adam developed, designed and led natural history and clinical studies for Sanfilippo Syndrome. Additionally, he played a key role in developing a number of programs aimed at treating a broad range of diseases, including other lysosomal storage disorders. During his tenure at BioMarin, Adam also worked closely with the research and business development teams to develop and broaden the pre-clinical and clinical pipeline.
“I am honored and excited to continue working with the Sanfilippo community in their mission to identify therapies that could make a meaningful impact to patients and families suffering from this devastating disease,” said Adam Shaywitz. “In addition to the urgency and drive that Cure Sanfilippo Foundation brings to their mission, they also possess a sophisticated understanding of what it takes to deliver novel therapies to patients and a willingness to dive in and participate in this process. I am looking forward to being a part of this dynamic and passionate team.”
The thought leadership of Dr. Cara O’Neill, Chief Science Officer at Cure Sanfilippo Foundation, a pediatrician, and mother to a daughter with the rare disease Sanfilippo Syndrome (MPS III), in the rare disease space is being recognized at an international level.
Each year, WORLDSymposium recognizes one individual for their patient advocacy leadership in the field of lysosomal disease. Dr. O’Neill is the recipient of the 2020 Patient Advocate Leader Award, which will be presented WORLDSymposium 2020 on Feb. 12, 2020.
The award, which began in 2016, recognizes an individual for their direct contribution to lives of patients and families dealing with a lysosomal disease through disease awareness and education, community mobilization, non-profit development and/or good governance activities, patient care, and support programs. Past recipients include remarkable leaders such as Barbara Wedehase, former Executive Director of the MPS Society (2016); Christine Lavery, Group Chief Executive for the UK Society for Mucopolysaccharide Diseases (2017); Jack Johnson, Executive Director of the Fabry Support & Information Group (2018), and Mark Dant, Chairman of the EveryLife Foundation for Rare Diseases and founder of The Ryan Foundation (2019).
“It is a great honor to receive this award, and I am humbled to be among past recipients of such high caliber and contribution,” said Dr. O’Neill. “Cure Sanfilippo Foundation has found many great partners interested in collaborating with us on new clinical strategies, improved patient input, and pathways for faster diagnosis, which benefits all families dealing with Sanfilippo Syndrome, as well as patient communities in other diseases.”
Dr. O’Neill’s uniquely-paired career and life experiences allow her to bridge gaps between scientists, clinicians, industry, and families, helping foster patient-centered research and future translational paths for rare disease treatments.
She leads patient-focused research efforts within Cure Sanfilippo and has presented at international conferences and authored peer-reviewed journal articles. In addition, she collaborates with other non-profit groups on mutual advocacy and research interests, as well as oversees the Foundation’s funding of external scientific programs.
Dr. O’Neill leads in developing innovative integration of patient perspective and technology into study design and pioneering support for pediatricians in diagnosing rare diseases early, such as:
- Conducting the first-ever Sanfilippo Caregiver Preference Study;
- Piloting The GAPP Project, using cutting-edge facial recognition technology in pediatric clinics to accelerate accurate diagnosis and access to specialized geneticist for a wide range of genetic conditions;
- Collaborating with Sanfilippo Children’s Foundation (Australia) to create Global Clinical Management Guidelines for Sanfilippo, a crucial clinician tool as there is only scarce, fragmented management guidance currently available; and
- Leveraging technology, such as wearable devices and video capture of disease symptoms (gait, motor skills, speech, social interaction), to improve the quantity and quality of date used to evaluate experimental therapies.
“Her work has broader application than just Sanfilippo Syndrome. Many of the clinical and scientific strategies that O’Neill leads could be applied to multiple diseases, even beyond rare diseases, making her contributions to the scientific community exceptional,” said Dan Fraley, Chair of Cure Sanfilippo Foundation.
“This is fantastic news and a well-deserved honor for Dr. O’Neill. It has been a true inspiration to work with her on initiatives to improve the lives of patients with Sanfilippo Syndrome and their families,” said Wayne Pan, MD PhD MBA, Medical Director/Global Medical Affairs for BioMarin. “It is wonderful to see the lysosomal storage disease community recognizing her for all of your contributions.”
Created in 2014 by O’Neill and her husband Glenn, Cure Sanfilippo Foundation has already raised more than $8 million through grassroots and viral fundraising which has helped fund more than 20 research projects, including the first-ever gene therapy clinical trials for Sanfilippo Syndrome. A complete list of funded projects can be viewed at CureSFF.org/Grants.
Picking outcome measures for neurodegenerative gene therapy trials in rare disease is difficult. The conditions often have a lot of heterogeneity, relatively small sample sizes, and rarely disease-specific outcome measures. That is why “outside the box” thinking is necessary, and Cure Sanfilippo Foundation Chief Science Officer Cara O’Neill, MD FAAP, shared how novel outcomes could be used to expand and improve evaluation of gene therapy trials for neurodegenerative diseases at the Lysogene/Sarepta satellite symposium during SSIEM 2019 last week in Rotterdam, Netherlands.
Most of the measures used in childhood neurodegenerative conditions are drawn from more general measures based on normal neurodevelopment and behavior patterns, rather than hallmarks of particular disease. So rare diseases are always being compared to “Normal.” But is that a fair comparison knowing that these patients have had chronic ongoing brain injury to the immature developing brain?
“We have to do a better job of matching endpoints with the patient’s needs across the spectrum of any given disease,” urged O’Neill.
The key is meeting the patient needs, not the clinician’s needs or fulfilling assumptions that have been made in the past about patients’ need.
“We must get as close as we can to discerning what is going to make their life better, for however long that is.”
Sharing early data from the Foundation’s MPS III Caregiver Preference Study, O’Neill noted that the more than 160 Sanfilippo caregivers across 14 different countries listed pain, communication, mobility and hyperactivity among their treatment priorities. Additionally, what caregivers prioritize changes along the course of the disease.
O’Neill detailed how the Foundation has partnered with Aparito, Casimir Trials, and Lysogene to conduct an exploratory study of novel outcomes for MPS IIIA running in parallel to AAV10-SGSH intracranial gene therapy trial. The study uses frequent video capture by caregivers to monitors specific disease hallmarks and priorities identified by the Caregiver Preference Study in the child’s familiar environment to capture the child’s best ability.
The patient-reported outcome videos study has allowed detection of subtle, but meaningful, incremental changes and appears feasible for longer term monitoring of real-world functioning and patient status, reported O’Neill.