Researchers Panel Discussion and Audience Q&A

Quick Overview

The panel discussion at the 2022 FAST Science Summit addressed various questions from the audience, covering topics such as genetic testing, overexpression of UBE3A, snoRNAs, clinical trials, caregiver impact, and newborn screening. Researchers provided insights into the challenges and potential solutions for these issues. Key takeaways include the importance of caregiver-reported measures in clinical trials, the need for rigorous evidence to support the inclusion of conditions in newborn screening panels, and the potential of new technologies like CRISPR RNP for gene editing. Overall, the researchers expressed optimism for the future of Angelman syndrome research and emphasized the importance of continued collaboration and support from the community.

The 2022 FAST Science Summit featured a panel discussion with researchers and an audience Q&A session. The panelists addressed questions from the audience, as well as questions that were submitted online via social media during the Thanksgiving weekend. The panelists aimed to provide insights and information about various topics related to Angelman syndrome research and treatment.

Addressing Audience Questions

The panel moderator began by explaining that questions were collected online to give families time to think about the topics and submit their questions privately. The moderator acknowledged that some families may feel uncomfortable asking questions in person and assured them that their questions would be addressed. The moderator then randomly selected questions for each panelist.

Concerns about UBE3A Overexpression and Paternal Activation

One of the questions was directed at Dr. Dindot and Dr. Keung regarding concerns about overexpression of UBE3A in paternal activation for the UPD and ICD genotype. The question asked about the potential risks and benefits of paternal activation compared to maternal replacement of UBE3A. Dr. Dindot explained that there is evidence that overexpression of UBE3A can be associated with cognitive deficits. However, the dosage of UBE3A can be controlled with antisense oligonucleotides (ASOs), which may require a lower dose. Dr. Keung added that the function and impact of snoRNAs downstream of UBE3A are still not fully understood, but there is no known problem with having too much snoRNAs.

Maternal Replacement Option and Genotypic Considerations

The panelists discussed the potential benefits and considerations of a maternal replacement option for UPD and ICD genotypes. Dr. Jiang emphasized the need for more knowledge and understanding of the effects of different treatments on these genotypes. He mentioned the importance of studying the developmental timing of genes and the potential impact of reducing snoRNAs. Dr. Jarvis added that the choice between paternal activation and maternal replacement would depend on the specific drug program and the mechanism of action of the drug.

Primary Endpoint and Caregiver Reported Measures

The panelists addressed a question about the use of caregiver-reported measures, such as the ORCA (Outcome Measures in Rheumatology Clinical Trials) scale, as a primary endpoint in Angelman syndrome clinical trials. Dr. Zigler explained that the selection of a primary endpoint depends on various factors, including the mechanism of action of the drug and the data supporting the measure. He emphasized the importance of considering both caregiver-reported and clinician-reported data to get a comprehensive understanding of the treatment’s effects.

Long-Term Access to Drugs after Clinical Trials

The panelists discussed the issue of long-term access to drugs after clinical trials. The question asked whether patients would need to pay for the drug or if the company running the trial would provide it. Dr. Pitluck explained that after regulatory approval, pharmaceutical companies would work with insurance companies to secure payment for the drug. The goal is to ensure that patients have access to the drug without having to pay out-of-pocket. The panelists highlighted the importance of advocating for reimbursement and ensuring that payers are ready to cover the costs.

Newborn Screening and Prevalence

The panelists addressed questions about newborn screening and its impact on understanding the prevalence of Angelman syndrome. Dr. Kucera explained that newborn screening panels already include various conditions, and the process of adding new conditions is slow and requires extensive evidence. She mentioned the potential of sequencing-based studies for rare conditions but acknowledged the need for a major change in newborn screening. Dr. Baker added that newborn screening costs depend on various factors, including the testing itself and the follow-up required.

Bio-Distribution of CRISPR RNP Technology

Dr. Daniel discussed the bio-distribution of CRISPR RNP technology and its potential in treating Angelman syndrome. He explained that the technology has shown high efficiency in cell cultures and mouse models. However, the bio-distribution in larger brains, such as non-human primates and humans, is still unknown and requires further study.

Optimism for the Future

In conclusion, the panelists expressed their optimism for the future of Angelman syndrome research and treatment. They acknowledged the progress made by the community and the unique opportunities for therapeutic development. They emphasized the need for continued collaboration, innovation, and advocacy to accelerate progress and improve the lives of individuals with Angelman syndrome.

The panel discussion and audience Q&A provided valuable insights and addressed important questions from the Angelman syndrome community. The researchers and experts demonstrated their dedication and commitment to advancing knowledge and finding effective treatments for Angelman syndrome.

Talk details

  • Title: Researchers Panel Discussion and Audience Q&A
  • Author(s): None
  • Author(s)’ affiliation: None
  • Publication date: 2022-12-15
  • Collection: 2022 FAST Science Summit