The Phelan-McDermid Podcast: Sharing Research, Progress, and Hope

How do we measure meaningful progress in individuals with Phelan-McDermid syndrome, especially when traditional developmental assessments often miss important milestones? How do we capture meaningful change in clinical trials, especially when traditional measures are not sensitive enough to things that actually matter to our families? To help answer these questions, Dr. Lauren welcomes Dr. Natasha Ludwig from Kennedy Krieger Institute and Dr. Mary Wojnaroski from Nationwide Children’s Hospital to discuss the Inchstone Project and its latest project, Parents Speak Survey 2 (PSS2).Learn how this innovative research is working to develop more inclusive outcome measures that capture meaningful changes in cognition, communication, behavior, and development across rare neurogenetic conditions, including Phelan-McDermid syndrome. Our guests discuss the importance of caregiver perspectives, collaboration with the FDA, and how better assessments can improve clinical trial readiness.We also explore how families can participate in PSS2, a remote, study open to individuals ages one and older with Phelan-McDermid syndrome! Learn more and participate: https://inchstoneproject.org/pss2/

What is the PMS DataHub? And why does participation matter?In this episode of the Phelan-McDermid Syndrome Podcast, Dr. Lauren is joined by Kathy Fiscus, PMSF Data Manager and co-principal investigator of the PMS DataHub, to explain how this important resource supports both families and Phelan-McDermid syndrome research.Kathy breaks down the difference between the current PMS DataHub and the legacy Phelan-McDermid Syndrome International Registry (PMSIR), explains how genetic reports are curated, and shares how researchers can use registry information to identify potential participants for studies.Families also will learn about tools available within the DataHub, including de-identified survey results, document storage and sharing, medication and symptom tracking, and a personal journal. The conversation also explains why keeping health information current and uploading a genetic report can be valuable as new research opportunities emerge.Dr. Lauren ends the episode reminding families of children aged 1-17 years to upload their genetic reports if they are interested in joining the next phase of the Observer-Reported Communication Ability (ORCA) study. ORCA will exclusively be recruiting families who have curated genetic reports in the PMS DataHub. Tune in to future episode to learn even more about what the ORCA team has accomplished so far and about their new study! Learn more at pmsf.org/DataHub or contact [email protected] for assistance.Needing additional help? You can schedule DataHub Help Desk with Kathy here!

In this episode of the Phelan-McDermid Syndrome Podcast: Sharing Research, Progress, and Hope, Lauren is joined by Dan Gallo, Executive Vice President and Head of Clinical Development and Medical Affairs at Jaguar Gene Therapy, and Tessa Clarkson, Clinical Development Consultant at Jaguar Gene Therapy.They discuss Jaguar’s Developmental Milestone Survey, a study designed to better understand how people with Phelan-McDermid syndrome gain, lose, and potentially regain meaningful developmental skills. The goal is to identify developmental patterns that could help researchers measure meaningful treatment effects and inform future clinical trials—including potentially reducing the need for placebo-controlled designs.The conversation covers the survey’s scientific rationale, lessons from a similar approach in Rett syndrome, eligibility and participation, and why family participation is especially important as Jaguar prepares for discussions with the FDA about future JAG201 development.JAG201 update: As of August 21, 2026, Jaguar reported that Cohort 1 dosing in its Phase 1/2 trial was complete and Cohort 2 dose escalation was underway. Jaguar described early indications of clinical benefit across neurodevelopmental domains and an emerging safety profile with no treatment-related serious adverse events reported to date, while emphasizing that more follow-up and complete analysis are needed before conclusions can be drawn.Learn more about the Developmental Milestone Survey: pmscaregiverstudy.com

In this episode of the Phelan-McDermid Syndrome Podcast: Sharing Research, Progress, and Hope, Dr. Lauren talks with Dr. Michael Long of NYU Langone, a neuroscientist studying the brain circuits that make vocal communication possible.This episode is a fascinating look at an unconventional approach to one of the Phelan-McDermid syndrome community's highest research priorities: communication and language.Dr. Long shares how his research has taken him from songbirds and human speech to an unusual animal with remarkable conversational abilities: the singing mouse. Unlike standard laboratory mice, singing mice engage in precisely timed, back-and-forth vocal exchanges, much like humans! After collaborating with Dr. Ben Scott (featured on "A Cross-Species Approach to Advancing Research in Phelan-McDermid Syndrome with Dr. Ben Scott and Amanda Fath"), Dr. Long has been working to develop a SHANK3 knockdown singing mouse. This will allow researchers to better understand the underlying brain circuitry involved in communication and how disruption to SHANK3 alters this.The conversation also explores why communication encompasses much more than spoken words, the importance of including minimally verbal and non-speaking individuals in research, and how "backward translation" (taking observations from individuals with Phelan-McDermid syndrome back into the laboratory) can help scientists ask better questions and develop more meaningful models.If you are interested in being involved with Drs. Scott and Long's study, check out the GEODE (Gathering Evidence for Optimizing Decisions) Study on our Open Studies page or contact: [email protected].

What do PMSF's relationships with pharmaceutical companies and other industry companies really mean for families?In this episode, Dr. Lauren Schmitt, Chief Science Officer, and Amanda Bergen, Director of Communications, take you behind the scenes to discuss how PMSF builds meaningful relationships with industry while keeping the voices of individuals with Phelan-McDermid syndrome and their families at the center.They explore how family feedback helps shape clinical trial design, educational resources, and research priorities, while also explaining what PMSF's role is AND what it is not. You'll also hear how these relationships can support PMSF's mission, why transparency matters, and how your participation in the registry, surveys, and community conversations helps move research forward.Whether you're new to the Phelan-McDermid syndrome community or have been following research for years, this episode offers an inside look at how collaboration can help advance better treatments while staying true to PMSF's mission of CONNECT, CARE, and CURE.Learn more about ongoing clinical trials at clinicaltrials.gov or on our webpage at www.pmsf.org/clinical-trials.

Sensitive Content Notice: This episode discusses brain donation and postmortem tissue research. Our goal at PMSF is to provide clear, transparent information so families can better understand all areas of research. While we approach this sensitive topic with care and compassion, we recognize this episode may not be suitable for everyone. In this episode, Dr. Lauren speaks with Dr. Alyicia Halladay (Chief Science Officer at the Autism Science Foundation) and Lilliam Acosta (Outreach Manager at Autism BrainNet) about Autism BrainNet, a program funded by the Simons Foundation that supports autism research through the gift of brain donation. Together, they address common questions and misconceptions and discuss how postmortem brain tissue can help advance research in Phelan-McDermid syndrome.To learn more about Autism BrainNet: https://www.autismbrainnet.org/You can also sign up for the Autism BrainNet newsletter here:https://www.autismbrainnet.org/newsletter/💚 We also recognize that conversations about loss can bring up difficult emotions. PMSF offers a monthly support group for bereaved Phelan-McDermid syndrome parents. You can learn more about this support program here: https://pmsf.org/caregiver-support-groups/

In this episode, Dr. Lauren meets with the 2026 PMSF Family Conference co-chairs and PMSF staff, Amanda Bergen (Director of Communications) and Carla D'Imperio (Director of Family Support).Taking place July 15–19, 2026 in Aurora, Colorado at the Gaylord Resort, this year’s conference is centered around the theme “The Climb We Make Together”, highlighting the shared journey of families, clinicians, researchers, and advocates working to improve the lives of individuals with Phelan-McDermid syndrome.We discuss:What to expect from this year’s conference programmingThe three core pillars: Connect (Basecamp), Care (Ascent), and Cure (Summit)New structure of "Deep Dive" sessions on GI issues, loss of skills/regression, and neuropsychiatric illnessConnection to Pathways, like pre-conference family focus groups and post-conference follow-upExpanded support for families, including travel assistance, sibling programming, and one-on-one expert consultationsWhy attending in person can be such a meaningful and transformative experienceWith nearly 700 attendees expected, this conference offers a unique opportunity to connect, learn, and make the climb—together.Learn more about the conference and direct links to register here: https://pmsf.org/2026-conference/ You can also reach out directly at [email protected]

In this episode of the Phelan-McDermid Syndrome Podcast: Sharing Research, Progress, and Hope, we explore an innovative approach to translational neuroscience: cross-species research.Dr. Lauren is joined by Dr. Benjamin Scott (Boston University) and Amanda Fath (MIT, Guoping Feng Lab) to discuss how researchers are using a shared, game-based task across humans, mice, and non-human primates to better understand how brain circuits influence perception, learning, and decision-making in Phelan-McDermid syndrome . Their short, engaging computer-based game (“Asteroids”) is more accessible to individuals with Phelan-McDermid syndrome. And the researchers remind us why "All data is good data".This work aims to bridge a long-standing gap between animal models and human experience through computational models that connect behavior to underlying brain circuits. Ultimately, this work is aimed at improving how discoveries translate into meaningful treatments.Research Participation Opportunity!The research team is currently recruiting individuals with Phelan-McDermid syndrome:Eligibility: 11–21 years old diagnosed with Phelan-McDermid syndrome; Able to use a touchscreen device or mouse; Do not have a seizure disorder or history of seizures that could be triggered by flashesFormat: Fully virtual Time commitment: 20-40 minutesIf you’re unsure whether your loved one can participate—reach out. Even partial participation provides valuable data.If interested in enrolling, or for more information, contact: [email protected] or 203-216-9618

This episode's guest:Dr. Jonathan Santoro, MDPediatric Neurologist & NeuroimmunologistChildren’s Hospital Los Angeles (CHLA)2025 Shannon O’Boyle Memorial Neuropsychiatric Illness Grant AwardeeOverview:In this episode, we welcome Dr. Jonathan Santoro, our 2025 Shannon O’Boyle Memorial Neuropsychiatric Illness Grant Awardee, who is pediatric neurologist. Dr. Santoro's work focuses on developmental regression and neuropsychiatric illness, and he shares with Dr. Lauren why his research team is turning its attention to Phelan-McDermid syndrome (PMS).Dr. Santoro’s PMSF-funded project, “Diagnostic Biomarkers in Phelan-McDermid Syndrome-Associated Neuropsychiatric Disease,” uses tests that are already part of standard clinical care (like EEGs, MRIs, blood work, and lumbar punctures), the team will look for biological “signatures”, or biomarkers, to help lead to better diagnosis, earlier detection, and more targeted treatments for individuals with Phelan-McDermid syndrome who experience neuropsychiatric illness.His study is currently enrolling (February 2026)Check out our open studies page for more information: https://pmsf.org/current-open-research/

In this episode, we welcome Dr. Natasha Ludwig (Kennedy Krieger Institute / Johns Hopkins) and Dr. Jenny Downs (Kids Research Institute, Australia) for an exciting update on the Inchstone Project—a collaborative international effort to improve how we measure progress and quality of life for individuals with developmental and epileptic encephalopathies (DEEs), including Phelan-McDermid Syndrome (PMS).We discuss:What the Inchstone Project is and why it mattersHow families helped shape new research by contributing to the DEE Parent Speak SurveyKey findings on quality of life, including the importance of communication, cognitive skills, and touchscreen useWhat “clinical meaningfulness” really means—and why small changes can have a big impactHow this research is informing clinical trial readiness and future interventionsWhat’s next for the Inchstone team, including a follow-up longitudinal studyPMS families made up nearly 20% of the study sample! Thank you for helping move science forward.Recorded: July 22, 2025Aired: January 21, 2026Updates since being recordedDr. Ludwig is a confirmed speaker at the 2026 PMSF Family Conference!The paper on quality of life is published! Check it out here: https://link.springer.com/article/10.1007/s11136-025-04153-0