PMSF announced a research grants program in January 2023 to provide funding to highly motivated scientists studying Phelan-McDermid syndrome. Our goal is to accelerate exciting clinical research which aligns with community interests. Scientists from around the world sent in applications for three main grant categories. The number and quality of submissions surpassed expectations, making it hard to select only one winner in each category. Each grant was reviewed by scientific advisors and invested family members to determine winners – thank you to all reviewers! Winners will be supported financially for a year of research. We are thrilled to announce the winning projects below. Thank you to our generous donors who make this work possible.

2023 Neuropsychiatric Illness and Regression Fellowship 

AWARD DESCRIPTION: A subset of people with Phelan-McDermid syndrome (PMS) experience devastating psychiatric symptoms, such as regression, bipolar disorder, and catatonia. The goal of this fellowship is to better understand these psychiatric symptoms, refine medical guidelines, and/or explore the underlying reasons for these symptoms. This award is a partnership with the NIH-funded Natural History Study team. Resources from the Natural History Study will be used to strengthen the research.

AWARD WINNER:  “Investigating Immune and Autoimmune Mechanisms of Neuropsychiatric Decompensation in Phelan-McDermid syndrome”

• Milena Andzelm, MD, Ph.D., Boston Children’s Hospital – Principal Investigator (PI) – primarily responsible
• Siddharth Srivastava, MD, Boston Children’s Hospital – Mentor – helps guide the PI
• Tesi Kohlenberg, MD – consultant – provides expertise

PROJECT SUMMARY: A subset of individuals with PMS develop serious neuropsychiatric illness (SNPI) in their teens or twenties, and about half with SNPI have new lasting loss of skills (regression). PMS patients with SNPI are hard to treat with psychiatric medications, and some have responded to treatments that target the immune system. This fact, combined with the knowledge that SHANK3 is present in an organ of the immune system (the thymus) has led to interest in understanding whether people with PMS –particularly those with SNPI — have underlying differences in their immune system that might guide treatment.

This study will explore these questions as follows:

1. Families whose children are over age 10 will fill out three online questionnaires, one on psychiatric symptoms, one on loss of skills, and one on family history of autoimmune disease. These will be scored to determine which have SNPI.
2. Participants will be invited to have their child’s blood drawn for immune studies and to consent to a review of their child’s medical records to examine studies already done. This will allow us to compare those with and without SNPI.
3. Families whose children have lumbar punctures as part of their current medical care will be asked to donate a sample of the spinal fluid for state of the art studies of brain inflammation.

Results of standard lab tests will be shared with participants’ doctors, and the analysis of the study measures will provide rich information on the role of the immune system.

 2023 PMSF Innovation Award

AWARD DESCRIPTION: For applications which explore an understudied area of Phelan-McDermid syndrome (PMS) research. Successful proposals will open new avenues of research in the field. Applications with clinical relevance were preferred.

AWARD WINNER: “Precision treatment for Phelan-McDermid syndrome – A novel pre-clinical approach”

• Bridgette Moffitt, Ph.D., Clemson University – Principal Investigator (PI) – primarily responsible
• Luigi Boccuto, MD, Clemson University – Mentor – helps guide the PI
• Sara Sarasua, Ph.D., Clemson University – Co-Investigator (Co-I) – provides value to the application but does not take on responsibility for the research

PROJECT SUMMARY: Phelan-McDermid Syndrome (PMS) is characterized by intellectual disability, autistic features, developmental delays, and neonatal hypotonia. The way signs and symptoms present may change extensively from one person with PMS to another. This makes designing treatment approaches very difficult. Several clinical trials have used Insulin-like Growth Factor 1 (IGF-1) and human growth hormone (hGH) to improve the neurological symptoms in PMS. We wanted to see how IGF-1 and hGH could help people with PMS, so we looked at the way cells from individuals with PMS change their metabolism when exposed to these compounds. Our goal was to identify individuals who would benefit more from the treatment. Based on their different responses to IGF-1 and hGH, we placed people with PMS into distinct subgroups. The purpose of this study is to apply the same approach to other compounds used for clinical trials in PMS. Our study aims to (1) study the response of cells from individuals with PMS to candidate treatments and (2) identify subgroups in the PMS population that will potentially respond better or worse to the selected compounds. The classification of individuals with PMS into subgroups based on responses to candidate treatments meets several objectives. It allows for future investigations into possible causes of differences in the presentation of PMS features, explores the response to candidate drugs at the cellular level, and potentially offers a better selection of the people who could benefit the most from clinical trials, reducing their risk of adverse effects.

 2023 PMSF Translational Research Award

AWARD DESCRIPTION: For applications that have promising data and are looking to make clinical impact in a short period of time. This could include the development of new therapeutics or new clinical assessments for Phelan-McDermid syndrome (PMS). 

AWARD WINNER: “Validation of a Novel, Inexpensive, Home-Based Gastrointestinal Transit Test among People with Phelan-McDermid Syndrome”

• Julia Dallman, Ph.D., University of Miami – Principal Investigator (PI) – primarily responsible
• Calliope Holingue, Ph.D., Kennedy Krieger Institute – Co-PI – shares equal responsibility with PI
• Baharak Moshiree, MD, Atrium Health – Co-PI – shares equal responsibility with PI
• William Bennett, MD, Indiana University – Co-PI – shares equal responsibility with PI
• Barbara Millet, Ph.D., University of Miami – Co-Investigator (Co-I) – provides value to the project but is not primarily responsible for the project

PROJECT SUMMARY: Gastrointestinal (GI) symptoms are common and negatively impact the quality of life among people with Phelan-McDermid syndrome (PMS). These symptoms include constipation, which may be related to altered movement of the gut called motility. Current GI motility tests are difficult to do in people with PMS. We have developed an alternative objective measure of GI transit: muffins with blue dye and a mobile app that allow caregivers to track GI transit time at home. Pilot data show this test works as intended; individuals eat the muffins and transit times are captured by observing the blue color in poop. The goal of this proposal is to improve this inexpensive GI transit test for larger studies. In Aim 1a, we will work with PMS caregivers to make the mobile app easier to use. In Aim 1b, we will conduct the blue dye test among up to 75 people with PMS. We will also collect a detailed history of constipation and other GI symptoms, genetic diagnoses, and previous GI testing to assess whether the blue dye test is measuring what it’s supposed to measure. In Aim 1c, participants will complete the blue dye test a second time (14-30 days later) to test how transit time changes over time. Participants with feeding tubes (30/75) will do a modified version of the test by mixing blue dye into their standard feeding formula. This remote-based study would provide families with an objective measure of GI transit that they can do at home to help manage symptoms.

                               The PMSF will update the community as these research projects progress!