Geraldine Bliss, Co-Founder and President of CureSHANK, and Jenny Graham Beeson, Board Member for CureSHANK, discuss clinical research in Phelan-McDermid syndrome (PMS) and the Start Genetic initiative.
PMS is a chromosome disorder caused by deletions at 22q13.3. The loss or the variation of the SHANK3 gene is likely responsible for many of the common features associated with PMS. Common symptoms include hypotonia, intellectual disability, developmental delays, and epilepsy. Differences in physical features may include long eyelashes, down slanting eyes, large ears, ears without normal folding, bulb-like tip of nose, pointed chin, large hands, and toenails that flake off as infants and then become hard and brittle as age. Unusual behaviors may include mouthing or chewing on non-food items, decreased perception of pain, and autistic-like behaviors such as flapping of hands and repetitive motions.
CureSHANK is a non-profit organization focused on finding a cure for PMS. It is currently involved in a variety of research studies focused on the development of novel therapies for PMS and getting them into clinical trials. Through collaboration with Neuren, the first patient was dosed in February 2026 in a phase 3 clinical trial of IGF-1 analog, NNZ-2591. As Ms. Bliss highlights, this marks the organization’s first phase 3 trial for PMS, helping to establish regulatory pathways for future treatments. Additionally, Jaguar Gene Therapy’s SHANK3 minigene replacement therapy has been officially dosed in five patients with no serious adverse events related to the therapy and early signs of improvement. The next step is a dose escalation study (NCT06662188).
CureSHANK is also working to facilitate natural history studies and the development of new biomarkers. Ms. Bliss explains this area of unmet need is caused by the diverse behavioral phenotypes of PMS that pose challenges in establishing outcome measures due to their subjectivity of improvement.
Genetic testing is also an area of focus for the organization, with their board members coming together to form Start Genetic. This initiative spreads awareness of genetic testing for a variety of genetic disorders through a Genetic Testing Action Day of July 25.
To learn more about PMS and other rare genetic disorders, visit https://checkrare.com/diseases/congenital-and-genetic-conditions/