Phelan-McDermid Syndrome (PMS)
Phelan-McDermid syndrome (PMS) is a rare genetic condition often linked with an intellectual disability, language delays, autism spectrum disorder. At Protheragen, we are committed to creating novel therapeutics as well as precise animal models that will expedite preclinical PMS studies. With our experience, we completely guarantee that clients research receives the best tailored and dependable assistance, fast tracking their drug development journey.
Overview of Phelan-McDermid Syndrome (PMS)
Phelan-McDermid syndrome (PMS), or 22q13 deletion syndrome, is a rare neurodevelopmental disorder resulting from haploinsufficiency of the SHANK3 gene due to deletions or pathogenic changes in the ends of chromosome 22 (22q13.3). This syndrome has an estimated prevalence of 1 in 15,000 to 20,000 births, although the true incidence may be higher due to underdiagnosis.
Fig.1 Clinical relevance of molecular studies and brain organoids from patients with Phelan-McDermid syndrome (PMS). (Sakai Y, et al., 2022)
Pathogenesis of Phelan-McDermid Syndrome (PMS)
Phelan-McDermid syndrome (PMS) arises due to SHANK3 haploinsufficiency resulting from 22q13.3 deletions or mutations. SHANK3 deficiency as a scaffolding protein at the postsynaptic density disrupts glutamatergic signaling by NMDA/AMPA receptors and dendritic spines, which alters their maturation and structure. Increased neuronal hyperexcitability alongside abnormal synaptic plasticity and disturbances in the balance between excitation and inhibition leads to core neurodevelopmental deficits: autism-like behaviors, intellectual disability, and motor skill impairments.
Fig.2 SH3 and multiple ankyrin repeat domains 3 (SHANK3) protein domains. (Costales J L, Kolevzon A., 2015)
Therapeutic Development for Phelan-McDermid Syndrome (PMS)
| Therapy | Mechanism of Action | Targets | NCT Number | Research Phase |
| RB001 Gene Therapy | AAV-mediated delivery of functional SHANK3 gene to restore synaptic scaffolding. | SHANK3 protein | NCT07014020 | Phase I/II |
| Recombinant Human Growth Hormone Therapy | Stimulates IGF-1 production, promoting neuronal growth and synaptic plasticity. | IGF-1 receptor | NCT05105685 | Phase II |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Specializing in comprehensive solutions for Phelan-McDermid syndrome (PMS), Protheragen integrates diagnostic development with cutting-edge in vitro diagnostic (IVD) kits for early disease identification. Our therapeutic development pipeline leverages exclusive disease models, such as physiologically representative blood-brain barrier (BBB) models, to expedite the exploration and authentication of central nervous system (CNS) targeted treatments.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- SHANK3 Knockout Model: The model uses genetic engineering techniques to completely or conditionally knock out the SHANK3 gene to reproduce the synaptic dysfunction and neurobehavioral defects observed in Phelan-McDermid syndrome (PMS)
- Other Models
To advance the commercialization of novel therapies for Phelan-McDermid syndrome (PMS), Protheragen provides comprehensive preclinical research services, covering pharmacodynamics (PD), pharmacokinetics (PK), and toxicology studies. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Sakai Y, Okuzono S, Schaaf C P, et al. Translational pediatrics: clinical perspective for Phelan–McDermid syndrome and autism research[J]. Pediatric Research, 2022, 92(2): 373-377.
- Costales J L, Kolevzon A. Phelan–McDermid syndrome and SHANK3: Implications for treatment[J]. Neurotherapeutics, 2015, 12(3): 620-630.