Prader-Willi Syndrome (PWS)
Prader-Willi syndrome (PWS) is a complex neurogenetic disorder caused by loss of paternally expressed genes in the 15q11-q13 chromosomal region. Leveraging our pioneering efforts in PWS research, Protheragen is at the forefront of developing cutting-edge therapies to enhance the effective management of PWS. As your trusted partner in PWS drug development research, we provide unparalleled support to meet your research needs.
Overview of Prader-Willi Syndrome (PWS)
Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder caused by deletions of paternally expressed genes in the 15q11-q13 chromosomal region that affects approximately 1 in 10,000 to 30,000 live births. The syndrome has a biphasic clinical course: severe hypotonia and feeding difficulties in the neonatal period, followed by obesity, developmental delay, and endocrine dysfunction caused by binge eating in childhood.
Fig. 1 Gut microbiota and Prader-Willi syndrome (PWS). (Ramon-Krauel M, et al., 2021)
Pathogenesis of Prader-Willi Syndrome (PWS)
The origin of Prader-Willi syndrome (PWS) is due to genomic imprinting anomalies on chromosome 15q11-q13 with loss of paternally expressed genes SNORD116, MAGEL2, and NDN causing disruption of hypothalamic function. Loss of SNORD116 causes development of oxytocin neurons to be impaired and satiety signaling to inefficiently function which drives hyperphagia. In addition, MAGEL2 loss also impacts circadian rhythm and neuroendocrine regulation. In concert with growth hormone deficiency, elevated ghrelin leads to worsening of metabolic abnormalities.
Fig. 2 Mechanisms involved in the development of obesity in Prader-Willi syndrome (PWS). (Muscogiuri G, et al., 2021)
Therapeutic Development for Prader-Willi Syndrome (PWS)
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Diazoxide Choline | Activates ATP-sensitive potassium channels to suppress insulin release and modulate appetite-regulating neurons in the hypothalamus. | KATP channels, hypothalamic neurons | Approved |
| Somatropin | Recombinant human growth hormone (rhGH); stimulates growth, improves metabolism, and increases lean body mass. | Growth hormone receptor (GHR) | Approved |
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
At Protheragen, we focus on preclinical research in Prader-Willi syndrome (PWS), providing comprehensive solutions from biomarker identification to development of CNS targeted therapeutics. Our expertise covers disease modeling, including patient-derived iPSCs, genetically engineered models, and advanced blood-brain barrier (BBB) models for evaluating drug penetration and neuroprotective efficacy. We provide partners with target validation, lead compound optimization, and comprehensive preclinical research services.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
- Snord116 Knockout Model
- Magel2 Knockout Model
- EHMT2/G9a Conditional Knockout Model
- Necdin Conditional Knockout Model
- Other Models
At Protheragen, we offer comprehensive pharmacodynamic (PD), pharmacokinetic (PK), and toxicology research services to support the development and regulatory approval of potential therapies for Prader-Willi syndrome (PWS).If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Ramon-Krauel M, Amat-Bou M, Serrano M, et al. Targeting the gut microbiome in Prader-Willi syndrome[J]. Journal of Clinical Medicine, 2021, 10(22): 5328.
- Muscogiuri G, Barrea L, Faggiano F, et al. Obesity in Prader–Willi syndrome: Physiopathological mechanisms, nutritional and pharmacological approaches[J]. Journal of Endocrinological Investigation, 2021, 44(10): 2057-2070.