Juvenile Polyposis Syndrome (JPS)
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Juvenile polyposis syndrome (JPS) is a rare genetic condition with autosomal dominant inheritance that is typified by several juvenile polyps in the gastrointestinal tract and is often linked to mutations in SMAD4 and BMPR1A. Protheragen has distinguished itself as a premier service provider of drug development research for rare gastrointestinal syndromes like JPS by offering useful services and support for research and therapy development.
The condition known as JPS is typified by a predisposition to hamartomatous polyps in the gastrointestinal tract which include stomach, small intestine, colon, and rectum. The estimated number of cases occurring is from 1 in 100,000 to 1.6 in 160,000. The term "juvenile" does not refer to the age of presentation of the polyps but the type of the polyp found. Therapy is essential, as polyps left unchecked can result in anemia and bleeding. The chance of having gastrointestinal cancer is between 11% to 86%.
Subtypes of JPS include JPS of infancy, generalized JPS, and juvenile polyposis coli.
Fig.1 The TGF-β pathway involves BMPR1a signaling via SMAD4. (Papadopulos, M. E., et al., 2023)
JPS genetic basis entails germline mutations either in BMPR1A or SMAD4. The bone morphogenetic protein receptor 1A (BMPRIA) is a serine-threonine kinase type I receptor that participates in the signaling of the transforming growth factor-β (TGF-β) superfamily. After receptor activation, the receptor phosphorylates and activates the cytoplasmic SMAD proteins. Both genes control, directly or indirectly, the cell's growth inhibition and apoptosis.
Fig.2 Mutation analysis of individual with JPS. (Gao, X. H., et al., 2020)
Up until now, JPS was managed with surgical interventions alongside endoscopic surveillance. A shift to new strategies is now emerging that focus on minimizing the polyp load and inhibiting or averting neoplastic development through molecular therapies.
COX-2 as a Therapeutic Target
These adenomatous polyps seem to dramatically overexpression COX-2, which indicates that inflammation may be an underlying factor in the growth of polyps for JPS individuals. Celecoxib and meloxicam, are the most studied COX-2 inhibitors in polyposis conditions. They have been reported to effectively diminish the number and size of colorectal polyps.
mTOR as a Therapeutic Target
In JPS, unexplained activation of the mTOR pathway is likely responsible for the unregulated growth of polyps and thus serves as a potential target for therapeutic. Several studies targeting JPS have utilized mTOR inhibitors such as sirolimus (rapamycin) to decrease the creation of gastrointestinal polyps and prolong the dysplastic progression in individuals.
Taking advantage of new technologies and practices to guarantee maximum accuracy for the data and insights, our skilled team strives to further the understanding and course of therapy for JPS and related conditions. We provide a full range of services, including basic and preclinical research as well as trial management and regulatory support which encompasses the development of diagnostics, therapeutics, and disease models.
Animal models are critical in studying the pathophysiology of diseases such as JPS and provide a means of assessing new therapeutics and exploring the genetic and environmental factors that contribute to the disease. Our company offers a variety of services for the development of animal models that serve as a means of aiding in the formulation of effective therapies.
In animals, transgenic or gene editing technology can be used to knock down or edit genes associated with JPS.
Optional models: Smad4 knockout model, Bmpr1a knockout model, etc.
Protheragen evaluates the efficacy and safety of novel drug candidates by carrying out detailed pharmacokinetics analysis coupled with biosafety evaluation studies. We have adopted a collaborative approach with clients that greatly improves communications and allows for personalized support and customized strategies that address the particular needs of the client. In case you wish to know more about our services, do not hesitate otherwise to reach out to us.
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All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.