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Please note that we provide research services and do not offer diagnostic and therapeutic services for individuals.

Hirschsprung Disease

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Hirschsprung disease is considered one of the rarest forms of congenital intestinal disease. It is defined by the absence of ganglion cells in the myenteric and submucosal plexuses of the intestine. It leads to distal functional obstruction which may culminate in complications like enterocolitis. In our company, as one of the foremost service providers, Protheragen is concentrated on fully offering research solutions for developing therapeutic interventions for Hirschsprung disease.

Overview of Hirschsprung Disease

Hirschsprung disease is a unique birth defect that lacks ganglion cells in the myenteric plexus of the distal bowel. The absence of ganglion cells translates into a structural obstruction of the bowel leading to constipation, abdominal distention, vomiting, and other signs of obstruction. Most of these individuals, approximately 80% of cases, have a diagnosis in the neonatal period, typically with the first passage of meconium delayed beyond 24 hours. Its prevalence is between one to two point six cases per 10,000 live births, and it occurs more frequently in boys compared to girls.

Distal ileum biopsy in an individual with eosinophilic enteritis.

Fig.1 Timeline of genetic discoveries of Hirschsprung disease. (Tang, C. S., et al., 2023)

Pathogenesis of Hirschsprung Disease

The etiology of Hirschsprung disease is rooted in the improper migration of the vagal neural crest cells during embryogenesis. Additionally, the sacral neural crest contributes to the pelvic plexus neuronal population and may also be involved in the pathology. Many mutations can be associated with this including RET, GDNF, EDNRB, SOX10, and PHOX2B.

2-1-3-11-hirschsprung-disease-2 Fig.2 The 3 zones of the Hirschsprung disease bowel. (Matsukuma, K., et al., 2023)

Therapeutics Development for Hirschsprung Disease

Drug Names	Mechanism of Action	Targets	Research Phase
Vancomycin	Blocking the formation of a cell wall in bacteria results in the death of the bacteria.	Peptidoglycan	Phase III
Enteric neural stem cell transplantation	Improvement of intestinal movement as well as the severity of Hirschsprung-associated enterocolitis was reduced.	/	Preclinical
Glial cell derived neurotrophic factor	Regeneration of neural tissue and restored structure and function of the colon.	/	Preclinical
hPSC-derived ENS precursors	Reduce GI functional abnormalities and possibly eliminate the need for surgical resection.	/	Preclinical

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

The comprehensive services of our company cover the entire spectrum of drug development, from initial discovery through preclinical research stages, to accelerate the advancement of therapeutics for this challenging condition. Through the development of relevant in vitro and in vivo disease models, we rigorously evaluate the efficacy and safety profiles of potential drug candidates so that the chances of successful commercialization are significantly improved.

Therapeutic Development Services

Animal Model Development Services

Studying the pathophysiology, genetics, and possible therapeutics for Hirschsprung disease thoroughly requires animal models. For Hirschsprung disease, we provide full services in the development and testing of animal models to facilitate preclinical drug discovery and development.

Induced Models

Embryonic or neonatal stages can be chemically induced to model Hirschsprung disease by introducing chemical agents that interfere with the development or survival of the enteric nervous system.

Treated benzalkonium chloride (BAC) into the animals via enema caused distal colon stenosis and proximal colon enlargement.
Administration of a phosphoramidon to disrupt the establishment of a functional ENS.

Surgery Models

Surgical models aim to reproduce the effects of Hirschsprung disease pathology in animals by mechanically removing or damaging enteric neurons within their intestines.

For instance, one could take a segment of the jejunum and subject it to BAC chemical denervation and then perform a bypass jejunojejunostomy to restore intestinal continuity.

Genetically Engineering Models

Genetically modified animal models are among the most widely used in Hirschsprung disease research, which involve mutations in genes critical for ENS development.

Ret knockout model
Ednrb knockout model
Phox2B knockout model

Sox10 mutant model
Ece1 knockout model
Others

Through the application of technology and specialized expertise, Protheragen offers a complete range of services which includes pharmacokinetic studies and biosafety assessment services, to speed up new therapies that enhance the Hirschsprung disease individual's quality of life. Should you be interested in our services, please get in touch to receive additional details.

References

Tang, Clara Sze-Man et al. "Genetics of Hirschsprung's disease." Pediatric surgery international 39.1 (2023): 104.
Matsukuma, Karen et al. "Hirschsprung Disease for the Practicing Surgical Pathologist." American journal of clinical pathology 159.3 (2023): 228-241.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.