Background

CDH is a congenital malformation of the diaphragm that involves three major fetal defects: (1) failure of the diaphragm to completely close during development, (2) herniation of the abdominal contents into the chest and, (3) pulmonary hypoplasia.

Infants with CDH experience respiratory failure as a result of pulmonary hypertension and pulmonary hypoplasia. In the US alone, ~1,600 infants are born with CDH every year, or 1 in every 2,500 live births, a rate similar to that seen for Cystic Fibrosis or Spina Bifida. While surgical interventions can repair the defect, the associated pulmonary hypoplasia and abnormal lung vascular development can result in substantial morbidity and mortality. With an average mortality rate of 20-30%, many CDH survivors require intensive neonatal care and often present with long-term morbidity.

Technology Overview

The following technologies were developed in the lab of researchers at the University of Manitoba’s, Departments of Surgery, Pediatrics & Child Health and Physiology & Pathophysiology. Pediatric Surgeon/Scientist:

Panel of circular RNA biomarkers present in maternal fluids that may allow physicians to more accurately determine if a fetus diagnosed with CDH would benefit from a prenatal surgical intervention (fetoscopic endoluminal tracheal occlusion).
An miRNA therapeutic, which when administered prenatally to the mother, can prevent congenital malformation of the diaphragm and associated pulmonary hypoplasia seen in CDH. This may remove the need for surgical interventions in pediatric patients.

These related discoveries are covered by an issued US patent (US9914971) as well as a follow-on US provisional patent application (filed 14 October 2020).

Unique Tracheal Fluid MicroRNA Signature Predicts Response to FETO in Patients With Congenital Diaphragmatic Hernia. Pereira-Terra P et al. Ann Surg. 2015 Dec;262(6):1130-40.

MicroRNA 200b is upregulated in the lungs of fetal rabbits with surgically induced diaphragmatic hernia. Eastwood MP et al. Prenat Diagn. 2018 Aug;38(9):645-653.

Prenatal microRNA miR-200b Therapy Improves Nitrofen-induced Pulmonary Hypoplasia Associated With Congenital Diaphragmatic Hernia. Khoshgoo N et al. Ann Surg. 2019 May;269(5):979-987.

Can circular RNAs be used as prenatal biomarkers for congenital diaphragmatic hernia? Wagner R et al. Eur Respir J. 2020 Feb 27;55(2):1900514.

miR-200 family expression during normal and abnormal lung development due to congenital diaphragmatic hernia at the later embryonic stage in the nitrofen rat model. Mulhall D et al. Pediatr Surg Int. 2020 Dec;36(12):1429-1436.

Benefits

Circular RNA biomarkers present in maternal fluids are more accurate than prenatal Ultrasound or MRI in diagnosing CDH and in calculating the chance of success for prenatal surgical interventions.

The ability to predict the survival of patients undergoing prenatal tracheal surgical interventions more accurately will allow clinicians to determine in advance if future interventions will be required.

The use of a prenatal non-surgical intervention may significantly reduce the morbidity and mortality associated with CDH, while also decreasing the level and length of neonatal care required after birth.

Applications

These technologies can be used for more accurate prenatal diagnosis the development of Congenital Diaphragmatic Hernias and as well as design prenatal treatments that may avoid the need for surgical interventions in these patients.

Opportunity

The University is actively seeking a partner to move this technology to market, through either licensing or via investment into Sponsored Research to develop a Preclinical Testing program.

The University also welcomes interactions with any investor or entrepreneur that would like to license the patent to create a start‑up.

Non-Surgical Treatment of Congenital Diaphragmatic Hernias (CDH)

Patents

IP Status

Seeking