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The Jaundice Chip: A diagnostic tool for cholestatic liver disease

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
80426
Program Year/Program:
2007 / STTR
Agency Tracking Number:
DK075162
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
P2D, INC.
10101 Alliance Rd CINCINNATI, OH 45242-
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 2
Fiscal Year: 2007
Title: The Jaundice Chip: A diagnostic tool for cholestatic liver disease
Agency: HHS
Contract: 2R42DK075162-02
Award Amount: $699,155.00
 

Abstract:

DESCRIPTION (provided by applicant): Cholestasis (pathologic jaundice) is a very common sign of liver disease in children and adults, and results from genetic defects that play a critical role in bile formation and transport. In adults, mutations in the sa me genes also cause debilitating liver diseases or increased susceptibility to common biliary diseases, such as gallstones. Because many of the clinical signs and symptoms are shared among these disorders, many laboratory studies and liver biopsies are nec essary before specific diagnosis is made. Despite remarkable progress understanding how these genes cause liver disease in humans, the new knowledge has so far failed to result in a practical method of diagnosis or improved treatment of these patients. To translate this knowledge into the clinical arena, we developed a gene chip to identify mutations in the five genes that cause the most common forms of inherited syndromes of chronic cholestasis: The Jaundice Chip. The Chip uses a state-of- the-art reseque ncing platform that enables the readout of several thousand nucleotides in one reaction. In a Phase I award that now nears completion, we tested the technical merit of the Jaundice Chip. We found that the Chip efficiently reads the sequence of target gene s efficiently and with 99.99% accuracy. We also found that it surveys for gt95% of all mutations caused by single nucleotide changes. In this Phase II application, we propose to bench-test the Jaundice Chip against a larger patient population to demonstrat e its clinical application as a reliable, high-throughput diagnostic tool for patients with chronic liver disease. In Aim 1, we will determine the ability of the Jaundice Chip to identify insertion and deletion mutations by directly analyzing the sequence readout from patients known to have inherited forms of intrahepatic cholestasis due to these types of mutations. In Aim 2, we will bench-test the Chip as a biomarker of disease by performing a prospective genotype-phenotype relationship in subjects with ch ronic cholestasis, and by determining whether the Chip can identify genetic markers of clinical response to treatment. And in Aim 3, we will develop an informatics-based analytical tool that optimizes mutation detection by the Jaundice Chip. To assure comp letion of these aims in a timely fashion, P2D Inc. has assembled a suitable investigative team that combines expertise in the field with a business infrastructure to transform the highly innovative features of the Chip into a non-invasive diagnostic tool t hat significantly improves the diagnostic algorithm in patients with liver disease. Jaundice is a clinical sign that is common to several types of chronic liver diseases in children and adults. Despite the significant advances in understanding the genetic basis of jaundice in humans, the new knowledge has so far failed to result in a practical method of diagnosis or improved treatment of these patients. To translate this knowledge into practical medial applications in the clinical arena, we developed a gene chip to identify mutations in the five genes that cause the most common forms of inherited syndromes of persistent jaundice (also known as cholestasis). The chip, named Jaundice Chip, uses a state-of-the-art technology that enables the detection of muta tions of selected genes. In the Phase I award that now nears completion, we demonstrated the technical merit of the Jaundice Chip as a efficient and highly accurate gene sequencing tool. In this Phase II application, we propose to bench-test the Jaundice C hip against a larger patient population to demonstrate its clinical application as a reliable, high-throughput diagnostic tool for patients with chronic liver disease. These studies will lead to opportunities to transform the highly innovative features of the Chip into a non-invasive diagnostic tool that significantly improves the diagnostic algorithm in patients with liver disease.

Principal Investigator:

Jorge A. Bezerra
5136363008
JORGE.BEZERRA@CCHMC.ORG

Business Contact:

Frank Xemlan
rmooconnor@p2dinc.com
Small Business Information at Submission:

P2D, INC.
P2D, INC. 3130 HIGHLAND AVE, 3RD FL CINCINNATI, OH 45219

EIN/Tax ID: 202224724
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Research Institution Information:
CHILDREN'S HOSPITAL MEDICAL CE
CHILDREN'S HOSPITAL
3020 CHILDREN'S WAY
SAN DIEGO, CA 92123-4223
RI Type: Domestic nonprofit research organization