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Noninvasive Diagnostic for Early Prognosis and Diagnosis of Organ Rejection

Description:

Method for early prediction of acute and chronic rejection of a transplanted organ by analyzing exosomes specific to transplanted organ in recipient’s biological fluids.

 

Inventor:

Prashanth Vallabhajosyula, MD

 

Problem:

Transplantation remains the only curative therapy for patients with end stage failure of the heart, lung, kidney, liver and pancreatic β cells (biabetes). Immunologic rejection and complications associated with immunosuppressive regimen are the major causes of morbidity and mortality in transplant patients. Yet to this date, there is no accurate, time sensitive, noninvasive biomarker to monitor for transplant organ rejection/ injury.  For example, heart transplant recipient undergoes 17 heart biopsies during the first 2 years; lung transplant recipient undergoes 4-8 bronchial biopsies during the first year.  Therefore, there is a critical need for non-invasive biomarker platforms for monitoring transplant status. 

 

Solution:

Exosomes are extracellular microvesicles released by many tissue types into bodily fluids.  They carry tissue specific RNA and protein cargoes reflecting the conditional status of the originating tissue. Dr. Vallabhajosyula at Penn showed that transplanted tissues release donor organ specific exosomes into recipient circulation/bodily fluids that can be tracked over long-term follow-up. Inventor successfully used donor-recipient major histocompatibility complex (MHC) mismatch to isolate and purify transplant-specific exosomes. Transplant rejection led to significant reduction in the exosome signal in a time-specific manner along with distinct changes in its microRNA and proteomic profiles. For example, in an islet transplant model, plasma transplant islet exosome signal in acute rejection decreased on day 1 while currently used standards (fasting glucose and glucose tolerance test) showed abnormality on day 6 (100% sensitivity and specificity). In a heart transplantation model, donor heart exosome signal was significantly decreased by day 2 of acute rejection, well before clinical and histological changes of rejection (day 11).  Therefore, analysis of transplant-specific exosomes might provide a time-sensitive, non-invasive biomarker platform for monitoring organ rejection/ injury.

 

 

 

Applications:

•       Isolation, purification, quantification and analysis of donor-specific exosomes

•       Monitoring transplant status using exosome signal and RNA/proteome signature

•       Titration of the immunosuppressive treatment doses

•       Novel molecular marker for monitoring transplant organ status

 

Advantages:

•       Highly accurate, non-invasive, time-sensitive

•       Rapid turnover test (<24 hours)

•       Potential reduction of number of biopsies

•       Significantly improved signal to noise ratio compared to platforms based on free nucleic acids and proteins analysis

•       Reduction of false positives associated with collateral injury/stress to other tissues

 

Stage of Development:

•       Islet and renal transplantation: mouse and human clinical data (blood, urine)

•       Heart transplantation: mouse data

 

Intellectual Property:

PCT Pending WO/2016/011383

Reference Media:

under review

       

Desired Partnerships:

License

Co-development

 

 Docket #: Z6576

 

 

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Patent Information:
Category(s):
Diagnostics
For Information, Contact:
Linara Axanova
Associate Director, PSOM Licensing Group
University of Pennsylvania
axanova@upenn.edu
Inventors:
Prashanth Vallabhajosyula
Keywords: