Determining the Role of Notch in Steroid Resistant Nephrotic Syndrome
Research type
Research Study
Full title
Determining the Role of Canonical Notch Signalling in the Regulation of the Glucocorticoid Receptor in Steroid Resistant Nephrotic Syndrome
IRAS ID
131308
Contact name
Aoife M Waters
Contact email
Sponsor organisation
Great Ormond Street Hospital NHS Foundation Trust
Research summary
Scarring of the glomerulus (glomerulosclerosis, GS) can cause terminal kidney disease. Glucocorticoid treatment has a beneficial effect but resistance (GR) develops over time. Alternative treatments are available with significant side effects and only 30-60% of patients respond. Consequently, new treatments are needed. Recently, we have shown that activation of a critical signalling pathway (Notch) is involved in initiating glomerular scarring. Using knockout mouse models and drugs which block the pathway, we and others, have shown that glomerular scarring can be prevented. Studies in leukaemic patients have shown that Notch activity can inhibit the glucocorticoid response, an effect which can be reversed by inhibiting Notch. This study aims to determine whether Notch activation is evident in kidney biopsy samples from patients with steroid resistant nephrotic syndrome a disease associated with glomerular scarring. Archived diagnostic samples of kidney biopsies with a histological diagnosis of glomerulosclerosis will be investigated to determine whether expression of the Notch, effector, HES-1 is increased compared to control samples taken from archived diagnostic tissue of protocol renal transplant biopsies.
REC name
North East - York Research Ethics Committee
REC reference
13/NE/0219
Date of REC Opinion
11 Jul 2013
REC opinion
Favourable Opinion