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Novel Gremlin-1 Mutants as therapeutics in Diabetic Kidney Disease (360G-Wellcome-202395_Z_16_Z)

Diabetic kidney disease affects ≈40% of those with diabetes and is the leading cause of end stage renal disease. Current therapies focusing on regulation of glycaemia, hypertension and RAAS blockade are inadequate, merely slowing progression to eventual organ failure. Given the increased prevalence and devastating consequences of DN there is an urgent need to develop novel therapies. The development of fibrosis, a key pathogenic factor in DN, reflects an imbalance in the activities of endogenous drivers and suppressors of fibrosis typified by the BMP agonist-antagonist system. Prof.Godson’s group previously reported that the BMP antagonist Gremlin-1 is a key driver of DN in experimental models and human disease. Increased Gremlin-1 expression drives fibrotic responses of renal cells antagonizing the activity of BMP agonists. Prof.Godson's group have used in silico tools to design Gremlin-1 molecules which are functional dominant negatives[FDN]. These molecules are expected to bind Gremlin-1 and not agonists, therefore allowing local bioavailability of endogenously generated agonist, thus limiting fibrosis. Prof.Godson's group have expressed these molecules in mammalian cells. We propose to evaluate these novel FDN Gremlin-1 using established in vitro models of DN and renal fibrosis routinely used in Dr.Crean’s laboratory. Such data will identify their utility as therapeutics.


01 Apr 2016

Grant details
Amount Awarded 2000
Applicant Surname Phelan
Approval Committee Internal Decision Panel for C&S
Award Date 2016-04-01T00:00:00+00:00
Financial Year 2015/16
Grant Programme: Title Vacation Scholarships
Internal ID 202395/Z/16/Z
Lead Applicant Mr David Phelan
Planned Dates: End Date 2016-07-23T00:00:00+00:00
Planned Dates: Start Date 2016-05-23T00:00:00+00:00
Recipient Org: Country Ireland
Region Ireland
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