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Evaluating the efficacy of MSI-1436 in slowing the progression and in reversing diabetic nephropathy in the BTBR ob/ob mouse
Summary Data Summary
Applicant Yin, Viravuth
E-Mail Address voot.yin@novobiosciences.com
Project Title Evaluating the efficacy of MSI-1436 in slowing the progression and in reversing
diabetic nephropathy in the BTBR ob/ob mouse
CBU ID 18AU3892
External SubContract ID 32307-29
Diabetic Complication Nephropathy
Funding Program Group Pilot & Feasibility [PF2018]
Abstract Abstract Diabetic nephropathy (DN) is a major cause of morbidity and mortality
in type 1 diabetics and is becoming an increasingly serious problem in type 2
diabetics. DN is characterized by progressive loss of glomerular function due to
fibrosis, capillary damage and loss of podocytes and is the primary cause of
chronic and end-stage renal disease in the world. Therapies aimed at inducing
the regeneration of lost tissues and cells have been proposed as therapeutic
strategies for slowing and reversing diabetic glomerular damage. MSI-1436 is a
readily synthesized aminosterol isolated from dogfish sharks. We have
demonstrated that MSI-1436 induces a 2-3-fold stimulation in regeneration of
amputated zebrafish cardiac, nerve, bone, skin, connective and vascular tissues
without malformation. In adult mice, MSI-1436 stimulates injured skeletal muscle
stem cell activation over 2-fold, and increases survival, improves heart
function ~2-fold, stimulates regenerative cardiomyocyte proliferation ~4-fold
and reduces infarct size by ~55% 4 weeks after cardiac ischemic injury induced
by permanent cardiac artery ligation. MSI-1436 has been studied extensively. The
molecule inhibits the tyrosine phosphatase PTP1B and was tested by Genaera Corp.
in 2007 in Phase 1 and 1b clinical trials for treatment of obesity and type 2
diabetes. Metabolic changes consistent with inhibition of PTP1B were reported
and patients showed no adverse reactions to the drug. Importantly, the
stimulatory effects on tissue repair and regeneration we observe in zebrafish
and mice occur at doses 5- and 50-times lower than the maximum dose shown
previously to be safe in humans. Given the effect of MSI-1436 on animals as
diverse as zebrafish and mice and its ability to stimulate repair and
regeneration of highly diverse tissues, we postulate that the molecule will
stimulate the regeneration of diverse cell types in the diabetic kidney. The
overall Aim of this pilot project application is to carry out a proof-of-concept
study to test the efficacy of MSI-1436 in slowing and reversing glomerular
damage in the BTBR ob/ob mouse. Demonstrated efficacy will provide an essential
foundation for more in-depth preclinical studies in order to establish whether
MSI-1436 is a candidate for clinical evaluation. The demonstrated safety of
MSI-1436 and extensive knowledge of its target and mode of action greatly reduce
the time and costs associated with developing this molecule as a regenerative
medicine therapy.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 45500
Supply Total Costs 21860
Equipment Total Costs 0
Travel/Other Total Costs 0
Direct Costs 67360
Indirect Costs Proposed 26944
Total Costs Proposed 94304
Total Costs Approved 94304
Start Date 11/1/2018
End Date 10/31/2019
IFO Name Strange, Kevin
IFO E-Mail Address kevin.strange@novobiosciences.com
IACUC/IRB No. 99999
IACUC/IRB Institution Novo Biosciences
Entity ID No. 46-2171255
Report Request Date 11/29/2019
T1D NO
TypeCount
Invoices 5
Progress Reports 2
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  18AU389232307-29Novo Biosciences9/14/2020$24,725.01-$24,725.01$0.02View PDF
  View  18AU389232307-29Novo Biosciences7/10/2020$21,501.75-$21,501.75$0.02View PDF
  View  18AU389232307-29Novo Biosciences4/14/2021$14,249.45-$14,249.45$0.02View PDF
  View  18AU389232307-29Novo Biosciences3/13/2020$8,721.54-$8,721.54$0.02View PDF
  View  18AU389232307-29Novo Biosciences1/4/2021$25,106.23-$25,106.23$0.02View PDF
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