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Sarm1 and diabetic complications in adolescents with type 1 diabetes
Summary Data Summary
Applicant Scheller, Erica
E-Mail Address scheller@wustl.edu
Project Title Sarm1 and diabetic complications in adolescents with type 1 diabetes
CBU ID 21AU4173
External SubContract ID 32307-86
Diabetic Complication All Complications
Funding Program Group Pilot & Feasibility [PF2021]
Abstract In America, there are 1.6 million people living with type 1 diabetes (T1D),
including nearly 200,000 children and adolescents. Young adults with T1D often
have difficulty maintaining adequate glycemic control relative to other age
groups, putting them at increased risk for early development of diabetic
complications in systems including nerve and bone. Therapies that can be used to
simultaneously prevent or to reverse multiple diabetic complications during
times of glycemic instability, beginning in childhood and adolescence and
continuing throughout the lifespan, are needed to promote lifelong health and
healthy aging in patients with T1D. Sarm1 (sterile a and TIR motif-containing
protein-1) is homomultimeric cytoplasmic protein with NADase and ADP-ribosyl
cyclase activity. Sarm1 is a metabolic biosensor that is activated by injury,
inflammation, and oxidative stress. When activated, Sarm1 promotes the
progression of diabetic peripheral neuropathy. In addition, we have recently
discovered that Sarm1 drives bone loss and skeletal instability in mice with
T1D. Progression of DPN often tracks with fracture risk, suggesting shared
underlying mechanisms of development and/or direct relationships between nerve
and bone health. In humans, as in mice, we hypothesize that increases in Sarm1
expression and activation occur in adolescents with poorly controlled T1D in
response to inadequate glycemic control, contributing to the early onset and
progression of diabetic complications in nerve and bone. To test this hypothesis
while obtaining foundational preliminary data for future longitudinal studies,
we will pursue two specific aims. First, we will quantify Sarm1 expression and
activation in adolescents with T1D relative to non-diabetic controls. Second, we
will explore the relationship between Sarm1, neuropathy, and bone quality. This
is timely because Sarm1 inhibitors are currently in preclinical development for
treatment of peripheral nerve damage. Our goal is to define young patients with
T1D that may benefit from future use of Sarm1 inhibitors as a clinical strategy
to prevent diabetic complications across multiple systems including nerve and
bone.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel Erica Scheller
Salary Total Costs 50487
Supply Total Costs 4040
Equipment Total Costs 0
Travel/Other Total Costs 8722
Direct Costs 63249
Indirect Costs Proposed 36368
Total Costs Proposed 99617
Total Costs Approved 99617
Start Date 7/1/2021
End Date 6/30/2022
IFO Name Medley, Teri
IFO E-Mail Address researchgrants@wusm.wustl.edu
IACUC/IRB No. 201908120
IACUC/IRB Institution Washington University in St Louis
Entity ID No. 1430653611A1
Report Request Date 6/30/2022
T1D YES
TypeCount
Invoices 9
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  21AU417332307-86Washington University in St Louis8/26/2022$9,411.27$5,391.80$14,803.07$40.34View PDF
  View  21AU417332307-86Washington University in St Louis6/1/2022$6,069.11$3,489.75$9,558.86$40.34View PDF
  View  21AU417332307-86Washington University in St Louis5/17/2022$9,018.91$5,151.37$14,170.28$40.34View PDF
  View  21AU417332307-86Washington University in St Louis4/1/2022$6,758.12$3,881.02$10,639.14$40.34View PDF
  View  21AU417332307-86Washington University in St Louis3/3/2022$6,909.93$3,957.24$10,867.17$40.34View PDF
  View  21AU417332307-86Washington University in St Louis2/9/2022$5,551.76$3,192.31$8,744.07$40.34View PDF
  View  21AU417332307-86Washington University in St Louis11/27/2021$4,368.50$2,511.89$6,880.39$40.34View PDF
  View  21AU417332307-86Washington University in St Louis10/19/2021$5,074.86$2,918.06$7,992.92$40.34View PDF
  View  21AU417332307-86Washington University in St Louis1/9/2022$10,108.37$5,812.39$15,920.76$40.34View PDF


Reports
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