Developing a Nrf2 activator for the treatment of scleroderma

Project: Research project

Project Details

Description

Scope of work for Phase I STTR application: Developing a Nrf2 activator for the treatment of scleroderma.
The project described in this proposal is a one year collaboration between Cureveda LLC and Dr. John Varga’s laboratory at Northwestern.
VEDA-1209 is a specific, potent, orally available Nrf2 activator that is being developed by Cureveda for several autoimmune, inflammatory and neurodegenerative diseases. The goal of the current Phase I STTR project is to conduct key proof of concept studies that include testing VEDA-1209’s anti-fibrotic activity in human skin biopsies from scleroderma patients, as well as its efficacy in two animal models of scleroderma. The results will help determine the potential for Nrf2 activators to modify the pathology of scleroderma and will form the basis for further development of VEDA-1209 as a novel treatment for this disease.
Cureveda and Northwestern have the following responsibilities under each Specific Aim:
Specific Aim 1: Test VEDA-1209 for activity against a panel of human skin fibroblast cultures from 20 scleroderma patients and 10 healthy volunteers. The fibroblast cultures will be obtained by Northwestern and tested: (a) for levels of Nrf2 activation following treatment with VEDA-1209 (studies carried out at Cureveda); and (b) for the effect of VEDA-1209 on mitigating fibrotic responses induced by TGF-ß, and constitutive fibrotic signaling (studies carried out at Northwestern). These studies will also help define the doses used in Aim 2.
Specific Aim 2: Test VEDA-1209’s efficacy in two mouse models of scleroderma: (i) Prevention and regression of skin and lung fibrosis induced by subcutaneous bleomycin; and (ii) Prevention of skin fibrosis induced by overexpression of constitutively active type 1 TGF-β receptor. These studies will be carried out at Northwestern with analysis of samples at Cureveda (Nrf2 activation) and Northwestern (effect of VEDA-1209 treatment on skin and lung fibrosis and inflammation)
If the results of this Phase I project are supportive, we will apply for a Phase II STTR under which we would carry out additional animal and in vitro efficacy studies, as well as IND-enabling studies to support the subsequent initiation of clinical trials in scleroderma patients.
StatusFinished
Effective start/end date9/7/148/31/15

Funding

  • Cureveda, LLC (Agr. FE 11/11/2014//1R41AR066418-01)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (Agr. FE 11/11/2014//1R41AR066418-01)

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