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  • Preclinical development
  • MPN
  • Targeted therapy
  • Alternative therapy
  • Preclinical research (TRL 4-5)

In vivo study models to assess the role of PPAR-Y in the development of bone marrow fibrosis and the progression of hematological malignancies.


Description

Scope of research activities

In myeloid hemopathies, the presence of bone marrow fibrosis is associated with a poor prognosis.  The objectives are: 

  1. To determine whether the presence of fibrosis is a simple indicator, or whether bone marrow remodeling is a pathological player with a direct impact on the natural history of hematological disorders 
  2. To characterize the parameters affected by bone marrow fibrosis
  3. To determine whether treatment of bone marrow fibrosis with a PPARy agonist offers a therapeutic advantage over conventional therapies targeting hematopoietic cells alone
  4. To evaluate combination treatments (PPARy agonists +/- conventional therapy)

Conduct of studies

Steps:

  • Definition of hypotheses and study design.
  • Drafting study plans, calculating headcounts, validating drugs and obtaining regulatory approvals. 
  • Conducting the study
  • Analysis and results communication

Research infrastructure

Experimental and analytical platforms:

  • Flow cytometry
  • Molecular biology
  • Biological safety levels 2 and 3 laboratories
  • Small animal imaging
  • Animal facility

Models :

  • Mouse models of myeloproliferative neoplasia (donor mice)
  • Mouse models of haploinsufficiency or depletion of the Ppar-y gene in marrow mesenchymal stromal cells (recipient mice)

Technical personnel:

  • Animaliance company staff for animal facility management
  • Anatomopathology platform

Specifications

The approach

Mouse models predisposed to bone marrow fibrosis to assess 1) the impact of bone marrow fibrosis on the natural history of hematological diseases, 2) the pro- or anti-fibrosis potential of new molecules.

The studies 

Study of the impact of medullary stromal pre-fibrosis/fibrosis on the natural history of myeloid hemopathies:

  • Analysis and characterization of the role of PPARy in bone marrow mesenchymal stromal cells. Effect on 1) hematopoietic support, 2) homing of hematopoietic cells, 3) susceptibility to the development of bone marrow fibrosis, 4) establishment/non-resorption of an inflammatory syndrome.

Examples of partnerships

Study of the therapeutic potential of PPARgamma nuclear receptor activation in myelofibrosis - Evaluation of a treatment using PPARg agonists in the management of myelofibrosis (in vitro, ex vivo and in preclinical mouse models of the disease).

Partners: UMR 1287; CIC 1427

 


Terms

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