IN VIVO MODEL OF WALDENSTRÖM DISEASE

Preclinical development

Waldenström's macroglobulinemia

Targeted therapy

Preclinical research (TRL 4-5)

Unique WM mouse model, mutated for CXCR4 and MyD88, to assess the impact of treatments on immune cell biology and the bone marrow microenvironment.

First murine model, accurately reproducing key features of Waldenström disease biology, for drug candidate validation.

Description

Scope of research activities

Preclinical research using a WM mouse model, mutated for CXCR4 and MyD88:

Pre- and post-treatment phenotypic and functional analyses
Evaluation of treatments
Mechanism of action

Conduct of studies

Steps :

Study design for innovative products designed to modulate malignant cells and/or their environment
Organization, implementation and conduct of studies
Drafting of study plans.
Statistical analysis and interpretation of results

Research infrastructure

Experimental and analytical platforms:

Spectral flow cytometry (40 simultaneous markers)
Cell culture
Animal facility
Confocal microscopy

Biological resources:

Cxcr4+/1013 x Myd88B-L252P mouse model reproducing certain features of Waldenstrom's disease

Specifications

The platform

Preclinical mouse model with gain-of-function mutations for the Cxcr4 and MyD88 proteins and some Waldenström disease features (hyper IgM, bone marrow involvement, reduced survival).

The studies

Screening of drug candidates targeting the Btk and CXCR4 signaling axes:

IgM production
Clinical signs
Phenotyping of B cells, immune and stromal compartments

Evaluation of treatment activity (or combination of treatments):

IgM production
Clinical signs
Phenotyping of B cells, immune and stromal compartments

Mechanism of action of drug candidate:

B-cell survival and migration
B cell differentiation, signaling and activation
Bone marrow hematopoiesis
Bone marrow microenvironment

Examples of partnerships

CXCR4 antagonism in mouse models for hematological disorders associated with gain-of-CXCR4 function - Impact on how B cells adapt to and shape the bone marrow ecosystem.

Partner : X4 Pharmaceuticals