Therapeutic Area Hematological cancers/disorders (transplantation)
Indication

Hematologic malignancies, bone marrow failure conditions, a variety of congenital diseases and autoimmune diseases (conditions requiring hematopoietic stem cell (HSC) transplantation as a treatment)

Objective

To identify novel agonists to be used alone or in combination for expansion of human HSCs

Stage of Development Pre-clinical studies
Type of Target Hematpoietic stem cells
IP Status PCT application filed
Principal Investigator Guy Sauvageau
Type of Partnership Sought Licence, co-development or other

Competitive Advantages

• Optimized ex vivo expansion of HSCs through the use of small molecules i.e. easier production than biological compounds

• Access to the unique expertise of the Principal Investigator in hematopoietic stem cell characterization

• Identification of small molecule compounds with both short-term and long-term hematopoietic repopulating potential, and positive pre-clinical data

Hemopoietic stem cells (HSCs) are rare cells capable of sustained production of all blood cell types. However, HSC division can also generate two identical daughter cells in a process called self-renewal, and this HSC property is essential for successful bone marrow transplantations that can be used to treat various blood diseases. Only approximately 1/3 of patients who are in need for bone marrow transplantation can find a suitable donor, and many of them die before finding a match. Expansion of patients’ own (autologous) HSCs, or HSCs isolated from cord blood, could become an alternative to finding a matched donor. Identification of conditions required for expansion of normal functional HSC outside of the body, or ex vivo, has had some very limited success. We have identified small molecules, which, in addition to various nutrients and cytokines, appear to promote such HSC expansion. These molecules also cooperate with the only previously identified HSC-stimulating compound to enhance HSC production above the levels achieved by any of these substances alone. Currently, we are exploring the possibility that small changes in structure of these molecules could further improve their HSC-expanding ability. Using various analytical techniques we are also trying to understand how these compounds trigger changes in cellular behaviour, and which cellular components are required for these changes to occur.

A potent structure  has been generated and is currently used to carry out the biological and preclinical studies of the project. At this stage, all the toxicology and pharmacology studies required for the preparation of a preclinical package have been performed and the results are very encouraging. The ability of the compound to expand HSC test has been confirmed through various models and the focus is now on the identification of the cellular target of the compound.