Use of stem cells expressing mesenchymal and neuronal markers and compositions thereof to treat neurological disease
Inventors
Kerkis, Irina • Valverde Wenceslau, Cristiane
Assignees
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Publication Number
US-11278574-B2
Publication Date
2022-03-22
Expiration Date
Abstract
The invention provides pharmaceutical compositions comprising human immature dental pulp stem cells (hIDPSCs) wherein the hIDPSCs express CD44 and CD13. The invention also provides methods of treating a neurological disease or condition comprising systemically administering to a subject a pharmaceutical composition comprising hIDPSCs wherein the hIDPSCs express CD44 and CD13. For example, for treating neurological diseases or conditions including supporting the neuro-protective mechanism in subjects diagnosed with early HD or repairing lost DA neurons in subjects diagnosed with PD.
Core Innovation
The invention relates to a method of promoting neuronal growth and repair, reducing neuronal loss, or both in the central nervous system (CNS) of a subject by administering a pharmaceutical composition comprising human immature dental pulp stem cells (hIDPSCs). The hIDPSCs express CD44 and CD13, and at least 80% of the hIDPSCs express brain-derived neurotrophic factor (BDNF).
The described approach addresses CNS conditions characterized by neuronal loss by providing hIDPSCs with neurotrophic activity and the therapeutic outcome of preventing neuron loss and promoting neurogenesis and neuroprotection. The document also describes systemic administration, including intravenous (IV) administration in relevant contexts.
The invention further incorporates cell characterization and safety-related constraints for the hIDPSCs used in the pharmaceutical composition, including absence of teratoma formation and absence of chromosomal aberration as described, and in certain aspects absence of HLA-DR and HLA-ABC.
Claims Coverage
The independent claim set includes 1 independent claim. The inventive features center on the composition-defined hIDPSC immunophenotype and neurotrophic output threshold, applied to promoting neuronal growth and repair and/or reducing neuronal loss in the CNS.
CNS neuronal growth and repair with BDNF-expressing hIDPSCs
A method of promoting neuronal growth and repair, reducing neuronal loss, or both in the central nervous system (CNS) of a subject, comprising administering to the subject a pharmaceutical composition comprising human immature dental pulp stem cells (hIDPSCs), wherein the hIDPSCs express CD44 and CD13, and at least 80% of the hIDPSCs express brain-derived neurotrophic factor (BDNF).
Overall, the claim coverage focuses on systemic administration of a pharmaceutical composition containing hIDPSCs defined by CD44 and CD13 expression and a high fraction expressing BDNF, for promoting neuronal growth and repair and/or reducing neuronal loss in the CNS.
Stated Advantages
Promotes neuronal growth and repair, reducing neuronal loss, or both in the CNS.
Promotes neuronal growth and repair in the CNS.
Reduces neuronal loss in the CNS.
Increases dopamine receptor D2 expression and BDNF expression in hIDPSC-treated animals in the 3-NP Huntington’s disease model.
Indicates differentiation into mature GABAergic spiny neurons and supports neurogenesis.
Attenuates weight loss and improves survival in the 3-NP model with fewer deaths/early mortality limited to 3-NP toxicity and no additional deaths after repeated hIDPSC dosing.
Documented Applications
Application to Huntington’s disease using a 3-nitropropionic acid (3-NP) rat model, with evaluation via dopamine receptor D2 and BDNF readouts, including striatum and subventricular zone analyses.
Mentioned additional treatment outcomes for veterinary CDV-like disease in dogs.
Preventing neuron loss and promoting neurogenesis and neuroprotection in central nervous system diseases such as Parkinson’s disease and Huntington’s disease using systemic administration, including intravenous (IV) administration.
Reducing neuronal loss and promoting neuronal growth and repair in a CNS context assessed with biomarkers and brain expression outcomes including DARPP-32 and D2 receptor expression and BDNF-related expression.
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