Composition for treating ischemic diseases or neuroinflammatory diseases, comprising secretome of neural precursor cells as active ingredient
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10688135-B2
Publication Date
2020-06-23
Expiration Date
Abstract
The present invention provides a composition for treating ischemic diseases or neuroinflammatory disorders, comprising a secretome of neural precursor cells (NPCs) as an active ingredient. The secretome of NPCs, of the present invention, reduces an ischemic injury site and enables neurological functions to recover by means of roles such as anti-inflammation, neovascularization regeneration, and activation and proliferation of inherent stem cells, thereby being usable as a therapeutic agent for ischemic diseases and degenerative nervous system disorders such as nerve damage diseases caused by inflammation. Particularly, the secretome of NPCs, of the present invention, has an excellent behavior improvement effect when administered multiple times.
Core Innovation
The invention provides a therapeutic approach using a secretome derived from poly-sialylated neural cell adhesion molecule (PSA-NCAM)-positive neural precursor cells (NPCs). The method administers, to a subject, a therapeutically effective amount of the PSA-NCAM-positive NPC secretome together with a pharmaceutically acceptable carrier for treatment of ischemic cerebrovascular disease and other listed diseases and injuries. The secretome is provided in a form of a cell conditioned medium obtained by culturing NPCs in a cell culture medium and then removing the cells.
The disclosure further supports that the PSA-NCAM-positive NPC secretome can be generated from pluripotent-stem-cell-derived NPCs and that the composition can be administered in repeated (multiple-dose) administration. The invention addresses ischemic and neuroinflammatory diseases and improves outcomes following ischemic injury of the nervous system by reducing ischemic injury and neuroinflammatory responses at lesion sites and supporting functional recovery.
The provided examples report lesion-site changes including reduced ED-1+ microglia and reduced GFAP+ astrocytes, increased DCX+ migrating neural precursor cells, and increased angiogenesis indicated by α-SMA+ vessels. Additional example reporting includes behavioral recovery assessed with a battery of functional tests in a spinal cord injury model.
Claims Coverage
The independent claim covers a method of treating multiple listed conditions by administering a therapeutically effective amount of a PSA-NCAM-positive NPC-derived secretome in the form of cell conditioned medium, together with a pharmaceutically acceptable carrier. The inventive features center on the source (PSA-NCAM-positive NPCs), the secretome format (cell conditioned medium obtained by culturing and removing cells), and the treatment of the listed diseases and injuries.
Treating ischemic and neurodegenerative conditions with PSA-NCAM-positive NPC secretome
A method for treating ischemic cerebrovascular disease, ischemic heart disease, myocardial infarction, Alzheimer's disease, Parkinson's disease, Lewy body disease, multiple sclerosis, amyotrophic lateral sclerosis, or spinal cord injury by administering to a subject a therapeutically effective amount of a secretome derived from PSA-NCAM-positive neural precursor cells (NPCs) and a pharmaceutically acceptable carrier.
Secretome as cell conditioned medium from culturing and removing cells
The secretome is in a form of a cell conditioned medium obtained by culturing neural precursor cells in a cell culture medium and then removing the cells.
PSA-NCAM-positive NPC selection from neural rosettes using anti-PSA-NCAM antibody
PSA-NCAM-positive neural precursor cells are separated from neural rosettes using an anti-PSA-NCAM antibody, where the rosettes are differentiated from pluripotent stem cells.
Pluripotent stem cell source for rosette differentiation
The pluripotent stem cells are embryonic stem cells, induced pluripotent stem cells (iPSCs), embryonic germ cells, or embryonic carcinoma cells.
Multi-dose administration of the secretome composition
The composition is formulated for multi-dose administration.
Secretome constrained by enumerated protein constituents
The secretome comprises a specified set of proteins including agrin, annexin A5, basigin (BSG), biglycan, and many others listed in the claim.
Overall, the claim set is centered on administering a PSA-NCAM-positive NPC-derived secretome as cell conditioned medium, with dependent claims refining PSA-NCAM-positive NPC selection from neural rosettes, the pluripotent stem cell source, multi-dose administration, and secretome protein constituents.
Stated Advantages
Reduces infarct/ischemic injury and improves neurological/functional outcomes at lesion sites following ischemic injury.
Produces stronger effects with repeated (multiple-dose) administration.
Reduces inflammatory and glial responses indicated by reduced ED-1+ microglia and reduced GFAP+ astrocytes.
Increases neural precursor cell migration indicated by increased DCX+ migrating neural precursor cells.
Improves angiogenesis indicated by increased α-SMA+ vessels.
Supports behavioral recovery in a spinal cord injury model with improved outcomes in behavioral tests including the BBB test.
Documented Applications
Treatment of ischemic stroke in a permanent MCAO (pMCAO) model, with reported lesion-site and marker changes including microglia and astrocyte reduction, DCX+ cell increases, and α-SMA+ angiogenesis changes.
Treatment of spinal cord injury (SCI), with behavioral recovery outcomes reported using a BBB test and additional behavioral tests (mNSS, beam balance, prehensile traction, foot-fault, line cross, torso twisting, rearing).
Treatment of ischemic cerebrovascular disease as part of the listed conditions covered by the method claims.
Interested in licensing this patent?