Granulocyte colony-stimulating factor (GCSF) gene therapy for treating neurological diseases
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Publication Number
US-12246074-B2
Publication Date
2025-03-11
Expiration Date
Abstract
Gene therapy using expression vectors containing a granulocyte colony-stimulating factor (GCSF) gene are able to protect cells in a cell-based as well as animal-based models for ischemic stroke.
Core Innovation
The invention relates to GCSF gene therapy using a viral vector to reduce brain injury and improve neurological outcomes in mammalian subjects. For ischemic stroke, a method is disclosed in which a viral vector that comprises a recombinant adeno-associated virus (AAV) encoding human granulocyte colony stimulating factor (GCSF) is administered to the eye after cerebral ischemia/reperfusion injury.
The viral vector further comprises a neuron-specific promoter operatively linked with the GCSF gene and a hypoxia-sensitive gene switch/biosensor operatively linked with the GCSF gene. The hypoxia-sensitive gene switch/biosensor is described as being based on hypoxia response element (HRE) and hypoxia inducible factor (HIF) to drive preferential GCSF expression in hypoxic neurons.
For Alzheimer’s disease, the invention discloses a method of treating AD by administering to the eye a viral vector that encodes a GCSF gene in a mammalian subject having elevated levels of brain amyloid-β (Aβ) and neurological deficit caused by AD. The disclosed approach is associated with reported reductions in Aβ levels and with modulation of ER-stress and apoptosis markers, together with improved behavioral outcome consistent with neuroprotective effects.
Claims Coverage
Two independent claims are covered: one for stroke infarct-volume reduction and one for Alzheimer’s disease treatment. The inventive features comprise eye administration of a viral vector encoding GCSF, neuron-specific promoter control, hypoxia-sensitive gene switch/biosensor control, and the stated therapeutic outcomes.
Eye administration of neuron-specific, hypoxia-sensitive AAV-GCSF for stroke infarct-volume reduction
Administering to the eye of the subject a viral vector comprising a recombinant adeno-associated virus comprising a gene encoding human granulocyte colony stimulating factor (GCSF), a neuron-specific promoter operatively linked with the GCSF gene, and a hypoxia-sensitive gene switch/biosensor operatively linked with the GCSF gene, wherein the volume of a brain infarct developing as a result of cerebral ischemia/reperfusion injury is reduced.
Eye administration of a GCSF-encoding viral vector for treating Alzheimer's disease
Administering to the eye of the subject a viral vector that encodes a granulocyte colony stimulating factor (GCSF) gene to treat Alzheimer's disease in a mammalian subject having elevated levels of brain amyloid-β (Aβ) and neurological deficit caused by the AD.
The claim coverage centers on delivering GCSF via a viral vector administered to the eye. For stroke, the vector includes a neuron-specific promoter and a hypoxia-sensitive gene switch/biosensor linked to the GCSF gene, and the outcome is reduced brain infarct volume after cerebral ischemia/reperfusion injury. For Alzheimer’s disease, the claim covers treatment of AD by eye administration of a GCSF-encoding viral vector in subjects with elevated brain Aβ and neurological deficit.
Stated Advantages
Reduced volume of a brain infarct developing in response to cerebral ischemia/reperfusion injury as compared to a subject not treated with the viral vector.
Reduction in Aβ levels, modulation of ER-stress and apoptosis markers, and improved behavioral outcome consistent with neuroprotective effects.
Documented Applications
Reducing brain infarct volume and improving functional and biological readouts in ischemic stroke/cerebral ischemia/reperfusion injury.
Treating Alzheimer's disease in a mammalian subject having elevated levels of brain amyloid-β (Aβ) and neurological deficit caused by AD.
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