Viral Vectors For Treating Neurogenic Detrusor Overactivity
AssigneesAssistance Publique-Hopitaux de Paris, Universite De Versailles-St Quentin En Yvelines
InventorsFrançois GIULIANO, Alberto L. EPSTEIN, Olivier LE COZ, Alejandro ARANDA
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Abstract
The present invention provides a method and a pharmaceutical composition for the treatment of the NDO comprising the viral expression vector carrying a transcription cassette that harbors transgene(s) inhibiting/silencing neurotransmission or synaptic transmission of afferent neurons.
Claims17
1-18. (canceled)
A method of selectively silencing afferent neurons of the bladder in a patient in need thereof, the method comprising administering to the patient a herpes simplex virus (HSV) viral expression vector comprising at least:
- a) an afferent neuron-specific promoter selected from:
- a Calcitonin Gene Related Peptide (CGRP) promoter, a Substance P promoter, or a TRP gene family promoter;
- b) at least one transcription cassette comprising a nucleotide sequence operably linked to the promoter,
- wherein the nucleotide sequence prevents the neurotransmitter filled synaptic vesicles from attaching to the presynaptic membrane, therefore inhibiting exocytosis of the neurotransmitter from the presynaptic nerve terminal, and
- wherein the nucleotide sequence codes for a wild-type or a modified bacterial neurotoxin disrupting the SNARE complex or an active fragment thereof;
- and
- c) one sequence conferring long-term expression, wherein the long-term expression sequence is an LTE and a DNA insulator from the HSV-1 genome and wherein the transcription cassette is placed between the LTE and the DNA insulator.
Dependencies are inferred from the claim text.