RGD Reference Report - Long-term gene therapy in the CNS: reversal of hypothalamic diabetes insipidus in the Brattleboro rat by using an adenovirus expressing arginine vasopressin.

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Long-term gene therapy in the CNS: reversal of hypothalamic diabetes insipidus in the Brattleboro rat by using an adenovirus expressing arginine vasopressin.
Authors:	Geddes, B J Harding, T C Lightman, S L Uney, J B
Citation:	Geddes BJ, etal., Nat Med. 1997 Dec;3(12):1402-4. doi: 10.1038/nm1297-1402.
RGD ID:	150429657
Pubmed:	PMID:9396613 (View Abstract at PubMed)
DOI:	DOI:10.1038/nm1297-1402 (Journal Full-text)
The ability of adenovirus (Ad) to transfect most cell types efficiently has already resulted in human gene therapy trials involving the systemic administration of adenoviral constructs. However, because of the complexity of brain function and the difficulty in noninvasively monitoring alterations in neuronal gene expression, the potential of Ad gene therapy strategies for treating disorders of the CNS has been difficult to assess. In the present study, we have used an Ad encoding the arginine vasopressin cDNA (AdAVP) in an AVP-deficient animal model of diabetes insipidus (the Brattleboro rat), which allowed us to monitor chronically the success of the gene therapy treatment by noninvasive assays. Injection of AdAVP into the supraoptic nuclei (SON) of the hypothalamus resulted in expression of AVP in magnocellular neurons. This was accompanied by reduced daily water intake and urine volume, as well as increased urine osmolality lasting 4 months. These data show that a single gene defect leading to a neurological disorder can be corrected with an adenovirus-based strategy. This study highlights the potential of using Ad gene therapy for the long-term treatment of disorders of the CNS.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
AVP	Human	diabetes insipidus	treatment	ISO	Avp (Rattus norvegicus)		RGD
Avp	Rat	diabetes insipidus	treatment	IMP			RGD
Avp	Mouse	diabetes insipidus	treatment	ISO	Avp (Rattus norvegicus)		RGD
Avp^di	Rat	diabetes insipidus	treatment	IMP			RGD
BRAT-Avp^di/BluHsd	Rat	diabetes insipidus	treatment	IMP			RGD

Objects Annotated

Genes (Rattus norvegicus)

Avp (arginine vasopressin)

Avp^di (arginine vasopressin; diabetes insipidus mutant)

Genes (Mus musculus)

Avp (arginine vasopressin)

Genes (Homo sapiens)

AVP (arginine vasopressin)

Strains

BRAT-Avp^di/BluHsd (Brattleboro)

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Long-term gene therapy in the CNS: reversal of hypothalamic diabetes insipidus in the Brattleboro rat by using an adenovirus expressing arginine vasopressin.