Materials and Methods for p11-mediated Gene Therapy of Depression
- 詳細技術說明
- This invention providesvectors for increasing p11 expression in a mammal and also provides methods toincrease p11 expression for treating major depressive disorder or refractorydepression or improving responsiveness to treatment for major depressivedisorder or refractory depression.
- *Abstract
-
Serotonin is a keyneurotransmitter in depression-like states. p11, an S100 family protein, hasbeen discovered to be a key regulator of the serotonin receptor, 5-HT1B. p11knockout mice exhibit depression-like phenotypes.
To better understand the involvement of p11action in depressive states, Cornell researchers have focally altered p11expression in normal adult mouse brain using adeno-associated virus-mediatedgene transfer. They have identified the nucleus accumbens as a key site of p11action. Reduction of p11 in the nucleus accumbens of normal adult mice resultedin depression-like behaviors. Restoration of p11 expression in the nucleusaccumbens of p11 knockout mice normalized depression-like behaviors. Humannucleus accumbens tissue sampled from depressed patients after death also showsa significant reduction of p11 protein relative to similar samples from non-depressed,matched controls.
These results suggestthat p11 loss in nucleus accumbens may contribute to the pathophysiology ofdepression. Normalization of p11expression within nucleus accumbens may be of therapeutic value for majordepressive disorder or refractory depression.
This inventionprovides materials and methods for p11-mediated therapy of major depressivedisorder or refractory depression.
PotentialApplications
- Genetherapy for the treatment of major depressive disorder or refractory depression
- Therapyto improve responsiveness to treatment for major depressive disorder orrefractory depression
Advantages
- Couldprovide long term relief from major depressive disorder or refractorydepression
- Pinpoints area for administration
- *Licensing
- Dan-Oscar Antsonda429@cornell.edu212-746-1297
- 其他
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- Reversal of depressed behaviors in mice by p11 genetherapy in the nucleus accumbens. Sci. Transl Med,2010, 2, 54ra76.
- Issued US patent: Materials and methods for genemediated therapy of psychiatric disorders. US8642341 B2.
- 國家/地區
- 美國
