Thursday, May 15, 2014
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DNA-damage-inducible transcript 4 (DDIT4;
Rodent and human studies
suggest inhibiting REDD1 could help treat major depressive disorder (MDD). In
postmortem human prefrontal cortex samples from patients with MDD, mRNA
expression of the mammalian
target of rapamycin complex 1 (mTORC1)
inhibitor REDD1 was increased compared with that in samples from individuals
without MDD. Redd1 knockout mice showed resistance to chronic stress-induced
behaviors and decreases in mTORC1 signaling and the number and function of
spine synapses compared with wild-type mice. In rats, injection of a REDD1-expressing
viral vector into the prefrontal cortex induced behaviors and neuronal
atrophy similar to those caused by chronic stress. Next steps include
screening for compounds that disrupt the effect of REDD1.
RiboQuark Pharmaceutical Technology Co. Ltd. and Pfizer
Inc. have PF-655,
an siRNA targeting REDD1, in Phase II testing to treat diabetic macular edema
(DME) and wet age-related macular degeneration (AMD).
Published online May 15, 2014
Unpatented; unavailable for
Ota, K.T. et al. Nat.
Med.; published online April 13, 2014;
Contact: Ronald S. Duman, Yale School of Medicine, New
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