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Drug intelligence / Profile preview
Ad-D4
- Development stage
- Preclinical
- Lead developer
- University of Naples Federico II
- Modality
- Gene Therapies
- Administration
- Intravenous
01
Overview
Ad-D4 is an experimental recombinant adenoviral gene therapy vector containing the human cDNA for the C-terminal D4 domain of phospholipase D1 (PLD1). It is designed to overexpress the D4 domain in skeletal muscle, where it acts as a competitive inhibitor to disrupt the interaction between phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (PED/PEA-15) and endogenous PLD1. In type 2 diabetes, overexpression of PED/PEA-15 stabilizes PLD1, leading to constitutive activation of protein kinase C alpha (PKCα) and subsequent inhibition of insulin-induced protein kinase C zeta (PKCζ) activation, which impairs glucose uptake. By disrupting the PED/PEA-15/PLD1 complex, Ad-D4 reduces PKCα activity, restores PKCζ activation, and rescues insulin sensitivity and glucose tolerance. Ad-D4 has been investigated in preclinical models of type 2 diabetes and obesity.
- Other names
- Ad-PLD1-D4Ad-PLD-1-D4Ad-PLD 1-D4adenoviral PLD1-D4recombinant adenoviral vector containing the human D4 cDNA
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