| abstract |
The present invention features, inter alia, pharmaceutical compositions and their use in the preparation of a medicament (e.g., a medicament for inflammation, such as an inflammatory lung disease) or in a therapeutic regimen. The compositions can include at least two active agents: a first agent that inhibits PDE4 (e.g., roflumilast) and a second active agent that inhibits the expression or activity of one or more PDE4B variants (e.g., PDE4B2). The compositions and methods will attenuate an unwanted up-regulation of a PDE4B (e.g., PDE4B2) and may thereby improve treatment with the first agent (e.g., roflumilast). For example, the second agent may improve the efficacy of the first agent, decrease the effective dose of the first agent, ameliorate the tolerance to the first agent that would otherwise develop (e.g., in patients with COPD exacerbation), reduce unwanted side effects caused by the first agent, or otherwise improve treatment regimes including a PDE4 inhibitor. |