Therapies targeting the alveoli

Alveoli represent the primary site for gas exchange within the lung, and thus their health is vital for survival. Alveolar conditions with a primary genetic cause, such as surfactant protein-B (SP-B) deficiency and SP-C deficiency, are prime candidates for a rAAV-gene therapy approach. Diseases in which alveoli are damaged secondary to other defects might also be treated with gene transfer. Such conditions include environmental toxin exposure, infectious diseases, and adult respiratory distress syndrome (ARDS) (Table 4.1) (Rolls et al., 1997, 1998, 2001 Cheers et al 1999 Ruan et al., 2002). 

Early reports with rAd vectors may provide the proof of principle for transient expression of a number of potentially therapeutic proteins. For instance the Na+/K+-ATPase was found to promote reabsorption of alveolar fluid in an ARDS model (Factor et al., 1999 Sartori and Matthay, 2002). Anti-inflammatory cytokines and antioxidants have also been used with some success in a similar context in animal models of sepsis and ARDS (Van Laethem et al., 1998 Dumasius et al., 2002). 

ADENO-ASSOCIATED VIRAL VECTORS FOR GENE THERAPY 

Gene therapy targets from the alveolar compartment 

Alpha-1 antitrypsin deficiency Adult respiratory distress syndrome (ARDS) Pneumocystis pneumonia 

---