Gene Therapy to Treat Aortic Aneurysms

been well described. This is a disease primarily of older adults, with white men much more likely to harbor an AAA than are black women. Other risk factors for developing an AAA include cigarette smoking, hypertension, chronic ob- structive pulmonary disease, and a family history of aortic aneurysms. Atherosclerosis in other vascular beds also puts the patient at increased risk for the development of an aortic aneurysm. See p 1008 During the past 20 years, an explosion of information on the pathogenesis of aortic aneurysms has been generated.3,4 Much of this basic science work has been descriptive and performed by surgeons, who are the primary managers of the treatment of patients with AAAs. This occurred at least partially because there is no proven medical therapy to inhibit aortic aneurysms from forming or slowing their growth once a small AAA has been recognized. Therefore, the manage- ment of AAAs is surgical, with intervention occurring once the risk of aortic rupture exceeds the risk of elective repair. There are 2 surgical options for patients with an AAA once their aneurysm has attained a certain diameter based on 2 large randomized trials.5,6 Open surgical repair has been established for 50 years and is a curative procedure. This cure comes with an increased short-term morbidity and mortality as compared with the less-invasive option of endo- vascular repair. Endovascular AAA repair, although associ- ated with lower morbidity and mortality as compared with open AAA repair,7 converts the AAA into a chronic condition that needs to be followed expectantly with serial CT scans. Reintervention is required if the AAA continues to enlarge or if the endograft structurally deteriorates. Ongoing trials8,9 in the United States and Europe will determine whether endo- vascular therapy should be the primary therapy offered to patients once their AAA reaches a threshold diameter. Unfortunately, this leaves a large cadre of patients (10% of men older than age 65 may harbor an AAA) without any good medical options to treat their AAA. Clearly, smoking cessa- tion is indicated, but rarely successful. In addition, although -blockers have been touted in animal studies as being capable of slowing AAA growth,10 the best study to date in humans with AAAs failed to show a significant reduction in AAA growth rates as compared with placebo.11 Pharmacological therapy using doxycycline, a nonselective matrix metalloproteinase inhibitor, has been the most well- studied compound in the treatment of AAAs. In rodents, systemic12 and periaortic13 application of doxycycline inhibits AAA growth. Studies in humans also suggest that doxycy- cline may slow AAA growth.14