Italian gene discovery leads to atherosclerosis treatment trial
The identification of a genetic mutation in some Italian villagers has led to the first clinical trial of an agent to reduce atherosclerosis in acute coronary syndromes.
In 1980, Milan investigators found a family with low high-density lipoprotein
cholesterol levels but none of the expected signs of atherosclerotic
vascular disease. The discovery of their mutant apolipoprotein (apoA-I
Milano) led to a recombinant phospholipid complex that showed promising
results in animal studies.
In the first trial in humans, 123 patients with acute coronary syndromes
received weekly infusions of the complex or placebo for five weeks. Patients
treated with the complex had regression in atheroma volume compared with
baseline, with no change for those given placebo, as measured by intravascular
ultrasound (JAMA 2003;290:2292).
In an accompanying comment, Dr Daniel Rader, University of Pennsylvania,
suggests that patients with acute coronary syndromes may some day receive “acute
induction therapy” with HDL-based therapies for rapid regression
and stabilisation of lesions followed by long-term therapy to prevent
their regrowth (ibid, p2322). |
