AMD Treatment: Apolipoprotein A-I Reverses Resistance to Anti-VEGF Injections

A new study by Baylor College of Medicine shows that the addition of a protein to the treatment normally given to patients with choroidal neovascularization could reverse resistance to Anti-VEGF Injections.

Age-related Macular Degeneration

Age-related Macular Degeneration

Age-related macular degeneration (AMD) affects millions of people in the US. Some of them find themselves in a therapeutic impasse where their treatments do not work anymore. Researchers at Baylor College of Medicine have found a way to combat this resistance to therapy. They published their results in the medical journal Communications Biology.

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Treatment resistance a big problem

In exudative AMD, also known as wet AMD, choroidal neovascularization may occur which can lead to irreversible loss of vision. Doctors usually suggest that patients take anti-VEGF therapy, which is administered via injections. About a quarter of patients do not respond to the treatment, and about a third become resistant to it after several administrations, as the drug loses its effectiveness.

Adding a protein reverses resistance to the treatment

In mice, researchers have discovered that the administration of a protein, apolipoprotein A-I, in addition to anti-VEGF fights resistance to therapy and ensures its effectiveness. They built on previous research on anti-VEGF resistance which suggested that macrophages, could be associated with this resistance and that the accumulation of cholesterol in these cells was involved in the development of choroidal neovascularization. Several medical studies have found that the administration of apolipoprotein A-I lowers cholesterol levels in macrophages and endothelial cells, both involved in choroidal neovascularization. “All these observations suggest that apolipoprotein A-I can help combat anti-VEGF resistance and suppress choroidal neovascularization,” said the researcher.

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More and more people are affected

With their team, they tested their hypothesis on mice of different ages. They found that in older rodents the combination of the two treatments reduced choroidal neovascularization by 47%. In their opinion, the accumulation of cholesterol in macrophages is strongly associated with resistance to therapy. “Our results encourage us to test the combination of apolipoprotein A-I and anti-VEGF in clinical trials to see if it can help patients. “According to the investigator, AMD is expected to affect more and more people in the future. These new findings could change the way they are managed.

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Combination of apolipoprotein-A-I/apolipoprotein-A-I binding protein and anti-VEGF treatment overcomes anti-VEGF resistance in choroidal neovascularization in mice

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