New Therapeutic Approach for Treatment of Age-Related Macular Degeneration

The scientists discovered that the inhibition of Runt-bound transcription factor 1 (RUNX1), which has been linked to retinal neovascularization and the development of abnormal blood vessels leading to vision loss, presents a new therapy approach to treat age-related macular degeneration (AMD). Their results are published in the American Journal of Pathology.

Abnormal growth of blood vessels, or aberrant angiogenesis, originates from the choroid, a portion of the eye behind the retina. This condition, known as choroidal neovascularization (CNV), is present in many eye diseases that lead to blindness like AMD. This study is the first to include RUNX1 in CNV and to test RUNX1 inhibition therapy for the treatment of CNV. The researchers found that the application of a RUNX1 inhibitor alone or in combination with standard therapy for AMD may represent a significant therapeutic advance.

The incomplete response to anti-vascular drugs with endothelial growth factor (VEGF) is a critical problem that impairs the visual outcomes of CNV. RUNX1 is a promising therapeutic target that can help address the current limits of GEF therapy," Explains the first author Lucia Gonzalez-Buendia, M.D., retinal specialist at the Puerta de Hierro-Majadahonda University Hospital (Spain), former Post-Doctorate at the Schepens Eye Research Institute of Mass Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.

The research team induced CNV lesions in mice. Immediately thereafter, the mice received a single intravitreal injection of saline, aflibercept (a Food and Drug Administration-approved treatment for VEGF), the RUNX1 inhibitor Ro5-3335, or a combination of Ro5-3335 and aflibercept. A single intravitreal injection of Ro5-3335 by itself significantly reduced the size of the CNV lesion seven days after induction of the CNV lesions. The combination of Ro5-3335 and aflibercept reduced vascular leakage more effectively than aflibercept alone.

RUNX1 inhibitors are very promising to complement or replace anti-VEGF treatments in patients where anti-VEGF treatment is no longer effective, and with the possibility of being administered on a topical basis, it could be transformative in the field," suggests co-lead investigator Joseph F. Arboleda-Velasquez, MD, PhD, Assistant Scientist, Schepens Eye Research Institute of Mass Eye and Ear, and Assistant Professor of Ophthalmology, Harvard Medical School, Boston, MA, USA.

RUNX1 has been detected in all types of studied cells that are known to be implicated in CNV pathogenesis, suggesting that inhibiting RUNX1 can target not just angiogenesis, but also other important processes in the pathogenicity of CNV, such as inflammation and fibrosis. It can impact a wide variety of eye diseases, including AMD, diabetic retinopathy, prematurity retinopathy, retinopathy of the retinal vein, and other eye diseases.

"Demonstrating the potential for RUNX1 inhibition for CNV treatment beyond anti-VEGF treatment presents a unique approach to treating age-related macular degeneration.

and suggests the significance of future studies to test its effectiveness in patients," conclude co-lead researcher Leo A. Kim, MD, PhD, Associate Scientist, Schepens Eye Research Institute of Mass Eye and Ear, and Adjunct Professor of Ophthalmology, Harvard Medical School, Boston, MA, USA.

Did you know that the current treatment for AMD is invasive and loses efficacy over time. Patients of age related macualr degeneration are given multiple injections of anti-VEGF drugs into the eye. Around half of all patients report persistent retinal fluid arising from leaky blood vessels despite chronic treatment, which carries a substantial burden on those patients and on the health care system.

Source: If you wish to read the academic paper, please click here. 

Location: United States

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