Age-Related Eye Disease Study (AREDS) and Age-related Eye Diseases Study-2 (AREDS-2) were landmark studies in providing a clue to show benefit from nutritional supplements. The article below, from Retina India's newsletter from 2013, is still relevant today to patients of Age-related macular degeneration.
Retina India is a not-for-profit organization, registered with the Charity Commissioner, Mumbai, India, established for empowering people with retinal disorders, and bringing them and their families on a common platform with physicians, researchers, counselors, low vision and mobility experts and other specialists.
Showing posts with label dry AMD. Show all posts
Showing posts with label dry AMD. Show all posts
Thursday, January 22, 2015
Saturday, April 27, 2013
Phase 2b/3 clinical trial of Emixustat Hydrochloride in subjects with geographic atrophy associated with dry Age-related Macular Degeneration
Acucela Inc., a clinical-stage biotechnology company focused on developing new treatments for sight threatening eye diseases, announced phase 2b/3 clinical trial investigating emixustat hydrochloride in subjects with geographic atrophy (GA) associated with dry age-related macular degeneration (AMD) has been initiated.
AMD is the most common cause of irreversible vision loss in the developed world, the overwhelming majority of which is associated with dry AMD. There are currently no medications approved to treat GA associated with dry AMD. Emixustat hydrochloride is being studied to determine whether it slows the progression of GA in patients with GA associated with dry AMD.
The SEATTLE study (for Safety and Efficacy Assessment Treatment Trials of Emixustat Hydrochloride) was initiated based on data from the recently completed phase 2a study, the results of which will be announced at the ARVO 2013 Annual Meeting, as well as feedback from the U.S. Food and Drug Administration (FDA).
Emixustat hydrochloride has a unique mechanism of action in visual cycle modulation, offers oral dosing and the ability to specifically target the visual cycle, representing a potentially novel therapeutic approach for the treatment of retinal diseases, such as GA associated with dry AMD.
The SEATTLE study of emixustat hydrochloride is designed as a phase 2b/3 multicenter, randomized, double-masked, dose-ranging study comparing the efficacy and safety of emixustat hydrochloride with placebo for the treatment of geographic atrophy (GA) associated with dry age-related macular degeneration (AMD). Approximately 440 patients with GA associated with dry AMD will be enrolled in the study across 56 sites, primarily in the United States.
There are more than 10 million people in the US and more than 120 million people worldwide who have age-related macular degeneration. AMD is associated with irreversible vision loss, the overwhelming majority of which is due to the dry form of AMD, representing approximately 90% of all cases. Dry AMD occurs when the light-sensitive cells in the back of the eye slowly deteriorate, gradually blurring the central field of vision. As the disease advances, and where patients typically present with GA, the blurred vision slowly progresses to blindness in affected areas of the eye.
Thursday, May 19, 2011
Possible new treatment for Macular Degeneration
Researchers from University of Kentucky College of Medicine have identified an RNA-based mechanism in the retina that could be responsible for triggering the blindness associated with advanced dry age-related macular degeneration (AMD). The article has been published in Nature.
Unlike wet AMD, which results from scarring caused by leaky blood vessels and thus can be treated with a variety of angiogenesis inhibitors, dry AMD is initially characterized by the buildup of extracellular debris beneath the retina. Over time, those deposits cause significant atrophy of the retinal pigment epithelial (RPE) layer—a condition known as geographic atrophy—leading to loss of photoreceptors in the macula, the central and the most important part of the retina, which can ultimately advance to permanent blindness.
Although difficult to predict, dry AMD can turn into wet AMD at any time during disease progression. There are no medical or surgical treatments for dry AMD.
To find potential targets for geographic atrophy, Dr Jayakrishna Ambati and colleagues initially looked at levels of proteins and nucleic acids in eye samples from dry AMD patients. The researchers found that levels of the microRNA-processing enzyme dicer 1 ribonuclease type III (DICER1) were significantly lower in patient eyes than in non-AMD control eyes (p=0.0036). DICER1 levels were unchanged in the RPE layer of human eyes with other retinal diseases, suggesting that low DICER1 could be a specific marker of geographic atrophy.
The team next generated Dicer1 knockout mice to recapitulate the geographic atrophy phenotype in animals. All the Dicer1 knockouts showed degeneration of the RPE layer compared with wild-type littermate controls.
Subsequent studies in human RPE cells and mice revealed the specific mechanism by which low DICER1 levels led to degeneration of the RPE cells or layer, respectively. The decrease in DICER1 caused the accumulation of cytotoxic Alu RNA molecules in the RPE layer, where they caused degeneration of tissues making up the retina and macula.
Alu RNAs are retrotransposon sequences that exist throughout the human genome but do not code for proteins. Considered to be a toxic type of RNA that play a disease-causing role in a large section of the human genome, these Alu-related elements make up 11 percent of the human genome. They were considered "junk" DNA because researchers did not understand their role, but are now considered to play a crucial role in the death of retinal cells in those with geographic atrophy
In cultured human RPE cells with low DICER1 levels, antisense oligonucleotides targeting Alu RNA significantly blocked RPE cellular degeneration compared with control oligonucleotides (p<0.05).
Simply said, in patients with geographic atrophy, reduction of the Dicer enzyme in the retina leads to accumulation of Alu RNA, which leads to death of the retina.
The team has also developed two therapies that may prevent geographic atrophy. The first therapy increases Dicer levels in the retina by "over-expressing the enzyme", while the second therapy blocks Alu RNA with a drug that clings to the toxic structure and degrades it. Based on experiments performed in the laboratory, both therapies could efficiently prevent geographic atrophy.
The University of Kentucky has filed for patents on both therapies, and clinical trials are expected to begin by the end of this year.
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