A Guide to Research in Dry AMDCompiled by Dan RobertsUpdated February 4, 2010 This is a guide to all leading research to date in the field of dry age-related macular degeneration (AMD). It is divided into three categories: Pharmaceutical Gene Therapy Surgical Intervention All headings contain links to further information, which will open in new windows. Hopefully, this document will help to identify information of interest specifically to those who are still, and hope to remain, in the early and intermediate stages of AMD. PHARMACEUTICAL Phototrop (a combination of compounds which affect mitochondrial lipid metabolism) is now available in the United States. In the year-long study ending in May 2005, of 106 patients with early AMD, improvement was noted in visual field mean defect (VFMD), visual acuity, foveal sensitivity, and fundus alterations. In addition, in the treated group only 1 out of 48 cases (2%) showed worsening of VFMD, while in the placebo group 9 out of 53 (17%) showed worsening in VFMD. There was also a significant decrease in drusen-covered area of the treated eyes. More about Phototrop. POT-4 Potentia Pharmaceuticals, Inc. announced on March 20, 2007 that it was entering the clinical phase of development of POT-4 for treatment of age-related macular degeneration (AMD). According to the researchers, POT-4, a synthetic peptide, shuts down the complement activation system that can lead to local inflammation, tissue damage (as in dry AMD) and the resulting blood vessel growth (angiogenesis in wet AMD). Discovered by Professor John Lambris, University of Pennsylvania, POT-4 is the first complement inhibitor tested in patients with AMD. More about POT-4. Retinylamine In the October 2008 Journal of Biological Chemistry, researchers at the Case Western Reserve University School of Medicine reported on a new study in mice showing that retinylamine markedly slows the progression of AMD. The study, led by Akiko Maeda, provides insight into the biochemical trigger for genetic changes leading to the disease. Zinthionein Zinc has been shown to be an effective antioxidant, which is beneficial to the retina. In July 2008, researchers at Pipex Pharmaceuticals announced success with a complex that evidently results in a more potent antioxidant than zinc alone. This "zinc-monocysteine" molecule was developed by combining L-cysteine and zinc in a ratio of 1:1. Under the commercial name Zinthionein, it was then administered as a 25 mg oral capsule twice a day to 80 test subjects for a period of six months. According to the phase 2 study results (David Newsome, primary investigator), these patients demonstrated a highly statistically significant improvement in visual acuity, contrast sensitivity and photorecovery time. Continued success in the trials could lead to a new and effective therapy for dry AMD. More about Zinthionein. << Return to Top GENE THERAPY CD36 CD36 is a protein molecule (called an "integral membrane protein") permanently attached to the surface of certain human cells. It plays a role in the inflammation process, but researchers have now discovered that a deficiency of the protein may cause the dry form of macular degeneration. More about CD36. CFH and CFB Two genes have been shown to lead to age-related macular degeneration (AMD) in simultaneous studies. Called Complement Factor H (CFH) a potential cause of AMD in as many as 50% of cases, helps to control the body's immune response and inflammation. CFH stops the immune response, while Factor B activates it. More about CFH and CFB. CRP Levels C-reactive protein (CRP) levels in test subjects have displayed significant association with the presence of both intermediate and advanced stages of ARMD. More about CRP levels. C3 Researchers have found that a variant of the C3 gene can more than double the risk of age-related macular degeneration (AMD). More about C3. Fibulin 5 A July 22, 2004 report announced that Fibulin 5 was the second gene to have been shown to be related to AMD (the first being HEMICENTIN-1 in 2003). More about Fibulin 5. Hemicentin-1 The first gene mutation found (2003) to be directly tied to AMD. More about Hemicentin-1. Interleukin-6 and Interleukin-8 Two different studies during 2008 reveal that at least some cases of age-related macular degeneration may stem from genetically driven production of inflammatory cytokines called interleukin-6 and interleukin-8.More about interleukin-6 and interleukin-8. LOC387115 An April 2007 study showed that common variants of CFH (above) and another gene, LOC387115, independently increased the risk of progression from early or intermediate stages to advanced stages of AMD. More about LOC387115. RDH5 Japanese researchers reported in September 2003 that mutations in the RDH5 gene can cause macular dystrophy, fundus albipunctatus, and/or night blindness. More about RDH5. RPGR An article published in August 2002 reported that the gene RPGR (associated until now with retinitis pigmentosa) is also been found to be responsible for an X-linked form of early-onset MD. More about RPGR. Serping1 In October 2008, British scientists announced discovery of six variants within the gene, Serping1, that are associated with dry AMD. The report was published by Sarah Ennis and Andrew Lotery in the Lancet journal of the University of Southampton. TLR3 As reported in the Aug. 28, 2008 online edition of the New England Journal of Medicine, researchers have found a genetic link associated with dry AMD. That's the good news. The bad news is that siRNA drug therapy may increase the risk for dry AMD in patients who have that genetic variant. The research team found that the protein TLR3 helps fend off certain viral infections. However, it also increases the risk for dry AMD in subjects taking an experimental anti-VEGF drug called "small interference ribonucleic acid" (siRNA), which activates TLR3. In fending off viral infections, TLR3 also attacks infected retinal cells, resulting in "a 60 percent spike in retinal cell death among mice and humans genetically susceptible to developing dry AMD." Patients currently involved in the siRNA study (labeled Cand5) sponsored by Acuity Pharmaceuticals should contact their doctors for more information. << Return to Top SURGICAL INTERVENTION Retinal Stem Cells from Bone Marrow An April 2006 study reported early improvement in the vision of patients who received injections into the cornea of stem cells derived from bone marrow. More about stem cell transplantation in mice. Retinal Transplantation Since 2000, a team of doctors led by Norman D. Radtke, M.D. (University of Louisville) have been transplanting intact sheets of both immature (fetal) neural retina cells and retinal pigment epithelial (RPE) cells in the sub-retinal space of patients with dry AMD and other retinal dystrophies. More about retinal transplantation. Stem Cells from Human Embryos Advanced Cell Technology announced on September 23, 2004 that they had engineered human embryonic stem cells which could be used to repair a damaged retina. More about embryonic stem cell research. Stem Cells from the Iris A December 2001 article reported that, with manipulation of the CRX gene, cells from the iris may be able to replace photoreceptor cells in the retina. More about stem cells from the iris. Stem Cell Transplantation in Mice Scientists reported in November 2004 that they have improved the vision of mice with transplanted stem cells. More about stem cell transplantation in mice. Summary of Stem Cell Research The First Seven Years: An Overview of Stem Cell Transplantation Research for Treatment of Retinal Disease << Return to Top MD Support Home Page |