A team of scientists from the German Center for Neurodegenerative Diseases (DZNE) and the Heilbrunn-Wolfgang Marien Alzheimer’s Research Center (HHKIRF) has succeeded in re-clarifying the relationship between a particular gene mutation and age-related macular degeneration (AMD), which can often be confusing for the patient.
In a study published in the journal Cell Reports, the scientists from the DZNE and Heilbrunn have shown that a particular genetic mutation of the anterior-ocular assembly (A-Ola) gene promotes the formation of abnormal blood-based macula in mice.
The authors expressed the function of the gene’s abnormal counterpart in the healthy eye in recipient mice via drug treatment. In a group of untreated mice, the scientists presented a limited progression-free condition in which they gave a drug treatment for six weeks. In order to study whether or not the treatment resulted in sufficient clinical improvement, they injected these untreated mice into a group of age-matched mice.
“Not only did the treatment result in the activation of a gene originally related to the development of macular degeneration, but also increased functional capacity of the blood cells present in the macula,” explains Dr. Timm Holzmann, directeur of the group’s studies. “This all indicates that the disease processes are influenced by the altered blood-based cells in the eye.”
The authors reported earlier that the genetic mutation in the A-Ola gene triggered via the gene’s abnormal function showed some molecular changes. Despite this, the scientists believed that the related gene mutation was the cause of the improvements found in their treated mice. As a result, they concluded that the genetic mutation triggered by the A-Ola gene mutation is indeed the cause of age-related macular degeneration. The new work reproduces that conclusion by a molecular level. “By examining the correct function of the gene mutated in the A-Ola in recipient mice, we have been able to confirm that it was indeed mutated during the development of the macula. Therefore, we conclude that the A-Ola gene is mutated during the development of the macula in recipient mice,” emphasises Holzmann.
New treatment strategy.
By applying the results of their study, it is possible to re-create a beneficial treatment that becomes available for the most severe patients. “The cure strategy presents a challenge, as the genetic mutation we have studied does not affect much. No longer we need to try to cure the disease, we instead need to control the disease. This is very complex but we are pursuing it on a molecular level and hope it will find its way to therapy for people with the dangerous condition,” says Holzmann.
As it is considered an extremely niche field, there are no approved medications for the treatment of age-related macular degeneration. Nevertheless, drugs are currently in development in the form of antibodies that target the mutated portions of the A-Ola gene. If the therapy is successful and proves to be efficacious, the individuals affected may still have to change their diet and lifestyle in the first place: “Though this approach is still in its earliest phases, it is already proving to be very successful. It is possible to reverse the degeneration and prevent blindness in the most serious situations,” says Holzmann.