Science at Ceregene
Repairing the Nervous System
At Ceregene, we are focused on developing products that use naturally occurring neurotrophic factors. Many different neurotrophic factors exist in the brain, with each having powerful biological effects on a select population of cells in the brain and eye. During development, they are essential for the normal growth of cells and the connections they must form with each other. During adulthood, most take on an important maintenance role for these same cells. Decades of research, in laboratories around the world, have demonstrated that when extra quantities are delivered to cells that are sick or dying, the appropriate neurotrophic factors restore the health and function of the cell while also protecting it from further damage and death. Several neurotrophic factors have been shown to have these powerful beneficial effects on cells whose death is responsible for the major symptoms of serious neurodegenerative and ocular diseases. Thus, if they could be effectively delivered to the affected region of the brain or eye of patients with serious neurodegenerative and ocular diseases, these neurotrophic factors should offer unprecedented benefits.
Past efforts to use these factors as therapeutics for human disease have failed, primarily because they pose enormous difficulties when trying to deliver them to the target tissues in a safe, effective and sustained manner. Indeed, most experts now acknowledge it is likely impossible to use conventional methods to deliver neurotrophic factors to targeted sites in the brain and eye for therapeutic purposes using conventional means (see Treatment Technology section below). Ceregene’s approach to treating these diseases with neurotrophic factors differs substantially from traditional therapeutic options. Current treatments are intended merely to provide short-term, symptomatic treatment for degenerative diseases of the brain and eye. They are not intended to significantly improve the vitality of the dying neurons nor therefore help protect them from further damage or alter the disease process. For each disease we are treating, we have selected a specific neurotrophic factor that is known to enhance function and vitality of the cells most affected by the disease. We then target the delivery of the gene for that neurotrophic factor directly to the major site where those cells are degenerating. Thus, our therapeutic approach not only offers the opportunity to reduce serious symptoms of these diseases, but also to halt or even reverse cellular degeneration, thereby normalizing function and slowing, halting or even reversing disease progression.
Treatment Technology: Overcoming Age-old Delivery Obstacles
Because neurotrophic factors are large proteins, they cannot be given orally nor can they even be injected intravenously for they do not have ready access to the brain or retina when administered using conventional drug delivery techniques. Moreover, in order to be effective as therapeutics for chronic human diseases, neurotrophic factors must be permanently present in the degenerating cells; otherwise, the cells will lose function and die. To overcome these problems and provide targeted treatment directed only to the affected cells, we have developed a gene delivery technology that provides the means to deliver the gene that encodes one of these neurotrophic factors. Thus, we deliver the genes for these proteins to the affected sites in the brain or eye, rather than attempting to deliver the proteins themselves. The gene for the neurotrophic factor thereafter resides in the affected cells, enabling these cells to produce the therapeutic neurotrophic factor indefinitely. Thus, Ceregene’s approach provides the opportunity to provide long-lasting, possibly permanent, treatment of the disease following a single dosing procedure. Because of these advantages, we feel that gene transfer, as developed by Ceregene, provides the best hope for truly effective symptomatic treatment and disease modification of these debilitating human diseases.
In order to implement our gene delivery technology for treating human diseases with neurotrophic factors, we developed gene delivery vectors to target the expression of neurotrophic factors genes to degenerating tissues. All of our current delivery vectors use a highly modified and apparently harmless version of adeno-associated virus (AAV). We anticipate that a single treatment of each vector should provide prolonged, perhaps permanent production of the therapeutic factor in the targeted cells. By switching the genes for different neurotrophic factors in the AAV vector system, we are able to build entirely different products for a wide range of different human diseases, including Parkinson’s Disease, Alzheimer’s Disease, ALS (Lou Gehrig’s Disease), Huntington’s Disease and several ocular diseases, such as retinitis pigmentosa, age-related macular degeneration and glaucoma.