The new technique uses CERE-110 as the gene therapy agent which carries the active part of the drug, the NGF gene. This human DNA strand codes for the NGF protein, a natural substance that exerts regeneration effects where neurons are degenerating, halting cell death and reverse cell atrophy, the hallmarks of Alzheimer's.
The new drug is being used by researchers at Rush as part of a Phase I study to evaluate its safety and tolerability using two different doses. Memory and cognitive function will also be assessed regularly during the two-year period of the study. Six to twelve subjects with mild to moderate Alzheimer's disease, based on the specific cognitive tests used to classify the disease stage, will be enrolled in the study.
While the NGF gene is a drug its method of delivery is not orally administered. Neurosurgery is required to precisely inject the drug into the nucleus basalis of Meynert on both sides of the brain. This procedure is not without its risks, having undergone modification in order to increase the potential benefit of NGF and decrease the side effects that included such as weight loss and pain.
Results from an earlier Phase I study at the University of California, San Diego reported no adverse effects form NGF detected in the subjects, an indication that the biological therapy was itself safe and well tolerated.
However the study warned apparent trends toward improvements in rate of cognitive decline and brain activity was to be interpreted with extreme caution. This study used genetically modified skin cells to deliver the NGF. Results from this study were presented at the American Academy of Neurology conference in Philadelphia this past April.
The study being conducted at Rush University uses a different means of delivering NGF to the brain and does not require a skin biopsy or the use of skin cells.
The drug is delivered via an AAV vector that carries the NGF gene. It has been used in several other gene transfer studies to deliver different genes to treat cancer, cystic fibrosis, and Parkinson's disease.
Dr. Zoe Arvanitakis, co-principal investigator of the study said: "The vector will transfer the gene for NGF only to the area of the brain where it is placed. The virus is common; most people have already been exposed to it and so have developed antibodies to the virus in their blood."
Currently, there are five Food and Drug Administration (FDA) approved medications for use in treating cognitive symptoms in patients with Alzheimer's disease. These are Namenda (menantine), Exelon (rivastigmine tartrate), Cognex (tacrine), Aricept (donepezil), Reminyl (galantamine).
All of them work by the same mechanism. The drugs increase the level in the brain of acetylcholine, a chemical that nerves use to communicate with each other. Alzheimer's sufferers are deficient in this neurotransmitter, and the drugs work by inhibiting an enzyme called cholinesterase that breaks down the acetylcholine.
These cholinesterase inhibitors have an effect on the symptoms, but none of the available drugs are known to change the underlying neurobiology of the disease. During treatment the nerve cells are known still be dying and the plaques and tangles are still forming.
Arvanitakis added: "If you can positively affect the basal forebrain, it may have a widespread effect on the entire brain because projections from that area reach out to all other parts of the brain, delivering the important neurotransmitter acetylcholine."
Alzheimer's disease is a neurodegenerative disease involving deterioration of the brain. Memory loss and the inability to perform daily activities are hallmarks of this fatal disease. Alzheimer's disease, the fourth leading cause of death behind cardiovascular disease, cancer and stroke, affects up to 4 million adults in the United States, and 10 million worldwide. It has an annual US price tag of approximately $100 billion (€81 billion) in direct (healthcare and related) and indirect (income) costs. It is estimated that delaying the onset of the disease by five years could save the nation's healthcare system as much as $50 billion.