Alzheimer’s disease is a progressive brain disease. Early symptoms may include forgetfulness, apathy and depression, but late stages include an inability to communicate, care for oneself, walk or even swallow, and the disease is eventually fatal. An estimated 5.2 million Americans have Alzheimer’s, including 5 million over the age of 65. Alzheimer’s disease reduces the function of brain cells and the connections (called synapses) between them. Scientists think the accumulation of a protein called beta-amyloid and of an abnormal form of the protein tau contributes to this loss of function. Gradually, the transfer of information across the synapses begins to fail, the number of synapses declines and brain cells die. Alzheimer’s disease has no cure and no effective treatments. These scientists are developing a treatment for Alzheimer’s that acts by reducing the production of amyloid proteins in the brain.
More than 5 million Americans now have Alzheimer’s disease (AD), the sixth leading cause of death in the United States, and no disease-modifying drug is available. Edunn Biotechnology is a start-up company focused on development of antisense drugs for CNS indications. We request program assistance to carry out specific tasks for pre-clinical development of EDN-OL1 to support submission of an Investigational New Drug (IND) application to enable clinical trials for the Alzheimer’s indication, ultimately leading to FDA approval for treatment of AD patients. EDN-OL1, a patented antisense phosphorothioate oligonucleotide, crosses the blood-brain barrier after intravenous dosing and reduces production of amyloid precursor protein (APP) and, consequently, amyloid proteins in the brains of mouse models of AD. Edunn’s endpoint for EDN-OL1 efficacy in animal models has been to halt decline of cognitive function. In the three murine models tested, EDN-OL1 actually has restored cognitive function. The clinical benefit to AD patients may best be anticipated as a decrease in the rate of cognitive decline. We expect that patients would be maintained on one to four doses per month. EDN-OL1 efficacy does not require that any variety of late-onset AD arise from over-expression of APP because whatever the detailed ultimate pathology is, amyloid proteins are involved. Edunn plans separate development of an indication to treat CNS symptoms that result from the overexpression of APP that occurs in Down syndrome.
Pre-clinical development includes the manufacture and animal safety testing of the active pharmaceutical ingredient. Edunn proposes to use program resources to complete selected pre-clinical development tasks required for submission of an IND.
Edunn Biotechnology, St. Louis
Thomas Darling, Ph.D.
Public Health Impact
Alzheimer’s disease takes a large economic and quality-of-life toll not only on patients but also on caregivers and society as a whole. The disease is the most important dementia of the aged, with characteristic senile plaques, loss of synapses and the presence of neurofibrillary tangles. However, no drugs on the market successfully halt or reverse the symptoms of Alzheimer’s disease.
The BrIDGs scientists completed an extensive chemistry, manufacturing and controls campaign for the active pharmaceutical ingredient. During conduct of the project, the business strategy of Edunn Biotechnology changed, and the collaboration was concluded.
- Synthesis of Good Manufacturing Practice (GMP) and non-GMP material
- Formulation development