Selected Medicines in Development for Alzheimer's

Current medicines for Alzheimer’s disease are approved to treat the symptoms of the disease – helping memory and thinking – but do not address the underlying causes of the disease. Current research is focused on treatments that may stop or slow disease progress – disease-modifiers. Two key hallmarks of Alzheimer’s disease are the appearance of amyloid plaques and neurofibrillary tangles. Plaques are comprised of aggregated amyloid-beta protein while tangles (that can damage or kill nerve cells) are made principally from aggregated tau protein, a microtubule-associated protein. Other areas of research are looking at how the role inflammation and insulin resistance play in Alzheimer’s disease.

Removing Plaque – A humanized monoclonal antibody in development is designed to remove beta amyloid protein from the brain and prevent or reverse progression of Alzheimer’s disease. The medicine provides the patient with antibodies (proteins involved in the body’s immune response), rather than the patient having to create their own immune response to beta amyloid. This process – called passive immunization – may provide greater reduction of safety concerns due to the lack of stimulation to the patient’s immune response to beta amyloid.

Preventing Plaque Formation – A potential medicine has been shown to prevent the formation and accumulation of beta-amyloid protein, leading to amyloid plaques. It may also target the tau protein, by inhibiting the protein from forming filaments that are important in neurofibrillary tangle formation. Both the amyloid plaques and tau tangles are important hallmarks of Alzheimer’s disease.

Intranasal Treatment – An intranasal peptide derived from a naturally occurring protein produced in the brain, called activity-dependent neuroprotective protein (ADNP), is in development for the treatment of amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer’s disease. The medicine is able to penetrate the blood-brain barrier, a filter that can prevent some substances from entering the brain and reaching its target. The medicine targets the tau protein, which under normal conditions binds to microtubules, stabilizing the structure and integrity of brain cells (neurons). Tangles occur as the result of the degeneration of microtubules, leading to cell dysfunction and cell.

Gene Therapy – A gene therapy for the treatment of Alzheimer's disease in clinical trials is designed to deliver nerve growth factor (NGF) to the brain. NGF is a naturally occurring protein that maintains the survival of nerve cells in the brain. The gene treatment is injected into the brain region where cholinergic cell degeneration occurs in Alzheimer’s disease. The cholinergic system is important in memory and cognitive function. It is thought that restoration of these functions may improve memory in Alzheimer’s patients and may have potential for long-lasting restoration due to sustained expression of NGF in the brain.

Vaccine Treatments – A synthetic vaccine in testing targets the amyloid-beta protein for the treatment of Alzheimer’s disease. The vaccines was developed using a proprietary affitope technology. Affitopes are peptide mimics designed to induce antibodies against a native antigen, without producing a systemic immune response. A second vaccine in development for the treatment of Alzheimer's disease uses a specific adjuvant that is expected to improve the vaccine by producing more potent and durable immune responses against certain Alzheimer’s disease antigens.

Helping Memory – A treatment in development selectively targets certain receptors in the brain associated with learning and memory, without system wide side effects. Currently available treatments approved for Alzheimer’s symptoms are not brain specific and can alter systems in the entire body, leading to possible negative side effects. In clinical trials, the new medicine showed statistically significant improvements in global function and cognitive function compared to placebo.

Diagnosing Alzheimer’s – Currently, a diagnosis of Alzheimer’s disease is based on cognitive testing, but the only definitive way to diagnose Alzheimer’s disease is by conducting a biopsy of the patient’s brain after death. There are several potential positron emission tomography (PET) imaging agents in clinical trials that hope to identify amyloid beta plaques in the brain early in Alzheimer’s disease.