Backgrounder: Selected Medicines in Development for Alzheimer's

Selected Medicines in Development for Alzheimer's

Current medicines for Alzheimer’s disease are approved to treat the cognitive symptoms of the disease – helping memory loss, confusion and problems with thinking – but do not address the underlying causes of the disease.  Current research is focused on treatments that may stop or slow down the disease progression – disease-modifying agents. Two key hallmarks of Alzheimer’s disease are the appearance of amyloid plaques and neurofibrillary tangles in the brain. Plaques are abnormal clusters of beta-amyloid protein fragments between nerve cells, while tangles are twisted fibers made primarily of a protein called “tau” that accumulates in the brain cells, damaging and killing them. Other areas of research are looking at the role inflammation and insulin resistance play in Alzheimer’s disease.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 researchers hope will help with diagnosis by identifying beta-amyloid plaques in the brain early in Alzheimer’s disease.

Helping Memory – A treatment in development selectively targets 5HT6 receptors in the brain. These receptors are associated with learning and memory.  Currently available symptomatic treatments, such as cholinesterase inhibitors, are not brain specific and can alter systems in the entire body, leading to possible side effects.  A brain selective treatment like this has the potential to reduce systemic side effects.

Gene Therapy to Restore Neuronal Function – Agene 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 important for neuron survival.  The gene treatment is injected into the brain region where neuron degeneration occurs in Alzheimer’s disease. It is thought that the resulting sustained expression of NGF in the neurons can restore their lost functions, leading to memory and cognition improvement.

Neuroprotection with 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.  ADNP is essential for brain formation, and its loss leads to cognitive deficits and degeneration of the microtubules normally associated with the tau protein to maintain the integrity of brain cells (neurons).  This potential medicine appears to protect the microtubules from damage that would lead to tau protein tangle formation and neuronal dysfunction.  

Boosting Immune Responses with Vaccine Treatments – A synthetic vaccine using an “affitope,” a peptide designed to mimic beta-amyloid antigens, induces antibody production against this protein, without creating a systemic immune response (which carries safety concerns).  Another vaccine in development for the treatment of Alzheimer's disease uses a specific adjuvant (an immunological agent able to modify the effect of another agent) to enhance the vaccines effectiveness by producing a more potent and sustained immune response against certain beta-amyloid antigens.

Preventing Plaque Formation – A small molecule compound that has been shown to reduce the formation, deposition and accumulation of beta-amyloid protein, as well as induce its removal from already formed plaques. It also appears to target the tau protein, by inhibiting the protein from forming filaments that are important in neurofibrillary tangle formation. It potentially could affect both of the two major known components of Alzheimer’s disease brain lesions.

* From Medicines in Development for Alzheimer’s Disease, PhRMA, 2012

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