Alzheimer’s disease is a chronic neurodegenerative disease that is the cause of 60–80% of cases of dementia. The most common symptom is difficulty remembering recent events. As the disease progresses, the symptoms worsen to include problems with language, disorientation, mood swings, loss of motivation, and behavioral issues. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years. In the latest stages of the disease, patients become fully dependent on caregivers, seriously impacting the quality of life of the patient and their families. There is no cure for Alzheimer’s disease. Currently approved drugs focus on improving cognitive function, behavior, and activities of daily living.
Alzheimer’s disease is characterized by a loss of neurons that secrete and bind a critical neurotransmitter, acetylcholine (ACh). Neurotransmitters are chemicals that allows signals to be transmitted between nerve cells and other cells, such as muscle.
In the brain, ACh effects learning, memory, and other cognitive functions and is produced and released from neurons, and binds to receptors on other neurons to transmit electrical signals. Decreased acetylcholine levels and loss of alpha-7 nicotinic receptors negatively impacts learning, memory, and function. Acetylcholine is naturally recycled by an enzyme called acetylcholine esterase (AChE). Blocking this enzyme with an acetylcholinesterase inhibitor (AChEI) increases the concentration of ACh available to neurons for the transmission of electrical signals.
Several AChEIs have been approved for use over the past 25 years and work by increasing the level of ACh. They havebeen shown to improve cognition and function in people with dementia of the Alzheimer's type. However, increasing levels of ACh in the peripheral nervous system, such as in the gastrointestinal tract, may result in overstimulation of local neurons resulting in unwanted side-effects. AChEIs are absorbed in the small intestine and are often associated with side-effects such as dizziness, headaches, nausea, vomiting, diarrhea, and loss of appetite. These side-effects often result in poor compliance and discontinuation of therapy.
Alpha Cognition is developing a prodrug of an approved AChEI, designed to significantly reduce the side-effects observed with the other acetylcholinesterase inhibitors.