June is Alzheimer's & Brain Awareness Month. Today, we will unpack the reasons behind the difficulty of finding a cure for the condition and overview some of the current clinical trials of Alzheimer's.
Alzheimer's disease is not to be confused with dementia- a broad umbrella term used to describe a range of progressive neurological disorders. So dementia is not a single disease; it's a term that covers several conditions, including Alzheimer's disease. Alzheimer's disease is the most common cause of dementia as it accounts for around 6/10 of memory problem conditions.
Currently, there are no cures for dementia, but there are options to slow down the progression of the disease so the patients maintain their independence for longer. Four drugs are approved and currently used in symptomatic treatment for Alzheimer's; donepezil 1997, rivastigmine 2000, galantamine 2001, and memantine 2003. The problem with finding how to treat and prevent Alzheimer's disease lies in the conflicting theories of Alzheimer's causes. The current lack of understanding of the pathogenesis of the disease has restricted the development of effective treatments. A wealth of research data supports the amyloid hypothesis, which states that increasing levels of aggregated beta-amyloid proteins trigger the disease progression. Clinical trials arising from the Aβ hypothesis target causal steps in the pathway to reduce the formation of Aβ proteins or enhance their clearance. However, findings from these Alzheimer's clinical trials have failed to get us closer to developing therapeutics for central nervous system disorders. Consistent trial failures could be caused by issues with the methods commonly used in Alzheimer's disease clinical trials. Loss of subjects, life events and lack of specificity during diagnostic evaluations undermine the clinical trials. What's more, the Aβ proteins are routinely found in autopsies of elderly patients who did not exhibit any symptoms of dementia.
A different theory suggests that Alzheimer's is caused by the neuroinflammation caused by traumatic brain injury, spinal cord injury, stress, ageing, and infection. Drugs addressing this theory would be different from the ones targeting Aβ proteins but are still in the early stages of clinical development. Inhibition of brain inflammation could be accomplished with natural molecules, especially the polyphenoic flavonoids found in foods like apples, onions, dark chocolate, and red cabbage.
Despite the massive investment in Alzheimer's disease research, clinical trials for dozens of drugs are failing. Recent research suggests that additional pathogenic mechanisms of Alzheimer's might play a role in finding the pharmacological management of the cognitive and behavioural symptoms of the disease.
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