Q43:What unique qualities should a new drug for the treatment of Alzheimer’s disease possess in order to become successful?
Alzheimer-type dementia is a degenerative process, with a loss of cells from the basal forebrain, cerebral cortex, and other brain areas.
Causes: Three major competing hypotheses exist to explain the cause of the disease. The oldest, on which most currently available drug therapies are based, is the cholinergic hypothesis, which proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine. The cholinergic hypothesis has not maintained widespread support, largely because medications intended to treat acetylcholine deficiency have not been very effective. Other cholinergic effects have also been proposed, for example, initiation of large-scale aggregation of amyloid, leading to generalised neuroinflammation.
In 1991, the amyloid hypothesis postulates that amyloid beta (Aβ) deposits are the fundamental cause of the disease. It is a compelling theory because the gene for the amyloid beta precursor (APP) is located on chromosome 21, and people with trisomy 21 (Down Syndrome) who thus have an extra gene copy almost universally exhibit AD by 40 years of age. Also APOE4, the major genetic risk factor for AD, leads to excess amyloid buildup in the brain before AD symptoms arise. Thus, Aβ deposition precedes clinical AD. Further evidence comes from the finding that transgenic mice that express a mutant form of the human APP gene develop fibrillar amyloid plaques and Alzheimer’s-like brain pathology.An experimental vaccine was found to clear the amyloid plaques in early human trials, but it did not have any significant effect on dementia.
Deposition of amyloid plaques does not correlate well with neuron loss. This observation supports the tau hypothesis, the idea that tau protein abnormalities initiate the disease cascade. In this model, hyperphosphorylated tau begins to pair with other threads of tau. Eventually, they form neurofibrillary tangles inside nerve cell bodies.When this occurs, the microtubules disintegrate, collapsing the neuron’s transport system.This may result first in malfunctions in biochemical communication between neurons and later in the death of the cells.
The previous drugs like Tacrine(Cognex) – acridine derivative; acts by treating AchE, administrated orally.
The unique quality that a new drug should have for the treatment of alzheimer is thatit should breakup or dissolve the protein tangles that clogs victims brain and result in death of the brain cells and complete loss of memory or death.
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