Alzheimer's disease is progressing like an epidemic across the globe. At this stage we need some technology to identify the stage and slow down the progression. The formation of senile plaques and hyperphosphorylated tau protein leads to Aß oligomerization. The aged population suffering from this brain disorder is rising steeply. The statistical data says that in the coming years (i.e. by 2020) 10-14 millions of elderly people would be affected by this disease. We are desperately looking for some techniques to evade and conquer this problem. The researchers have been successful in finding the early diagnostic biomarkers for the problem.
The disorder is 3% genetically inherited. This condition is known as familial AD. The field of genetics can look for some solutions in this area. The researchers are trying to explore the effect of gene therapy on the progression of structural, cognitive and functional decline in mild to moderate to severe AD. Earlier studies have shown that a protein called Nerve Growth Factor (NGF) stimulate the life of acetylcholine neurons that degenerate in neurodegenerative disorder, i.e., Alzheimer's disease (AD). The depletion of Choline can be found in the hippocampal region of the brain resulting in the decrease of membrane synthesis by Phosphomonoester (PME) and increase of membrane breakdown by Phosphodiester (PDE).
The scientists at ARDC are trying to study Nerve Growth Factor to study a gene therapy treatment, CERE-110, which delivers the genes for Nerve Growth Factor directly into the brain. CERE-110 is surgically injected into the Nucleus Basalis of Meynert (NBM), a region in the brain where brain cell death occurs during AD. Researchers hope that the surgical injection of CERE-110 will positively alter the function of Basal Forebrain Cholinergic Neuron (BFCN), keeping these nerves intact despite the degeneration occurring in the brain due to AD. It has already been proved that BFCN is involved in the loss of memory and other cognitive behaviors and in the deterioration of the disorder.
An effective vaccine for Alzheimer's disease has always been a subject of interest for scientists across the globe. The amyloid plaque became the primary target for producing vaccines for AD patients. That first drug, known as AN-1792 which consists of amyloid proteins, was developed to induce the patient's own immune system to attack the amyloid plaques in their brains. The pre clinical trial conducted on animal model (AD transgenic mice) showed remarkable reduction in plaque formation. This prompted the clinicians to move the study further to clinical trial. The data showed 200 elderly subjects with AD tolerated the drug AN-1792 well under the first phase of the trial, but unfortunately, when another 300 subjects were treated in second phase of the clinical trial, around 6% of them developed an allergic inflammation in the brain regions, calling for an immediate termination of the study. After this incident, researchers turned to immunotherapies that depend on passive immunity (to be produced in vitro) against amyloid plaques.
Recently a synthetic antibody, Bapineuzumab is developed to combat the need of current situation. After the failure of active antibody in the clinical trial, the passive immunotherapy came in light. The synthetic vaccine Bapineuzumab is now in progress nationwide. Some big pharmaceutical companies like, Pfizer and Lilly are trying to bring the infusion of synthetic antibodies for AD in the market. It has been indicated that patients with neurodegenerative disorders like, AD, Mild Cognitive Impairment (MCI) pre-AD stage, depression show a potential decrease in the glutathione level in hippocampus, temporal and parietal lobes. These are the regions of the brain that are typically affected in AD. In contrast, a disassociation was observed with increased glutathione level in the AD patients in regions of the frontal lobe that possibly represents compensation for other regions. However, patients with MCI, mood disorder and depression did not show this compensatory action but instead showed a decrease in glutathione level. This suggests that depression may modulate or prevent frontal compensation for other regions like, temporal lobe and hippocampus where the main memory problems arise. The disorders are associated with cognitive behaviors. Meanwhile, some studies indicate improvement in the cognitive abilities following the neuropsychological treatment.
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Geetanjali Murari
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