A new study in mice has made a possible breakthrough in Alzheimer’s research. The team of researchers at the Cleveland Clinic has noted that deleting a single enzyme can reverse the deposition of harmful plaques in the brains of patients with Alzheimer’s disease. This could improve cognitive functions as demonstrated in lab mice. The study appeared this week in the latest issue of the Journal of Experimental Medicine.
The researchers noted that deleting a specific gene that codes for an enzyme called BACE1 can do the trick and reverse cognitive damage caused by Alzheimer’s disease. The enzyme BACE1 works by making the beta-amyloid peptides. These amyloid proteins in turn get accumulated in the brains of these individuals with Alzheimer’s disease. If the accumulation of amyloid proteins could be stopped, the pathological changes associated with Alzheimer’s disease could be reversed say scientists.
Alzheimer’s disease is one of the most debilitating and common age related neurodegenerative disease. There are some typical pathological features of the disease seen in the brain. This includes presence of amyloid protein deposition, progressive loss of nerve synapses, neurofibrillary tangles etc. these lead to severe cognitive function loss. To make these amyloid proteins an enzyme called β-secretase is needed. It is also called β-site amyloid precursor protein (APP)–cleaving enzyme 1 (BACE1). Mutations of the genes K670M671 to N670L671 and A673 to T673 can lead to less amyloid production owing to the stoppage of production of BACE1.
In this study the team used BACE1 inhibitors that could lower the levels of this enzyme. As the levels of the enzyme fell, the neuron loss in the brain also halted. This led to a stoppage in the advancement of the disease that leads to severe memory dysfunction and cognitive loss. If successful in future studies, this could mean a cure for Alzheimer’s for human sufferers. Researchers however add that this may not work on humans in the same manner and may not provide similar results.
Author of the study, Riqiang Yan, explained that the gene that produces the enzyme in the mice was deleted in the mice. This stopped production of the enzyme completely. This complete stoppage may not be possible in humans. However, he said that there are at present five different BACE1 inhibitors that are slated to be tried on humans. They may help cure Alzheimer’s disease and reverse its changes. Authors concluded that “BACE1 inhibition has the full potential to treat AD patients if the drug effectively crosses the blood–brain barrier and retains high potency to inhibit BACE1 activity.”
What remains to be seen is if these agents are well tolerated by humans with few side effects so that they can be used safely over long term. Yan said that the agents are in their phase II and III trials at present.