Researchers investigating a new Alzheimer’s treatment gives hope for the sixth leading cause of death in the United States.
A new way to combat deadly dementia.
Did you know Alzheimer’s Disease is the sixth leading cause of death in the United States? Alzheimer’s disease is just one type of a group of conditions known as dementia that involves memory loss and that tends to affect the elderly. Alzheimer’s disease is the most common type of dementia. There are no drugs are on the market that can completely cure Alzheimer’s disease. The few drugs that we have for Alzheimer’s disease can help with the symptoms but won’t cure the patient. Currently, drugs for Alzheimer’s target one of two chemicals in the human brain related to memory, acetylcholine or glutamate. Researchers have found a promising new Alzheimer’s treatment to help with the symptoms of Alzheimer’s that may even be able to reverse the deadly disease.
In an article from Scientific Reports, researchers took a molecule called AC253 that can block the action of amylin – a key molecule implicated in Alzheimer’s disease – and then broke it down into smaller fragments. In mouse studies, AC253 has shown potential for blocking the action of amylin and thus potentially preventing Alzheimer’s. However, AC253 is a large molecule and has trouble getting into the brain where it needs to work. Smaller fragments of AC253 have an easier time getting into the brain where Alzheimer’s disease does its damage to the human body. Since the brain is where a drug would need to be to fight Alzheimer’s, these smaller fragments have an advantage over the original molecule they were taken from. When looking for potential fragments to test, researchers predicted the ones that could be effective in the human body by looking at each fragment’s molecular structure and chemistry. The fragments of AC253 most likely to be effective were tested on cells and found to protect human brain cells from amylin-related protein buildup, which is closely linked with Alzheimer’s disease. Brain tissue was obtained from mice and was used to further test the fragments. The results showed that just one of the fragments, called ‘R5,’ stood out in its ability to move into the brain where it needs to be to fight Alzheimer’s disease. In other words, the R5 fragment worked much better than all the other fragments and the original AC253 molecule. Mice that were bred to have Alzheimer’s disease were treated with the R5 fragment of AC253 and examined for improvement in protein buildup. In mice brains, it was found that the R5 fragment could still block the protein buildup caused by amylin the way that AC253 does, despite being just a portion of the original molecule. Researchers were able to determine that in mice, this new, smaller molecule can block the buildup of protein thought to be linked with Alzheimer’s. Not only did this potential new drug look promising under the microscope, but it also helped with the symptoms in mice. Alzheimer’s patients often forget where they are and tend to get lost. The mice given the AC253 fragment also showed improvement in their sense of direction in addition to having less protein buildup on their brain cells.
While this is just one study done in mice, it gives us a clue of where to look for a new Alzheimer’s treatment. It might be quite some time before this R5 fragment is made into a drug that is used to treat Alzheimer’s, but these are important first steps. The next steps will be further research into this smaller molecule and once it seems safe, research can begin in humans.
Written by Ramsey Akel
References:
Facts and Figures. Alzheimer’s Disease and Dementia. https://www.alz.org/alzheimers-dementia/facts-figures. Accessed September 20, 2019.
Soudy R, Patel A, Fu W, et al. Cyclic AC253, a novel amylin receptor antagonist, improves cognitive deficits in a mouse model of Alzheimers disease. Alzheimers & Dementia: Translational Research & Clinical Interventions. 2017;3(1):44-56. doi:10.1016/j.trci.2016.11.005.
Soudy R, Kimura R, Patel A, et al. Short amylin receptor antagonist peptides improve memory deficits in Alzheimer’s disease mouse model. Scientific Reports. 2019;9(1). doi:10.1038/s41598-019-47255-9.
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