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    • Antibiotics could be...

    Antibiotics could be promising therapy for certain forms of dementia

    Written by Medha Baranwal Baranwal Published On 2020-01-11T20:10:18+05:30  |  Updated On 11 Jan 2020 8:10 PM IST
    Antibiotics could be promising therapy for certain forms of dementia

    USA: Frontotemporal dementia is the most common type of early-onset dementia. It typically begins between ages 40 and 65 and affects the frontal and temporal lobes of the brain, which leads to behavior changes, difficulty speaking and writing, and memory deterioration. Now, a recent study published in the journal Human Molecular Genetics has found a class of antibiotics called aminoglycosides to be a promising treatment for frontotemporal dementia.


    These results could be promising for drug development. Currently, there are no effective therapies for any type of dementia.


    A subgroup of patients with frontotemporal dementia has a specific genetic mutation that prevents brain cells from making a protein called progranulin. Although progranulin is not widely understood, its absence is linked to the disease.


    "These patients' brain cells have a mutation that prevents progranulin from being made. The researchers found that by adding a small antibiotic molecule to the cells, they could 'trick' the cellular machinery into making it," said Matthew Gentry, a co-author of the study and the Antonio S. Turco Endowed Professor in the Department of Molecular and Cellular Biochemistry.


    Haining Zhu, Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, and colleagues discovered that after the addition of aminoglycoside antibiotics to neuronal cells with this mutation, the cells started making the full-length progranulin protein by skipping the mutation.


    The researchers found two specific aminoglycoside antibiotics - Gentamicin and G418 - were both effective in fixing the mutation and making the functional progranulin protein. After adding Gentamicin or G418 molecules to the affected cells, the progranulin protein level was recovered up to about 50 to 60%.


    After this preclinical proof of concept study, the next step is to study the antibiotics' effects on mice with the mutation that causes frontotemporal dementia, Zhu says. Another focus is to possibly develop new compounds from Gentamicin and G418 that could be safer and more effective. Although Gentamicin is an FDA-approved medication, its clinical usage is limited as it is associated with a number of adverse side effects.


    "If we can get the right resources and physician to work with, we could potentially repurpose this drug. This is an early stage of the study, but it provides an important proof of concept that these aminoglycoside antibiotics or their derivatives can be a therapeutic avenue for frontotemporal dementia," said Zhu.


    The study, "Frontotemporal dementia nonsense mutation of progranulin rescued by aminoglycosides," is published in the journal Human Molecular Genetics.


    DOI: https://doi.org/10.1093/hmg/ddz280

    aminoglycosidesantibioticsdementiafrontotemporal dementiaHaining ZhuHuman Molecular Geneticsprogranulin
    Source : With inputs from Human Molecular Genetics

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    Medha Baranwal Baranwal
    Medha Baranwal Baranwal
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