Class Of Antibiotics Called Aminoglycosides Can Used To Treat Frontotemporal Dementia
Source: Thailand Medical News Jan 11, 2020 4 years, 11 months, 1 week, 5 days, 6 hours, 22 minutes ago
Medical researchers at the University of Kentucky's College of Medicine have found that a class of
antibiotics called
aminoglycosides could be a promising treatment for
frontotemporal dementia.
University of Kentucky researchers (from left) Matthew Gentry, Haining Zhu and Lisha Kuang
co-authored a study that shows a class of antibiotics could be a promising therapy for
frontotemporal dementia. Credit: Mark Cornelison / UK
Research findings of their proof of concept study, which was a collaborative effort between UK's Department of Molecular and Cellular Biochemistry and the University of California San Francisco's Department of Pathology, were recently published in the journal,
Human Molecular Genetics.
Typically,
frontotemporal dementia is the second-most common
dementia after Alzheimer's disease and 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.
It was found that a subgroup of patients with
frontotemporal dementia have 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.
A research group led by Dr Haining Zhu, a Professor in UK's Department of Molecular and Cellular Biochemistry, discovered that after
aminoglycoside antibiotics were added to neuronal cells with this mutation, the cells started making the full-length
progranulin protein by skipping the mutation.
Dr Matthew Gentry, a co-author of the study and the Antonio S. Turco Endowed Professor in the Department of Molecular and Cellular Biochemistry told
Thailand Medical News, "These patients' brain cells have a mutation that prevents
progranulin from being made. The team found that by adding a small antibiotic molecule to the cells, they could 'trick' the cellular machinery into making it."
The medical 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%.
These study results could be promising to drug development. Currently, there are no effective therapies for any type of
dementia.
Dr Zhu says that after this preclinical proof of concept study, the next step is to study the
antibiotics' effects on mice with the mutation that cause
s
frontotemporal dementia. 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.
Dr Zhu further added to Thailand
Medical News, "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.”
Reference : Lisha Kuang et al, Frontotemporal dementia nonsense mutation of progranulin rescued by aminoglycosides, Human Molecular Genetics (2019). DOI: 10.1093/hmg/ddz280
