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Potential treatment to prevent dementia

Neurodegenerative dementia is an umbrella term for neurodegenerative diseases that have the main clinical symptom of dementia.

Alzheimer’s disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB) are three such neurodegenerative dementia diseases.

While people with Parkinson’s disease can develop dementia—it only happens when the protein aggregations spread into the cerebral cortex of the brain.

All three diseases can be characterized by the accumulation of certain polymers of proteins within different cells of the brain: amyloid-β [or Aβ] and tau within AD, tau in FTD, and α-synuclein in DLB.

To date there is no cure or even reliable treatment for any of these diseases, despite the research efforts of scientists and pharmaceutical companies. 

In part, many of the drugs developed to treat these diseases have failed to improve patients’ cognitive functions in clinical trials.

These clinical trial ‘failures’ can be attributed to two reasons: “the late timing of medication and the wrong drug target”. 1

While the disease cannot be cured yet, it is suggested that treatment starts earlier—prior to the progression of neurodegeneration, and that medicines target the oligomers (the ‘building blocks’ of the insoluble polymers).

In a preclinical study with mice models for AD, FTD, and DLB, scientists at Osaka City University Graduate School of Medicine have shown that the combination of an antibiotic (rifampicin) and an antioxidant (resveratrol) given intranasal reduced the amount of toxic oligomers in the brains of mice.

Using well-studied mice models of the different diseases, the scientists were able to determine the ‘pre-neurodegeneration’ point for each model—and started the trial one-month prior to the onset of neurodegeneration.

After the trial, there were reductions in the amount of toxic oligomers in the brains of mice given the treatment compared to controls, and improvement in cognition (again compared to controls). 

While this is a promising step in treatment of neurodegenerative dementia, the authors do state that it will be a while before the drug combination can make it to human trials (with more tests still needed). 

While it could still be possibly years before this drug combination (or others) makes it into human clinical trials—this preclinical study has laid the building blocks for taking a different look at how to treat (and even possibly prevent) neurodegenerative dementia.

Reference:

Umeda T, Sakai A, Shigemori K, Yokota A, Kumagai T, and Tomiyama T. (2021) “Oligomer-Targeting Prevention of Neurodegenerative Dementia by Intranasal Rifampicin and Resveratrol Combination—A Preclinical Study in Model Mice” Frontiers in Neuroscience 15:763476 doi: 10.3389/fnins.2021.763476

Image by Gerd Altmann from Pixabay 

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