Bypassing the liver
Japanese scientists have completed preclinical trials of a spray for dementia
Sergey Vasiliev, Naked Science
Japanese scientists have announced the completion of preclinical trials of an intranasal drug that slows down the development of neurodegenerative processes. The drug uses a pair of widely used drugs and has worked successfully in experiments on mice without causing dangerous side effects. This is stated in an article published in the journal Frontiers in Neuroscience (Umeda et al., Oligomer-Targeting Prevention of Neurodegenerative Dementia by Intranasal Rifampicin and Resveratrol Combination – A Preclinical Study in Model Mice). Briefly about the work is described in the press release Osaka City University.
Alzheimer's disease and some other neurodegenerative diseases are closely related to the accumulation of dense clumps of amyloid proteins in neurons, which eventually cause their death and destruction of the entire structure of the brain. A few years ago, Takami Tomiyama and his colleagues showed that taking the well-known semisynthetic antibiotic rifampicin slows down the accumulation of amyloids if used at the earliest stages of the disease.
Doctors use rifampicin in the treatment of tuberculosis, but with caution, because it has a toxic effect on the liver. Therefore, despite the encouraging results obtained in laboratory mice, Japanese scientists were in no hurry to proceed to human trials, but instead began to look for ways to protect the liver from rifampicin. To do this, they decided to inject the drug intranasally, which allows the substance to enter the brain faster, bypassing the passage through the liver.
In addition, a drug capable of reducing its hepatotoxic effect was selected as a pair of antibiotics. A suitable substance turned out to be resveratrol — a well-known antioxidant, which is found, in particular, in the peel of grapes (and wine). In new experiments, Tomiyama and his co-authors tested the effect of the combined drug rifampicin and resveratrol when administered intranasally to mice.
The experiments used animals of various model lines obtained to study neurodegenerative processes in the brain. They received rifampicin and resveratrol five times a week for a month, and subsequently demonstrated the absence of amyloid plaques and improved cognitive abilities compared to the control group mice. At the same time, no signs of liver damage were noticed in them.
The authors note that the amount of antibiotics needed to protect against Alzheimer's disease is orders of magnitude less than those used in the treatment of tuberculosis — less than 0.1 milligrams per kilogram of body weight versus 10 milligrams per kilogram. All this sounds very encouraging and allows us to prepare for clinical trials of the combined drug in humans. Japanese scientists plan to do this in the near future.
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