Stopping dementia at the nose with combination of rifampicin and resveratrol

Dementia is thought to occur when proteins called amyloid-β, tau, and α-synuclein accumulate in the brain and form oligomers. A research group from the Department of Translational Neuroscience, Osaka City University Graduate School of Medicine, had previously shown in a study using mice that the antibiotic rifampicin removes oligomers from the brain and improves cognitive function. However, the drug has been associated with side effects such as liver damage. Resveratrol, a naturally occurring antioxidant in plants, is used as a supplement in Europe and the United States. "To combat the negative side effects of the existing drug rifampicin, we thought of combining it with the hepatoprotective effects of resveratrol," illustrates Professor Takami Tomiyama, who acted as lead investigator for the current study.

This time, the research group administered a fixed dose combination of rifampicin and resveratrol intranasally five days a week for a total of four weeks to mice models of Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies, and observed their cognitive functions and brain pathology. The results showed that the combination significantly improved the cognitive function of the mice, inhibited the accumulation of oligomers, and restored synaptophysin levels - presynaptic proteins that facilitate synapses. Additionally, blood levels of liver enzymes, a marker of hepatic damage that normally increases with rifampicin, remained normal in the fixed-dose combination. Furthermore, increased levels of brain-derived neurotrophic factor (BDNF) expression were observed in the hippocampus, which was not seen with rifampicin alone. These results indicate that this fixed-dose combination is superior to rifampicin alone in terms of both safety and efficacy.

The results of this study were published online in the Swiss scientific journal Frontiers in Neuroscience on December 13, 2021.

"The number of patients with dementia has been increasing all over the world, with some sources predicting a doubling of patients every 20 years. However, there is still no effective treatment for the disease," states Specially Appointed Lecturer Tomohiro Umeda, first author of the study. "Recent studies have shown that abnormalities begin to appear in the brains of dementia patients more than 20 years before the onset of the disease." By investigating new therapeutic purposes with existing drugs in a process called drug repositioning, the research team hopes to diagnose and prevent dementia before the neurons start dying.

Furthermore, based on the team’s previous research experience, nasal administration of a fixed dose combination of rifampicin and resveratrol would increase drug transferability to the brain and further enhance both safety and medicinal effects. The dosage used in this study was 0.02 mg of rifampicin per mouse per day, or 1 mg/kg/day assuming a mouse weight of 20g. "Converted to a human dosage based on body surface area, it becomes 0.081 mg/kg/day," states Prof. Tomiyama, "currently, rifampicin is prescribed at 10 mg/kg/day as an antibiotic, and compared to this, we confirmed an effect at a much lower dosage."

The development of a fixed-dose combination of rifampicin and resveratrol nasal spray is currently being carried out by Medilabo RFP, a venture company originating from the research team’s laboratory. Following the publication of this paper, Medilabo RFP has begun preparations for global clinical trials. In November 2021, with the support of the Japan External Trade Organization (JETRO), Medilabo RFP has established a subsidiary in Massachusetts, USA.

Umeda Tomohiro, Sakai Ayumi, Shigemori Keiko, Yokota Ayumi, Kumagai Toru, Tomiyama Takami.
TITLE=Oligomer-Targeting Prevention of Neurodegenerative Dementia by Intranasal Rifampicin and Resveratrol Combination - A Preclinical Study in Model Mice.
Frontiers in Neuroscience, 2021. doi: 10.3389/fnins.2021.763476

Most Popular Now

COVID-19 can trigger self-attacking antibodies

Infection with the virus that causes COVID-19 can trigger an immune response that lasts well beyond the initial infection and recovery - even among people who had mild sy...

Stopping dementia at the nose with combination of …

Dementia is thought to occur when proteins called amyloid-β, tau, and α-synuclein accumulate in the brain and form oligomers. A research group from the Department of Tran...

Treatments in weeks, not months: Scientists develo…

An international team of scientists has created a plan for an accelerated pipeline for developing drug cocktails to battle the COVID-19 pandemic. The pipeline could speed...

COVID-19 - Omicron: resistant to most monoclonal a…

The Omicron variant was detected for the first time in South Africa in November 2021 and has since spread to many countries. It is expected to become the dominant variant...

Scientists identify antibodies that can neutralize…

An international team of scientists have identified antibodies that neutralize omicron and other SARS-CoV-2 variants. These antibodies target areas of the virus spike pro...

Pfizer and BioNTech sign new global collaboration …

Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) announced a new research, development and commercialization collaboration to develop a potential first mRNA-based v...

Novartis and Molecular Partners report positive to…

Novartis and Molecular Partners announced that Part A of the EMPATHY clinical trial(1) that compared single intravenous doses of ensovibep, a DARPin antiviral therapeutic...

Bayer and Mammoth Biosciences to collaborate on no…

Bayer AG and Mammoth Biosciences, Inc., which is harnessing the diversity of nature to power the next-generation CRISPR products, today announced a strategic collaboratio...

Amgen and Arrakis Therapeutics announce multi-targ…

Amgen (NASDAQ:AMGN) and Arrakis Therapeutics today announced a research collaboration focused on the discovery and development of RNA degrader therapeutics against a rang...

Leiden University Medical Center and Intravacc to …

Intravacc, a global leader in translational research and development of therapeutic vaccines and vaccines against infectious diseases, today announced a partnership with ...

New Vaxzevria data further support its use as thir…

Positive results from a preliminary analysis of an ongoing safety and immunogenicity trial (D7220C00001) showed that Vaxzevria (ChAdOx1-S [Recombinant]), when given as a ...

AstraZeneca and Ionis close agreement to develop a…

AstraZeneca has closed a global development and commercialisation agreement with Ionis Pharmaceuticals, Inc. (Ionis) for eplontersen, formerly known as IONIS-TTR-LRX. ...