Drs. Toru Kumagai and Takami Tomiyama have been on the cutting edge of neurodegenerative research for several years and have recently come one step closer to developing medication that could help improve the quality of life for Alzheimer’s patients as well as those suffering from frontotemporal dementia and dementia with Lewy bodies.
The aggregation of Amyloid-β (Aβ) protein has long been associated with the development of Alzheimer’s Disease (AD) and Dr. Tomiyama has been involved in researching possible treatments since as early as 1994 when his innovative study of the effects of Rifampicin on Aβ was published in the peer-reviewed Biochemical and Biophysical Research Communications journal. In this study Dr. Tomiyama and his team observed that rifampicin, an antibiotic commonly used to treat various bacterial infections from tuberculosis to leprosy, was effective in inhibiting the aggregation of Aβ in vitro. But they also noted that, because of the blood-brain barrier, only 13% of the dosage prescribed in clinical medicine could penetrate into the brain where the toxic Aβ oligomer aggregates and causes the neuron damage that contributes to Alzheimer’s disease and other forms of dementia. Nevertheless, the study indicated that rifampicin or another drug in the rifamycin family showed potential for treating or preventing Alheimer’s disease.
Dr. Tomiyama continued his research and over the course of the subsequent 24 years published four more studies on the effects of rifampicin on amyloid-β and other neurodegenerative proteins and its viability as a cure or treatment. These studies have been published in various peer-reviewed journals such as Oxford’s Brain: A Journal of Neurology, Portland Press’ Biochemical Journal, The American Society for Biochemistry and Molecular Biology’s Journal of Biological Chemistry, and the already mentioned Academic Press’ Biochemical and Biophysical Research Communications journal. But it was the study published in Alzheimer’s Association’s journal Alzheimer’s and Dementia in 2018 that introduced the discussion of intranasal administration of rifampicin. In this study, entitled “Intranasal rifampicin for Alzheimer’s disease prevention”, Dr. Tomiyama and his team were looking for a way to deliver the rifampicin treatment in a way that would not have negative side-effects on the human liver. Using mice with lab modified Aβ, the researchers compared the oral, intranasal, and subcutaneous administration of rifampicin. The results showed that the liver was only significantly affected when using oral administration, in addition, the intranasal and subcutaneous administration improved memory and reduced neuropathologies even more effectively than oral administration. The conclusion was that intranasal administration would be the best option for long-term dosing of rifampicin because of its noninvasive delivery.
In December of 2021 Dr. Tomiyama’s latest study was published in Frontiers in Neuroscience. Even though intranasal rifampicin administration proved to be safer and more effective in reducing the amount of Aβ and other proteins associated with decreased cognitive function, researchers were keen on making its administration as safe as possible – especially since they anticipate treatments to be long term which would increase the risk of negative side-effects on the liver. Their proposed solution was to combine rifampicin with an agent that might neutralize its negative effects; they settled on resveratrol because of its hepatoprotective properties (hepatoprotective means that it has the ability to prevent damage to the liver). Another benefit of resveratrol is that it is a naturally occurring chemical, it is present in red grapes, wine, and juice. Some research indicates that it has high antioxidant potential, and can be helpful for weight loss and treating blood clots, and it is already a widely-used OTC supplement. Dr. Tomiyama’s study showed several advantages to using the rifampicin-resveratrol combination. Not only is it safer for the liver, but resveratrol seems to have its own set of positive effects. Results in the study indicated that resveratrol can aid in the production of nervous tissue.
Because of the success of these studies, Dr. Tomiyama has teamed up with Dr. Toru Kumagai, one of his research partners, to form medilabo RFP, a pharmaceutical company focused on developing treatment to help maintain and improve the quality of life of patients with neurodegenerative disorders. They’ve given their intranasal anti-dementia drug the working name of ML1808, and have entered into phase 2 of its production. They hope to obtain approval for clinical use by 2032. While that still seems very far away, it is encouraging to see that we are closer to understanding and treating neurodegenerative diseases.