Toru Kumagai, Ph.D., CEO, medilabo RFP Inc.

"Never forget" New medicines protect your memory

Toru Kumagai, Ph.D., CEO, medilabo RFP Inc.


ML1808 is a combination drug with rifampicin, an amyloid/ tau/ synuclein oligomer inhibitor and resveratrol, a BDNF production inducer. Both show the therapeutic potential for neurodegenerative diseases. ML1808 is being developed as intranasally administered, anti-neurodegenerative disease drug, targeting preclinical to MCI, Alzheimer's disease.
[Rifampicin] Neurodegenerative diseases including Alzheimer's disease are multifactorial disorders with several target proteins contributing to their etiology. Extracellular and intracellular neurotoxic oligomer inhibitor with a broad spectrum such as rifampicin could meet the properties required for the treatment of neurodegenerative diseases.
[Resveratrol] BDNF has a pivotal role in synaptic plasticity and neuronal survival which is related to hippocampal shrinkage and memory decline in elderly and neurodegenerative disease.
Resveratrol showed the diverse biological activities, such as BDNF induction, antioxidant, anti-inflammatory, which can take a therapeutic potential in Alzheimer's disease and other neurodegenerative disease.
[Nasal administration] Nose-to-brain drug transport offers enhancement of drug penetration into the central nervous system and reduction of peripheral exposure. Oral rifampicin improved cognitive impairment in amyloidopathy, tauopathy and synucleinopathy model mice significantly. However, rifampicin shows occasional adverse effects such as liver injury and drug-drug interaction, making it difficult to use for a long period in humans, particularly in elderly people who usually take various medicines. Intranasal administration of rifampicin was found to be effective with lower doses compared to oral administration and safer in terms of hepatotoxicity. Oral resveratrol shows very low bioavailability due to the rapid and extensive metabolism in intestine and liver in human. When intranasally administered in mice, resveratrol showed high bioavailability in the brain.
[Combination therapy] Neurodegenerative disease is complex, with many underlying causes, and tackling more than one will likely be necessary to effectively treat the disease. Nasal administration of rifampicin and resveratrol to amyloidopathy, tauopathy, and α-synucleopathy mice models improved cognitive dysfunction in a dose-dependent and synergistic manner with the two active ingredients. Also, co-administration of rifampicin and resveratrol to mice showed liver tests within normal range. An in vitro reporter gene assay indicates that resveratrol suppresses the inducible expression of CYP3A4 by rifampicin.

As a project leader in Astellas Pharma, 4 drugs were approved for marketing. Then in GE healthcare, promoted a new business "AYUMI EYE" and succeeded in buyout. In 2018, started a new business to develop dementia drugs.