Tamibarotene (
Am80), a synthetic
retinoid approved in Japan for treatment of
acute promyelocytic leukemia (APL), is a
retinoic acid receptor (RAR) agonist with high specificity for RARα and RARβ over RARγ. Temporarily and spatially specific expression of RARs suggests their pivotal roles in the adult brain.
Am80 is considered to be a promising candidate
drug for treatment of
Alzheimer's disease (AD) because of its transcriptional controls of multiple target genes involved in etiology and pathology of AD. In APP23 AD model mice, administration of
Am80 decreased the deposition of insoluble amyloid-β(42). In senescence-accelerated mice (SAMP8),
Am80 ameliorated the decrease of cortical
acetylcholine, as well as reducing anxiety in behavioral tests and improving the sleep deficit.
Am80 also effected a significant improvement of memory in the rat
scopolamine-induced
memory deficit model. Like other
retinoids,
Am80 also has an immunomodulatory effect and reduces secretion of proinflammatory
cytokines and
chemokines by astrocytes and microglia surrounding
amyloid-β plaques. In a rat
experimental autoimmune encephalomyelitis model,
Am80 reduced inflammatory
cytokines and showed significant efficacy.
Retinoids also promote differentiation of neural stem cells, and
Am80 improved the recovery of spinal cord-injured rats.
Am80 may also improve vascular factors involved in onset and/or progression of AD.
Am80 has been in clinical use for treatment of APL in Japan since 2005, and has been reported to have fewer side effects than other
retinoids. We have recently started a clinical study to evaluate the efficacy and safety of
Am80 for the treatment of
Alzheimer's disease.