Name:	T-817MA
Therapeutic Applications:	Mild to moderate Alzheimer disease
Therapy Types:	Oral, small molecule
Mechanisms:	T-817M is a neurotrophic and neuroprotective compound
Development Status:	investigational in U.S.
FDA Phase:	Phase II/IIa/IIb
Primary Medical Role:	T-817MA inhibits oxidative stress and nitric oxide-induced neurotoxicity and acts as a neurotrophic factor. T-817MA protects against MPTP-induced neurotoxicity by blocking lipid peroxidation in the substantia nigra and striatum (Kawasaki et al., 2008). Neuroprotective effects have been demonstrated in animal models of noise-induced hearing loss and cochlear damage (Yamashita et al., 2008), and in a rat model of schizophrenia, T-817MA is effective in ameliorating sensorimotor gating deficits caused by chronic PCP treatment, possibly via neuroprotective actions (Seo et al., 2008).
Role in Alzheimer's Disease:	T-817MA prevents Aβ-induced granule cell loss in the dentate gyrus of the hippocampus (Nguyen et al., 2007) and increased hippocampal neurogenesis in rats infused ICV with Aβ40 (Kimura et al., 2009). In Aβ-infused rats, T-817MA significantly improved place learning task performance, which may be due to neuroprotective effects in the hippocampus (Nguyen et al., 2007).
Side Effects:	T-817MA has been studied in 100+ healthy people including elderly volunteers who received the drug every day for six weeks. Efficacy and safety profiles will be determined in Phase 2 clinical study NCT00663936 (ClinicalTrials.gov).
Companies:	Toyama Chemical Co. Ltd
Notes:	A Phase 2 clinical trial to test the efficacy and safety of T-817MA in patients with mild to moderate Alzheimer Disease is currently recruiting participants (See NCT00663936 and also Kioku Study The Kioku study is currently enrolling 326 patients at 24 clinics in the US. Patients must have been taking Aricept® (donepezil) for at least 6 months prior to enrollment. Patients who are taking any drug other than donepezil for Alzheimer's disease, including rivastigmine (Exelon®), galantamine (Razadyne®), or tacrine (Cognex®) will be excluded from this study. Patients who are taking memantine (Namenda™) within eight (8) weeks of the Baseline Visit (Visit 2) will also be excluded from this study. Patients with medical conditions such as insulin-dependent diabetes or severe heart disease are excluded from this trial. This entry was posted on April 23, 2009.

References

Fukushima T, Koide M, Ago Y, Baba A, Matsuda T. T-817MA, a novel neurotrophic agent, improves sodium nitroprusside-induced mitochondrial dysfunction in cortical neurons. Neurochem Int. 2006 Jan;48(2):124-30. Abstract

Hirata K, Yamaguchi H, Takamura Y, Takagi A, Fukushima T, Iwakami N, Saitoh A, Nakagawa M, Yamada T. A novel neurotrophic agent, T-817MA [1-{3-[2-(1-benzothiophen-5-yl) ethoxy] propyl}-3-azetidinol maleate], attenuates amyloid-beta-induced neurotoxicity and promotes neurite outgrowth in rat cultured central nervous system neurons. J Pharmacol Exp Ther. 2005 Jul;314(1):252-9. Abstract

Kawasaki T, Ago Y, Kitao T, Nashida T, Takagi A, Takuma K, Matsuda T. A neuroprotective agent, T-817MA (1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} azetidin-3-ol maleate), prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice. Neuropharmacology. 2008 Oct;55(5):654-60. Abstract

Nguyen PT, Kimura T, Ho SA, Tran AH, Ono T, Nishijo H. Ameliorative effects of a neuroprotective agent, T-817MA, on place learning deficits induced by continuous infusion of amyloid-beta peptide (1-40) in rats. Hippocampus. 2007;17(6):443-55. Abstract

Seo T, Sumiyoshi T, Tsunoda M, Tanaka K, Uehara T, Matsuoka T, Itoh H, Kurachi M. T-817MA, a novel neurotrophic compound, ameliorates phencyclidine-induced disruption of sensorimotor gating. Psychopharmacology (Berl). 2008 Apr;197(3):457-64. Abstract

Yamashita D, Shiotani A, Kanzaki S, Nakagawa M, Ogawa K. Neuroprotective effects of T-817MA against noise-induced hearing loss. Neurosci Res. 2008 May;61(1):38-42. Abstract

Kimura T, Hong Nguyen PT, Ho SA, Tran AH, Ono T, Nishijo H. T-817MA, a neurotrophic agent, ameliorates the deficits in adult neurogenesis and spatial memory in rats infused i.c.v. with amyloid-beta peptide. Br J Pharmacol. 2009 Apr 3. Abstract