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Restoration of brain function via artificial neural connection - Restoration of locomotor function via artificial neural connection in individuals with spinal cord injury

开始日期2017-04-01

申办/合作机构

Tokyo Metropolitan Institute of Medical Science

JPRN-UMIN000021966

/ CompletedN/A

Project for Promotion of Community Care Program for People Living With Dementia - Development of Japanese version of BPSD Program of Care

开始日期2016-09-01

申办/合作机构

Tokyo Metropolitan Institute of Medical Science

JPRN-UMIN000023742

/ Unknown statusN/AIIT

Study of factors of virus and host sassociated with severe Enterovirus diseases - Study of severe Enterovirus diseases

开始日期2016-07-01

申办/合作机构

Tokyo Metropolitan Institute of Medical Science

100 项与 Tokyo Metropolitan Institute of Medical Science 相关的临床结果

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0 项与 Tokyo Metropolitan Institute of Medical Science 相关的专利（医药）

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3,084

项与 Tokyo Metropolitan Institute of Medical Science 相关的文献（医药）

2025-07-01·Sleep Medicine

Clinical challenges in narcolepsy: From delayed diagnosis to daytime function impairments during treatment

Article

作者: Kokubo, Kinya ; Honda, Makoto ; Inoue, Yuichi ; Kumagai, Takuya ; Shoji, Ayako

OBJECTIVEWhile a delayed diagnosis of narcolepsy is common, the reasons are not well understood. Additionally, only few systematic studies have focused on the daytime function of treated patients. In this cross-sectional online survey, we aimed to investigate the predictive factors for diagnostic delays and daytime dysfunction in Japanese patients with narcolepsy undergoing treatment.METHODThis survey included individuals aged 16 years or older with a confirmed diagnosis of narcolepsy. The participants completed a questionnaire related to disease diagnosis and current daytime function, including quality of life measured with Short Form-8 (SF-8) and work performance measured with the Work Productivity and Activity Impairment (WPAI) questionnaire.RESULTSThe study enrolled 248 of the 250 respondents. The mean time from symptom onset to definitive diagnosis was 8.7 years. Diagnostic delay was significantly associated with the year of symptom onset (<2005 vs. ≥2005), age at symptom onset (<16 vs. ≥16 years), narcolepsy type (without or with cataplexy), residence (rural vs. urban), and information sources about the disorder. The participants had a lower mental component summary score in SF-8 and higher WPAI absenteeism, presenteeism, and overall work impairment scores than the general Japanese population. Severe daytime sleepiness (Epworth Sleepiness Scale score ≥16) and younger age were associated with a poor mental component summary score and higher presenteeism and overall work impairment.CONCLUSIONSImproving sleepiness is crucial to optimize the patients' daytime functioning. A treatment system that addresses regional disparities in narcolepsy care is needed, along with increased public awareness, especially in educational settings.

2025-06-01·Molecular Therapy Nucleic Acids

Correcting tau isoform ratios with a long-acting antisense oligonucleotide alleviates 4R-tauopathy phenotypes

Article

作者: Watanabe, Hirohisa ; Sahashi, Kentaro ; Watanabe, Eri ; Mohammad, Moniruzzaman ; Ishigaki, Shinsuke ; Kanamitsu, Kayoko ; Okada, Yohei ; Hirai, Shinobu ; Ishibashi, Minaka ; Iwade, Nobuyuki ; Neya, Masahiro ; Katsuno, Masahisa ; Okado, Haruo ; Tuerde, Dilina ; Sobue, Gen ; Aldoghachi, Asraa Faris ; Fujiwara, Tsuyoshi ; Fujioka, Yusuke ; Kawai, Kaori ; Iwata-Endo, Kuniyuki

Tau, a microtubule-binding protein linked to tauopathies like Alzheimer's disease and frontotemporal lobar degeneration (FTLD), has 3-repeat (3R) and 4-repeat (4R) isoforms. Accumulation of the 4R-tau is associated with FTLD, progressive supranuclear palsy (PSP), and cortico-basal degeneration (CBD). We previously showed that a loss of fused in sarcoma (FUS) or splicing factor, proline- and glutamine-rich (SFPQ) promoted 4R-tau accumulation, which induced FTLD-like behaviors and neurodegeneration in mice. Here, we developed antisense oligonucleotides (ASOs) modified with 2'-O, 4'-C-ethylene-bridged nucleic acids (ENAs), reducing the 4R-tau/3R-tau ratio while maintaining total tau expression from the MAPT gene. In vitro screening identified EN-06 as the most effective ENA. Intracerebroventricular (ICV) administration of EN-06 corrected the 4R/3R-tau ratio in FUS-silenced humanized tau mice and human iPSC-derived neurons. This treatment ameliorated disease phenotypes, including aberrant behaviors, spine dysmorphology, and neurodegeneration. The half-life of EN-06 after a single ICV administration was approximately 6 months in the brain, with splicing correction effects that persisted for 2 years. The efficacy of EN-06 was higher than that of 2'-O-methoxyethyl (MOE)-modified ASO (MO-06). These findings highlight the potential of ENA-modified ASOs to reduce 4R-tau while preserving total MAPT expression, thus offering a safe and long-acting treatment for 4R-tau-associated tauopathies.

2025-05-01·BJPsych Open

Association between plasma glucuronic acid levels and clinical features in schizophrenia

Article

作者: Yamasaki, Syudo ; Nishida, Atsushi ; Miyashita, Mitsuhiro ; Tabata, Koichi ; Usami, Satoshi ; Suzuki, Kazuhiro ; Arai, Makoto ; Kamiguchi, Hidenori ; Toriumi, Kazuya ; Yamaguchi, Satoshi ; Itokawa, Masanari

BackgroundGlucuronic acid (GlcA) is crucial in the glucuronidation pathway, facilitating the metabolism and elimination of various substances and drugs. Recent studies have noted elevated GlcA levels in patients with schizophrenia (SCZ) compared with healthy individuals. However, it remains unclear whether this elevation contributes to SCZ pathophysiology or results from medication effects.AimsThis study investigated the relationship between peripheral GlcA levels and clinical characteristics in patients with SCZ and assess whether these associations persist independently of psychotropic medication effects to provide insight into the potential role of GlcA in the pathophysiology of SCZ.MethodsPlasma GlcA levels were analysed in 218 patients with SCZ, examining their association with clinical features. The correlation between GlcA levels and symptom severity, assessed using the Positive and Negative Syndrome Scale (PANSS), was analysed in 35 patients. In addition, multiple regression analysis was conducted to adjust for age and psychotropic medication effects.ResultsSignificant correlations were observed between GlcA levels and PANSS scores for negative symptoms, general psychopathology and total scores. After adjustment for age and psychotropic medications, significant correlations between GlcA levels and PANSS scores persisted for negative symptoms (adjusted β [95% CI], 13.926 [2.369, 25.483]) and general psychopathology (adjusted β [95% CI], 19.437 [3.884, 34.990]), while the total score was no longer significant (adjusted β [95% CI], 34.054 [–0.517, 68.626]).ConclusionsElevated GlcA levels in patients with SCZ are associated with specific symptom severity irrespective of the medication dose, suggesting a potential role of GlcA in SCZ pathophysiology.

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