20240722_184348

from baseline in MDS-UPDRS part III scores were -4.76 in the high-dose KW-6356 group (95% CI, -6.55 to -2.96), -5.37 in the low-dose KW-6356 group (95% CI, …, 3.48), and -3.14 (95% CI, -4.97 to -1.30) in the placebo group,
Anavex2-73 (blarcamesine), activator of SIGMAR1 (=sigma-1 receptor)	Anavex Life Sciences,	P2, PDD, n=132, a medium (30 mg) or high (50 mg) dose of Anavex 2-73, or to a placebo, for 14 weeks, a MoCA) score of 13 to 23, inclusive, Oral, ANAVEX 2-73-PDD-001 (NCT03774459), Primary: Primary Outcome Measures : Cognitive Drug Research (CDR) Computerized Assessment Continuity of Attention [Results, 20210702] After 14 weeks of treatment, the higher dose, 50 mg, boosted patients' scores on MDS-UPDRS total by nearly 11 points or 18.9% from baseline. Patients taking placebo saw their scores worsen by 3.53 points. An improvement of 7.1 points on that scale is considered clinically meaningful. ANAVEX®2-73 treatment resulted in significant increase in the expression of the SIGMAR1 mRNA biomarker that significantly correlated with improvements in the primary and secondary clinical efficacy endpoints CoA (p = 0.029) and MDS-UPDRS Part III (p = 0.024) and MDS-UPDRS Total (p = 0.038) 14.51-point MDS-UPDRS score improvement compared to placebo (p = 0.034) Previously reported cognitive outcome measures from this study relevant to Alzheimer's disease presented at CTAD 2020 observed statistically significant improvement of CDR system Episodic Memory of +42.22 between ANAVEX®2-73 high dose and placebo, which was dose-dependent (p = 0.003). 7 CDR system Episodic Memory has been shown to be highly correlated (70%) with the ADAS-Cog score (r = 0.7). 8 The calculated corresponding ADAS-Cog mean change from score is -1.9 (improvement) for patients in the high dose group, an 8% mean improvement from baseline to 14 weeks. The difference between the ANAVEX®2-73 group and the placebo group in the change from baseline at 14 weeks was 1.4 point improvement of calculated corresponding ADAS-Cog score (p = 0.015) Biomarker data from ANAVEX®2-73 Ph2 study presented at AD/PD 2022
Pirepemat (IRLAB)	Pirepemat (IRL-752) MOA: 5HT7 and alpha-2 receptor antagonist → leading to increase dopamine and noradrenaline levels. The company highlights pirepemat's potential to treat both frequent falls and dementia in PD	P2b Pirepemat is potential first-in-class treatment for PD Falls; impaired balance and falls are linked to cognitive decline and the progression of PD The ongoing Ph2b study evaluates the dose-response effect in PD patients (55 – 85 yrs) with frequent falls (PD-Fall) Expected enrollment: 165; The primary completion date on CT.gov is not yet updated and rem… Phase 2a results indicated that pirepemat has the potential to improve balance and reduce the risk of falls; the study population was quite small. 32 patients with PD and dementia were enrolled Pirepemat treatment reported 35% improvement in balance and 53% reduction in fall vs. placebo Safe and well tolerated during 4-week treatment with mild adverse events reported during the first 2 weeks of the treatment
SAGE-718 (Sage):		Sage presented Ph2 results on SAGE-718's impact on Mild Cognitive Impairment (MCI) in PD and AD, at AP/PD 2022 and AAN 2022 Positive safety data and signals of cognitive improvement support further evaluation of SAGE-718 in PD and AD RCT trials; However, the AD PD LUMINARY and the PD Ph2 PARADIGM studies are limited based on open-label and small sample size Pha2b RCT trial in PD, PRECEDENT study (NCD05318937), is expected to initiate by mid-2022; AD study to follow thereafter. PARADIGM study (NCT04476017), P2 ol STUDY,
NYX-458 (Aptinyx):		Ph2a data, in patients with cognitive impairment associated, slightly delayed; This is due to COVID-related enrollment slowdown. Data is now expected Q4 2022 / Q1 2023 (previously, planned in 2022) NYX-458 is a novel oral NMDA receptor positive allosteric modulator
ATH-1017 (Athira):	SM specifically designed to enhance the activity of Hepatocyte Growth Factor (HGF) and its receptor, MET	Ph2 SHAPE study in patients with PD Dementia or DLB enrolled patient in Q1 2022 and is expected to complete enrollment in H… ATH-1017 is under development for AD as well. But the trial was cut off at 28 subjects back in October 2022. The small number of patients were randomized to receive either a daily dose of 40 mg or 70 mg of fosgonimeton—or placebo over 26 weeks. The primary endpoint was a combined score of cognitive assessment and working memory, for which fosgonimeton failed to beat placebo.
ALX-001 (Allyx Tx), The molecule was originally identified by Bristol Myers Squibb, but the mechanism of action for neurodegenerative diseases and the identification of ALX-001 as disease-modifying for Alzheimer's disease was discovered by Allyx scientific founder Professor Stephen Strittmatter at Yale.	a silent allosteric modulator of mGluR5, and is a first-in-class compound that selectively blocks the pathogenic activation of the receptor while preserving the normal physiological glutamate signaling that is required for cognition. mGluR5 has been shown to be essential for mediating synaptic dysfunction and loss caused by multiple misfolded extracellular protein species	clinical A 28-day safety study of ALX-001 in Parkinson's disease patients initiated in Q1 2024. announced that its lead compound, ALX-001, is ready to proceed to Ph 2 clinical development in Alzheimer's and Parkinson's disease. The announcement was made in conjunction with the presentation of findings from the company's Phase 1b multiple ascending dose at the AD/PD™ 2024 Conference: The multiple ascending dose (NCT05804383) examined the safety, tolerability and pharmacokinetics of twice-daily oral doses of ALX-001 in 32 healthy adult participants 18-80. Study results show that ALX-001 was safe in cognitively normal adults at all tested doses. ALX-001 achieved high exposure successfully characterized a wide safety window at all doses, which ranged from 50mg to 150mg. Two doses were identified for future studies: 50mg and 100mg. All doses were well-tolerated and there were no serious adverse events. As presented at the International Conference on Alzheimer's and Parkinson's Diseases 2024 (AD/PD™ 2024) this past weekend in Lisbon, Portugal, patients with moderate and severe PD treated with NE3107 appear to have experienced significant improvements in PD symptoms and motor control while placebo-treated patients worsened.1 Furthermore, previous preclinical studies have shown NE3107 is a neuroprotective signal, whereby marmosets treated with NE3107 retained nearly twice as many dopaminergic neurons at the end of study compared to the untreated controls.2 Based on these findings, the Company is planning a Phase 2b for NE3107 as first-line monotherapy for recently diagnosed PD patients needing symptomatic therapy for the first time. The trial targets enrolling 100-150 patients in a 6-month trial with the Part 3 (motor) score on the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) as the primary endpoint. The Bayesian trial design allows an independent data monitoring board to stop the trial as soon as the treatment arm achieves the defined 4-5 points advantage compared to placebo on the UPDRS motor score. The Company anticipates initiating this trial in the late summer of 2024.
BIIB118, Casein kinase 1 inhibitor, small molecule inhibitor of casein kinase 1, or CK1, from Pfizer	CK1 is a key regulator of circadian rhythms that can become dysregulated and contribute to irregular sleep-wake rhythm disorder, or ISWRD, in PD, as well as sundowning in AD	Phase 1
Selegiline (Deprenyl: selegiline, phenylisopropylmethylpropynylamine) & tocoperol	↓ MAO B, tocoperol: ↓ ROS	P3 (DATATOP) (xciii) Early PD 800 (1) active deprenyl, (2) active tocopherol, (3) active deprenyl and tocopherol, or (4) placebo.   xciv) Primary endpoint: time to the development of disability requiring dopaminergic therapy (Ward, 1994 #666) selegine이 이를 9m delay시켰으나, 1m만에 좋아졌으니, rate of progression에는 무영향이고, disease modifying 은 아니고 Symptomatic이다.   xcv) Tocoperol은 무 효과
Inosine: moa: anti-oxidation (urate constitutes the main antioxidant circulating in human plasma.2)	Urate precursor?	P3 ((SURE-PD3) NCT02642393) 298 (n=149 each) Early PD (H&Y 1-2.5) with serum urate <=5.7 (ie PRECEPT에서 quintiles 1-3 군) Cf) normal range: Male: 4-8.5 mg/dL Female: 2.7-7.3 mg/dL 270 Rapid progressor군에 약줘서 slow progressor 로 만들자는 전략. 특히 precept 보니, rapid progressor group is seprated from slow progressor. MDS-UPDRS change (1-3)/24m [results] Active group: serum urate increased 4.6 → 6.63 mg/dL, but no group difference in MDS-UPDRS I-III and DATScan binding 2y Placebo vs one dose to achieve 7.1–8.0 mg (trough) (urate의 정상치는 가변적이지만 대개 남자는 7이하, 여자는 6이하) DSMB determined that SURE-PD3 would be unable to show that inosine slows Parkinson's progression.
	P2 (SURE-PD, NCT00833690) (Parkinson Study Group, 2014 #1295)	)n=75) Early PD with serum urate <=5.8 (Keytruda처럼 Tx response에 따른 patient selection 아니라 아래의 progression에만 근거했네) three treatment arms: placebo or inosine, titrated to produce mild (6.1-7.0 mg/dL) or moderate (7.1-8.0 mg/dL) Primary endpoint: safety RESULTs: i) Serum urate rose by 2.3 and 3.0 mg/dL in the two inosine groups (p<0.001 for each) vs placebo, and CSF urate was greater in both inosine groups (p=0.006 and <0.001, respectively). ii) Secondary analyses demonstrated non-futility of inosine treatment for slowing disability
Not Inosine trials but source data on urate	PRECEPT Schwarzschild, 2008 #663)	Baseline SERUM URATE (mg/dL) UPDRS change (p/year) DATScan change (%/how long?) HR of reaching endpoint <4.3 16.9 -10 1 (reference) 4.3–<5.1 5.1–<5.8 5.8–<6.7 >=6.7 14.3 -4 0.51
	(Ascherio, 2009 #664) 2009 asch	URATE (p/year) (%/how long?) endpoint <3.91 16.37 1 (reference) 3.91–4.60 4.61–5.20 5.21–6.20

Uncertain Spans

location	transcription	uncertainty
KW-6356 fragment at top of page	(95% CI, …, 3.48)	low-dose KW-6356 confidence-interval lower bound is clipped at the top edge of the photo.
Ascherio 2009 table	column captions (p/year) and (%/how long?)	column captions are clipped on the photo and inferred from the analogous PRECEPT table; row order continues beyond the visible body area.