Small molecule oligomer antagonist for Alzheimer’s disease boosts brain connectivity

 Why hasn't our competent? doctors and hospitals looked at this and said: 'Hey, maybe this could help in stroke!' But that won't occur, there aren't two functioning neurons to rub together to get a spark of intelligence in all of stroke!

With your chances of getting dementia post stroke you need solutions. YOUR DOCTOR IS RESPONSIBLE FOR PREVENTING THIS!

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.`    

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018

 

Send me hate mail on this: oc1dean@gmail.com. I'll print your complete statement with your name and my response in my blog. Or are you afraid to engage with my stroke-addled mind? I need an explanation of whom you go to in stroke to ensure valid stroke research get done.

Small molecule oligomer antagonist for Alzheimer’s disease boosts brain connectivity

Results of an ongoing clinical trial showed that an oral, small molecule oligomer antagonist used to treat mild to moderate Alzheimer’s disease boosted connectivity between regions of the brain as a promising sign of cognitive improvement.

Cognition Therapeutics Inc. reported in a press release that data from the SEQUEL study demonstrated treatment with its novel lead therapeutic, CT1812, led to consistent improvement across all prespecified electroencephalography (EEG) parameters, including significant positive change in relative theta power in the central region of the brain and AEC-c, which assesses connectivity between brain regions.

A Pittsburgh-based biotechnology company reported positive results from the SEQUEL study of a novel, oral, once-daily therapeutic to address mild-to-moderate Alzheimer’s disease. Image: Adobe Stock

SEQUEL is a phase 2 randomized, double-blind, single-site study that measured brain wave patterns in 16 adults with mild to moderate AD after 29 days of treatment with either CT1812 or placebo.

According to additional data cited in the release, treatment with once-daily CT1812 — which penetrates the blood-brain barrier and binds selectively to the sigma-2 receptor complex — produced a consistent reduction in global relative theta power and in relative theta power across all regions of the brain. The treatment also resulted in an increased prominence of slower EEG frequencies associated with AD-related cognitive decline.

CT1812 was also well-tolerated, with mild or moderate treatment-emergent adverse events observed in 11 patients in the CT1812-treatment group compared with six in the placebo group, and no adverse events leading to treatment discontinuation, the company said in the release.

Full data were published in The Journal of Prevention of Alzheimer's Disease.

”The gradual slowing of brain wave patterns and impaired connectivity that is a hallmark of Alzheimer’s disease is due to the loss of synapses, which are the connection points between neurons,” Anthony O. Caggiano, MD, PhD, chief medical officer and head of research and development at Cognition Therapeutics, said in the release. “The changes we observed across EEG parameters in SEQUEL may indicate that CT1812 is normalizing brain wave patterns and facilitating communication between different brain regions.”

Sources/Disclosures

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Press Release

Phase II Trial of the Sigma-1 Receptor Agonist Cutamesine (SA4503) for Recovery Enhancement After Acute Ischemic Stroke

I bet this hasn't made any progress toward being used in stroke hospitals. Our fucking failures of stroke associations should already have funded and run a phase III trial of this. But no, press releases are more important. We have NO stroke strategy or stroke leadership in any part of stroke and this will fall thru the cracks. 

Phase II Trial of the Sigma-1 Receptor Agonist Cutamesine (SA4503) for Recovery Enhancement After Acute Ischemic Stroke

1. Roman Urfer, PhD,
2. Hans J. Moebius, MD, PhD,
3. David Skoloudik, MD,
4. Estevo Santamarina, MD,
5. Wakao Sato,
6. Shiro Mita, PhD,
7. Keith W. Muir, MD,
8. for the Cutamesine Stroke Recovery Study Group*

+ Author Affiliations

1. From the M’s Science Corporation, Kobe, Japan (R.U., W.S., S.M.); Moebius-Consult GmbH, Zurich, Switzerland (H.J.M.); Department of Neurology, University Hospital Ostrava, Ostrava, Czech Republic (D.S.); Neurovascular Unit, Hospital Vall Hebron, Barcelona, Spain (E.S.); and Institute of Neuroscience and Psychology, University of Glasgow, Southern General Hospital, Glasgow, Scotland, United Kingdom (K.W.M.).

1. Correspondence to Keith W. Muir, MD, Institute of Neuroscience and Psychology, University of Glasgow, Southern General Hospital, Glasgow G51 4TF, Scotland, United Kingdom. E-mail keith.muir@glasgow.ac.uk

Abstract

Background and Purpose—The σ-1 receptor (Sig-1R) agonist cutamesine (SA4503) enhanced functional recovery after experimental stroke with a treatment initiation window of 48 hours and chronic treatment for 28 days. We conducted a phase 2 clinical trial exploring the safety, tolerability, dose range, and functional effects of cutamesine in patients with ischemic stroke.

Methods—Subjects were randomized between 48 and 72 hours after stroke to receive cutamesine 1 mg/d, 3 mg/d, or placebo for 28 days. Effects on safety and function were assessed at baseline, at end of treatment (day 28), and at end of follow-up (day 56).

Results—In 60 patients, treatment with both cutamesine dosages was safe and well tolerated without significant differences in numbers of treatment emergent or serious adverse events. No significant effect was observed on the primary efficacy measure (change in National Institutes of Health Stroke Scale from baseline to day 56) or modified Rankin Scale and Barthel Index scores. Post hoc analysis of moderately and severely affected patients (baseline National Institutes of Health Stroke Scale, ≥7 and ≥10) showed greater National Institutes of Health Stroke Scale improvements in the 3 mg/d cutamesine group when compared with placebo (P=0.034 and P=0.038, respectively). A trend toward a higher proportion being able to complete a 10m timed walk was observed for cutamesine-treated subjects.

Conclusions—Cutamesine was safe and well tolerated at both dosage levels. Although no significant effects on functional end points were seen in the population as a whole, greater improvement in National Institutes of Health Stroke Scale scores among patients with greater pretreatment deficits seen in post hoc analysis warrants further investigation. Additional studies should focus on the patient population with moderate-to-severe stroke.

Clinical Trial Registration—URL: http://www.clinicaltrials.gov/show/NCT00639249. Unique identifier: NCT00639249. The EudraCT number is 2007-004840-60 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-004840-60/GB).

Effects of the Sigma-1 Receptor Agonist 1-(3,4-Dimethoxyphenethyl)-4-(3-Phenylpropyl)-Piperazine Dihydro-Chloride on Inflammation after Stroke

Get your researcher to propose a stroke therapy protocol based on this research. 

Effects of the Sigma-1 Receptor Agonist 1-(3,4-Dimethoxyphenethyl)-4-(3-Phenylpropyl)-Piperazine Dihydro-Chloride on Inflammation after Stroke

Abstract Top

Activation of the sigma-1 receptor (Sig-1R) improves functional recovery in models of experimental stroke and is known to modulate microglia function. The present study was conducted to investigate if Sig-1R activation after experimental stroke affects mediators of the inflammatory response in the ischemic hemisphere. Male Wistar rats were subjected to transient occlusion of the middle cerebral artery (MCAO) and injected with the specific Sig-1R agonist 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpr​opyl)piperazinedihydrochloride (SA4503) or saline for 5 days starting on day 2 after MCAO. Treatment did not affect the increased levels of the pro-inflammatory cytokines interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin 4 (IL-4), interleukin 5 (IL-5), and interleukin 13 (IL-13) in the infarct core and peri-infarct area after MCAO. In addition, treatment with SA4503 did not affect elevated levels of nitrite, TNF-α and IL-1β observed in primary cultures of microglia exposed to combined Hypoxia/Aglycemia, while the unspecific sigma receptor ligand 1,3-di-o-tolylguanidine (DTG) significantly decreased the production of nitrite and levels of TNF-α. Analysis of the ischemic hemisphere also revealed increased levels of ionized calcium binding adaptor molecule 1 (Iba1) levels in the infarct core of SA4503 treated animals. However, no difference in Iba1 immunoreactivity was detected in the infarct core. Also, levels of the proliferation marker proliferating cell nuclear antigen (PCNA) and OX-42 were not increased in the infarct core in rats treated with SA4503. Together, our results suggest that sigma-1 receptor activation affects Iba1 expression in microglia/macrophages of the ischemic hemisphere after experimental stroke but does not affect post-stroke inflammatory mediators.