Open-Label Placebo Administration Decreases Pain in Elderly Patients With Symptomatic Knee Osteoarthritis - A Randomized Controlled Trial.

Background: Recent studies indicate that the administration of open-label placebos (OLP) can improve symptoms in various medical conditions. The primary aim of this 3-week randomized controlled trial was to examine the effects of OLP treatments on pain, functional disability, and mobility in patients with arthritic knee pain. Methods: Sixty patients (55% females; mean age, 66.9 ± 9.7 SD years) were randomized to one of two OLP treatments (n = 41) or no treatment (NT; n = 19). OLP treatments were accompanied by the verbal suggestion "to decrease pain" (OLP-pain, n = 20) or "to improve mood" (OLP-mood, n = 21). Pain and mood levels were monitored on 11-point Numeric Rating Scales (NRSs) in a patient diary, and global clinical improvement (CGI-I) was assessed at the end of the study. At baseline and after 21 days, patients filled in validated questionnaires to assess symptoms and functional disability of the knee (WOMAC), mental and physical quality of life (SF-36), state anxiety (STAI-state), perceived stress (PSQ-20), and self-efficacy (GSE). In addition, knee mobility (neutral zero-method), heart rate variability (HRV), and diurnal cortisol levels were evaluated before and after treatment. Results: Evaluation of daily pain ratings indicated significant pain decrease in the OLP groups compared to NT (p = 0.013, d = 0.64), with no difference between the OLP-pain and the OLP-mood groups (p = 0.856, d = 0.05). OLP treatment also improved WOMAC pain (p = 0.036, d = 0.55), again with no difference between the two OLP groups (p = 0.65, d = 0.17). WOMAC function and stiffness, knee mobility, stress, state anxiety, quality of life, and self-efficacy did not change differently between groups. Conclusion: OLP treatment improved knee pain in elderly patients with symptomatic knee osteoarthritis (OA), while functional disability and mobility of the knee did not change. The content of the verbal suggestion was of minor importance. OLP administration may be considered as supportive analgesic treatment in elderly patients with symptomatic knee OA. Trial Registration: German Clinical Trials Register (https://www.drks.de/), DRKS00015191 (retrospectively registered).

QIAD assay for quantitating a compound's efficacy in elimination of toxic Aß oligomers.

Strong evidence exists for a central role of amyloid ß-protein (Aß) oligomers in the pathogenesis of Alzheimer's disease. We have developed a fast, reliable and robust in vitro assay, termed QIAD, to quantify the effect of any compound on the Aß aggregate size distribution. Applying QIAD, we studied the effect of homotaurine, scyllo-inositol, EGCG, the benzofuran derivative KMS88009, ZAß3W, the D-enantiomeric peptide D3 and its tandem version D3D3 on Aß aggregation. The predictive power of the assay for in vivo efficacy is demonstrated by comparing the oligomer elimination efficiency of D3 and D3D3 with their treatment effects in animal models of Alzheimer´s disease.

A synthetic amino acid substitution of Tyr10 in Aß peptide sequence yields a dominant negative variant in amyloidogenesis.

Alzheimer's disease (AD) is the most common cause of dementia in elderly people, and age is the major nongenetic risk factor for sporadic AD. A hallmark of AD is the accumulation of amyloid in the brain, which is composed mainly of the amyloid beta-peptide (Aß) in the form of oligomers and fibrils. However, how aging induces Aß aggregation is not yet fully determined. Some residues in the Aß sequence seem to promote Aß-induced toxicity in association with age-dependent risk factors for AD, such as (i) increased GM1 brain membrane content, (ii) altered lipid domain in brain membrane, (iii) oxidative stress. However, the role of Aß sequence in promoting aggregation following interaction with the plasma membrane is not yet demonstrated. As Tyr10 is implicated in the induction of oxidative stress and stabilization of Aß aggregation, we substituted Tyr 10 with a synthetic amino acid that abolishes Aß-induced oxidative stress and shows an accelerated interaction with GM1. This variant peptide shows impaired aggregation properties and increased affinity for GM1. It has a dominant negative effect on amyloidogenesis in vitro, in cellulo, and in isolated synaptosomes. The present study shed new light in the understanding of Aß-membrane interactions in Aß-induced neurotoxicity. It demonstrates the relevance of Aß sequence in (i) Aß-membrane interaction, underlining the role of age-dependent enhanced GM1 content in promoting Aß aggregation, (ii) Aß aggregation, and (iii) Aß-induced oxidative stress. Our results open the way for the design of peptides aimed to inhibit Aß aggregation and neurotoxicity.

In vitro and in vivo staining characteristics of small, fluorescent, Abeta42-binding D-enantiomeric peptides in transgenic AD mouse models.

One of the characteristic pathological hallmarks of Alzheimer's disease (AD) are neuritic plaques that consist of amyloid peptide (Abeta). To improve diagnosis and treatment evaluation, neuroimaging tools that make use of Abeta-binding ligands to visualise amyloid plaques are being developed. We investigate the in vitro and in vivo characteristics of a series of three D-enantiomeric peptides (D1-D3) that were developed to specifically bind amyloid beta1-42 (Abeta42) in the brains of transgenic AD-model mice. We stained brain sections of the mice, injected and infused the mice with these small D-peptides, and examined their staining of Abeta42 in the brain. The experiments demonstrate that the D-peptides label all plaques that contain Abeta42 in the brain. In contrast, diffuse amyloid beta deposits (which do not contain Abeta42) are not stained by any of the D-peptides. The in vivo and in vitro studies demonstrate that the D-peptides label all Abeta42 in the brain, and none of the D-peptides causes inflammation or is taken up by astrocytes or microglia. Furthermore, long-term infusion of the peptides does not cause inflammation. Together, this demonstrates that these D-peptides might be suitable for use as molecular probes to measure Abeta plaque load in the living brain for early diagnosis of Alzheimer's disease, or to monitor Abeta42 plaque load during disease progression or during treatment.