Estimating the clinical progression of a disease in a standardized way helps communication between medical specialists. For ALS there is the King's college clinical stage progression rate, which is adapted from Braak's staging. Yet it is very difficult in practice to evaluate correctly the stage where an ALS patient stands.

Scientists wanted to estimate King's college clinical stage progression rate (ΔKC) at first clinical evaluation in order to define its predictive and prognostic role on survival in a large cohort of Amyotrophic Lateral Sclerosis (ALS) patients.

They calculated ΔKC with the following formula: 0 - KC clinical stage at first clinical evaluation/disease duration from onset to first evaluation, and each result was reported as absolute value.

All the evaluations were performed in two cohorts: one from their tertiary health centre for motor neuron disease and the other one from a pooled resource open-access ALS clinical trials (PRO-ACT) database.

The tool C-statistic was used to evaluate the model discrimination of survival at different time points (1-3 years). Cox proportional hazard model was used to identify factors associated with survival.

The scientists found that ΔKC predicted survival at three years in their medical centre and in the PRO-ACT cohort. At multivariate analysis, ΔKC was independently associated with survival both in their cohort and in the PRO-ACT cohort.

Based on these results the authors think that ΔKC could be used as a novel measure of disease progression, hence as an accurate predictor of survival in ALS patients. Indeed, greater values of ΔKC were associated with a 3.5-fold higher risk to experience the event, confirming its robust prognostic value.

Read the original article on Pubmed

Contact the author

Advertisement

This book retraces the main achievements of ALS research over the last 30 years, presents the drugs under clinical trial, as well as ongoing research on future treatments likely to be able stop the disease in a few years and to provide a complete cure in a decade or two.

A growing body of evidence suggests that aggregated α-synuclein, the major constituent of Lewy bodies, plays a key role in the pathogenesis of Parkinson's disease and related α-synucleinopathies.

Immunotherapies, both active and passive, against α-synuclein have been developed and are promising novel treatment strategies for such disorders.

Here, scientists report on the humanization and pharmacological characteristics of ABBV-0805, a monoclonal antibody that exhibits a high selectivity for human aggregated α-synuclein and very low affinity for monomers.

ABBV-0805 binds to a broad spectrum of soluble aggregated α-synuclein, including small and large aggregates of different conformations. Binding of ABBV-0805 to pathological α-synuclein was demonstrated in Lewy body-positive post mortem brains of Parkinson's disease patients.

The functional potency of ABBV-0805 was demonstrated in several cellular assays, including inhibition of both neurotoxicity in primary cortical neurons and Fcγ-receptor mediated uptake of soluble aggregated α-synuclein in microglia.

In vivo, the murine version of ABBV-0805 (mAb47) displayed significant dose-dependent decrease of α-synuclein aggregates in brain in several mouse models, both in prophylactic and therapeutic settings.

In addition, mAb47 treatment of α-synuclein transgenic mice resulted in a significantly prolonged survival. ABBV-0805 selectively targets soluble toxic α-synuclein aggregates with a picomolar affinity and demonstrates excellent in vivo efficacy.

Based on the strong preclinical findings described herein, ABBV-0805 has been progressed into clinical development as a potential disease-modifying treatment for Parkinson's disease.

Read the original article on Pubmed

The present study aimed to investigate the effects of dopaminergic medication on voice, speech motor functions, and motor impairment in patients with Parkinson's disease.

Twenty-five individuals with Parkinson disease underwent comprehensive assessment of voice, speech, and motor functions in levodopa medication ON and medication OFF conditions.

Frenchay Dysarthria Assessment and Unified Parkinson's Disease Rating Scale-III were used to evaluate speech motor and motor functions, respectively.

An improvement in lip and laryngeal functioning was found in the medication ON over medication OFF state in both males and females with Parkinson disease.

UPDRS-III scores reduced from the OFF state to the ON state, and no change in dysarthria severity or VHI was found in either gender or medication condition. No correlation was found between speech motor function and motor function or between VHI and acoustic parameters of voice in either medication condition.

Improvement in motor symptoms with levodopa was predominantly observed when compared with the minor improvements in a few aspects of speech motor function and vocal parameters. The results of this study suggest the need for speech therapy as a nonpharmacological treatment method for speech impairments in Parkinson disease.

Read the original article on Pubmed

Parkinson’s disease (PD) is characterized by rigidity, bradykinesia, resting tremor, and postural instability, freezing of gait, hypometria in aiming movements, and micrographia in writing and drawing.

The neural mechanisms and cognitive-motor aspects underlying characteristic deficits in PD remain unclear.

Heterogeneity in Parkinson’s disease presentation has challenged reconciliation of dopaminergic versus nondopaminergic deficits.

Contradictory results are wide spread across studies such as unclear segregation of motor and cognitive task demands.

Dopaminergic mechanisms regulating cognitive and motor control were evaluated comparing visuoperceptual and perceptuomotor functions in Parkinson's disease.

A total of 40 individuals with PD and 42 age and education matched healthy controls (ages range 50–75) consented for participation in this study.

The current study evaluated the role of dopamine in visuoperceptual accuracy versus spatial aspects of movement in idiopathic PD compared to age-matched healthy controls. In order to isolate dopaminergic medication effects on performance, subjects engaged in the experiment twice on and off-medications counterbalanced across visits 1 and 2 (sham on and sham off for controls) with an 8-week interval between visits.

Subjects were examined on computerized tasks of visuoperceptual judgments in vertical and horizontal orientations that were contrasted with spatial accuracy in cursor movement termination relative to targets in different locations. Experimental tasks were designed to segregate spatial accuracy in perception versus aiming movements of variable stimulus lengths (4, 8, and 12 cm lines).

The performance of Parkinson disease patients was contrasted with healthy controls across two separate visits on computerized tasks of perception and aiming to a target at variable stimulus lengths.

Novel visuoperceptual tasks of length equivalence and width interval estimations without motor demands were compared with tasks estimating spatial deviation in movement termination.

The findings support the presence of spatial deficits in early Parkinson disease, more pronounced with increased discrimination difficulty, and with shorter stimulus lengths of 4 cm for both visuoperceptual and perceptumotor functions.

Dopaminergic medication had an adverse impact on visuoperceptual accuracy in particular for length equivalence estimations, in contrast with dopaminergic modulation of perceptuomotor functions that reduced angular displacements toward the target.

The differential outcomes for spatial accuracy in perception versus movement termination in Parkinson disease are consistent with involvement of the direct pathway and models of progressive loss of dopamine through corticostriatal loops.

Future research should develop validated and sensitive standardized tests of perception and explore dopaminergic selective deficits in Parkinson disease to optimize medication titration for motor and cognitive symptoms of the disease.

Read the original article on Pubmed

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative brain disorder. Despite its prevalence and severity, early diagnosis of AD remains a considerable challenge.

Scientists from Duke University, report an integrated acoustofluidics-based diagnostic system (ADx), which combines triple functions of acoustics, microfluidics, and orthogonal biosensors for clinically accurate, sensitive, and rapid detection of AD biomarkers from human plasma.

They also designed and built a surface acoustic wave-based acoustofluidic separation device to isolate and purify Alzheimer's disease biomarkers to increase the signal-to-noise ratio.

Semiconductor metal oxide nanostructures have various compositions and morphologies such as single crystals, one dimensional, and thin or thick film form. Recently, 1D nanoarchitectors have much attraction for sensing due to their aspect ratio beside their thermal and chemical stabilities.

Nanostructures grown by these techniques could adopt the shape of nanowires, nanobelts, nanotubes, nanoneedles, nanorods, etc...

The modifications in surface morphology result in sensing of various kinds of oxidizing and reducing gases like CO, NH3, NO2, H2, O2, H2S, LPG, xylene, propane, toluene, triethylamine, methanol, and acetone.

Multimodal biosensors within the integrated acoustofluidics-based Alzheimer disease diagnostic system were fabricated by in-situ patterning of the ZnO nanorod array and deposition of Ag nanoparticles onto the ZnO nanorods for surface-enhanced Raman scattering (SERS) and electrochemical immunosensors.

This diagnostic system enabled the label-free detections of SERS and electrochemical immunoassay of clinical plasma samples from AD patients and healthy controls with high sensitivity and specificity.

The researchers believe that this efficient integration provides promising solutions for the early diagnosis of AD.

Read the original article on Pubmed

Scientists aimed to investigate the effects and potential mechanisms underlying the action of Shenqi Fuzheng Injection (a Chinese traditional medicine) on a well-established transgenic mouse model of Amyotrophic Lateral Sclerosis.

Shenqi Fuzheng Injection (SFI) is concocted from two kinds of Chinese medicinal herbs, Radix Codonopsis (the root of Codonopsis pilosula; Chinese name: Dangshen) and Radix Astragali (the root of Astragalus; Chinese name: Huangqi).

It is a drug approved by the State Food and Drug Administration of the People’s Republic of China primarily as an antitumor auxiliary injection and marketed in China by Livzon Pharmaceutical Group Inc.

Transgenic SOD1-G93A mice were intraperitoneally injected with SFI three times a week from 87 days of age.

Motor function, survival, pathological manifestations in the brain, and Nrf2 pathway-related assessments of the mice were performed.

SFI marginally reduced motor neuron loss and astrocytic activation in the motor cortex of the brain of SOD1-G93A mice at 130 days of age.

There was a decrease of the level of malondialdehyde and an increase of the levels of superoxide dismutase, Nrf2, heme oxygenase-1, and glutathione S-transferase in the SOD1-G93A mice.

The SFI treatment did not significantly extended the overall survival but improved the pathological manifestations of the brain alleviating the oxydative stress injury and activating the Nrf2 pathway in the animal model of Amyotrophic Lateral Sclerosis.

Read the original article on Pubmed

CRISPR/Cas9-mediated gene activation is a potential therapeutic strategy that does not induce double-strand break (DSB) DNA damage. However, in vivo gene activation via a Cas9 activator remains a challenge, currently limiting its therapeutic applications.

Scientists developed a Cas9 activator nanocomplex that efficiently activates an endogenous gene in the brain in vivo, suggesting its possible application in novel therapeutics. They demonstrated a potential treatment application of the Cas9 activator nanocomplex by activating Adam10 in the mouse brain without introducing insertions and deletions (inDels).

Remarkably, in vivo activation of Adam10 with the Cas9 activator nanocomplex improved cognitive deficits in an Alzheimer's disease (AD) mouse model. These results demonstrate the therapeutic potential of Cas9 activator nanocomplexes for a wide range of neurological diseases.

Read the original article on Pubmed

Cardiac output is dependent on stroke volume and heart rate. A significant portion patients with chronotropic incompetence are unable to increase heart rate to compensate for increased output demand.

Parkinson's disease (PD) as well as Parkinsonism (PS)are of the most common age-related neurodegenerative disorders. Epidemiological studies have shown that Parkinson's disease is accompanied by high rates of premature death compared with the general population.

In general, death in PD/PS is usually caused by determinant factors such as pneumonia, cerebrovascular, and cardiovascular disease. There is a significant body of literature demonstrating involvement of the heart in PD/PS.

In this study, the authors tried to clarify the link between CI and UPDRS part II (off-on), which was calculated by subtracting part II (on) from part II (off), in patients with Parkinson's disease (PD).

Thirty-six hospitalized patients were examined by using cardiopulmonary exercise testing (CPET) for exercise tolerance (ΔVO2/ΔWR and peak VO2/W) and the presence of CI (ΔHR/ΔWR), and using electrocardiogram for heart rate variability.

The patients with Parkinson's disease (PD) who had Chronotropic incompetence, indeed experienced impaired exercise tolerance.

Those patients with Chronotropic incompetence had a difference in the UPDRS part II score when they were on and off. They felt the difference between ‘on’ and ‘off’ in activities of daily living.

The authors conclusions is that in PD patients, the difference between 'on' and 'off' in activities of daily living might be predicted by using ΔHR/ΔWR x100 obtained from CPET as an index.

Read the original article on Pubmed