Neurodegenerative disease management最新文献

The actual standard treatment for mild-to-moderately severe Alzheimer's disease only attacks its symptoms. Masitinib is a potent and selective phenylaminothiazole-type tyrosine kinase inhibitor which is currently in Phase III studies for the treatment of Alzheimer's disease (AD) with the aim of modifying its evolution and with multiple pharmacological targets such as inhibition of mast cells activity, inhibition of microglia activation, modulation of Aβ and Tau protein signaling pathway and prevention of synaptic damage. Here, we review the preclinical and clinical studies that investigated the administration of masitinib treatment in monotherapy in AD. All research studies revealed positive effects concerning the cognitive functions in AD and generally with good safety and tolerability.

Aim: To investigate the patients' perception of their disease, its management and the impact of the COVID-19 pandemic on persons living with amyotrophic lateral sclerosis (ALS) in Malaysia. Patients & methods: An online survey comprising 42 questions was conducted on ALS patients during the peak of the COVID-19 pandemic. Results: Responses were received from 37/60 (62%) participants with ALS directly or through their caregivers. During the COVID-19 pandemic, two-thirds of patients were negatively impacted by the sudden disruption to their hospital appointments, rehabilitation sessions and reduced social interactions. Conclusion: This study provided insight into patients' perception of their care and management of ALS in Malaysia which will facilitate in implementing changes that can improve care to persons living with this devastating illness.

Intraoperative neurophysiological information could increase accuracy of surgical deep brain stimulation (DBS) lead placement. Subsequently, DBS therapy could be optimized by specifically targeting pathological activity. In Parkinson's disease, local field potentials (LFPs) excessively synchronized in the beta band (13-35 Hz) correlate with akinetic-rigid symptoms and their response to DBS therapy, particularly low beta band suppression (13-20 Hz) and high frequency gamma facilitation (35-250 Hz). In dystonia, LFPs abnormally synchronize in the theta/alpha (4-13 Hz), beta and gamma (60-90 Hz) bands. Phasic dystonic symptoms and their response to DBS correlate with changes in theta/alpha synchronization. In essential tremor, LFPs excessively synchronize in the theta/alpha and beta bands. Adaptive DBS systems will individualize pathological characteristics of neurophysiological signals to automatically deliver therapeutic DBS pulses of specific spatial and temporal parameters.

The continuous neuroinflammatory and neurodegenerative pathology in multiple sclerosis (MS) results in irreversible accumulation of physical and cognitive disability. Reliable early detection of MS disease processes can aid in the diagnosis, monitoring and treatment management of MS patients. Recent assay technological advancements now allow reliable quantification of serum-based neurofilament light chain (sNfL) levels, which provide temporal information regarding the degree of neuroaxonal damage. The relationship and predictive value of sNfL with clinical and cognitive outcomes, other paraclinical measures and treatment response is reviewed. sNfL measurement is an emerging, noninvasive and disease-responsive MS biomarker that is currently utilized in research and clinical trial settings. Understanding sNfL confounders and further assay standardization will allow clinical implementation of this biomarker.

New therapies for symptoms in Alzheimer's disease (AD) are urgently needed. Prior studies suggest that transcranial direct current stimulation (tDCS), a noninvasive neuromodulatory method, may be a safe and potentially effective treatment, but conclusions have been limited by small-sample sizes and brief stimulation protocols. This double-blind randomized trial involving 100 older adults with mild-to-moderate AD examines effects of 6 months of at-home active tDCS or sham delivered over the dorsolateral prefrontal cortex. The primary outcome is global cognitive performance. Secondary outcomes include executive-control/spatial selective attention, functional neuroplasticity, depressive symptoms, quality of life and the durability of effects 3 months after the stimulation period. The results will provide evidence on the efficacy of multimonth at-home tDCS in the AD treatment. =Clinical trial identifier NCT04404153 (Clinicaltrials.gov).

Aim: To examine whether education adjusted cut-off points of the Thai version of the ACE-III improve diagnostic accuracy in the detection of mild cognitive impairment (MCI) and dementia. Materials & methods: There were 172 participants consisting of 70 normal controls, 49 people with MCI and 53 patients with dementia. Results: To screen for MCI, the adjusted for education method yielded greater accuracy for the area under the receiver operating characteristic curve (AuROC) than the unadjusted method (0.9-0.92 vs 0.86). For the detection of dementia, when applying the education correction, AuROC increased from 0.87 (unadjusted) to 0.91 for the education >6 group, but there was no improvement for education ≤6 group (AuROC 0.86). Conclusion: The use of adjusted cut-off score for education level could increase the diagnostic accuracy of the test.

Recently, the roles of inflammation and insulin resistance in neurodegeneration have become better appreciated. NE3107, an oral small molecule, blood-brain permeable anti-inflammatory insulin sensitizer that binds extracellular signal-regulated kinase, has been shown to selectively inhibit inflammation-driven ERK- and NF-κB-stimulated inflammatory mediators, including TNF-α, without inhibiting their homeostatic functions. We describe the rationale and design of NM101, the first randomized, multicenter Phase III clinical study to examine the safety and efficacy of 30 week treatment with NE3107 versus placebo in elderly adults with mild-to-moderate Alzheimer's disease. Patients (316) will be randomized in a 1:1 ratio. The co-primary end points measure cognitive function (ADAS Cog12), and functional and behavioral characteristics (ADCS CGIC). Trial registration number: NCT04669028 (Clinicaltrials.gov).

Multiple sclerosis (MS) is an inflammatory disease that causes chronic neurological disability in young adults. Modulation of sphingosine 1-phosphate (S1P) receptors, a group of receptors that, among other things, regulate egression of lymphocytes from lymph nodes, has proven to be effective in treating relapsing MS. Fingolimod, the first oral S1P receptor modulator, has demonstrated potent efficacy and tolerability, but can cause undesirable side effects due to its interaction with a wide range of S1P receptor subtypes. This review will focus on ozanimod, a more selective S1P receptor modulator, which has recently received approval for relapsing MS. We summarize ozanimod's mechanism of action, and efficacy and safety from clinical trials that demonstrate its utility as another treatment option for relapsing MS.