Current Neuropharmacology - Online First

Numerous studies have demonstrated that efgartigimod is effective in treating myasthenia gravis (MG) across various patient populations. However, there is limited evidence regarding its use in patients with new-onset acetylcholine receptor antibody-positive generalized MG (AChR-gMG). Therefore, this study aimed to investigate the real-world safety and effectiveness of efgartigimod in Chinese patients with new-onset anti-cholinergic receptor (AChR)- gMG.

This prospective study was conducted in 29 patients with new-onset AChR-gMG, with a three-month follow-up. The Myasthenia Gravis Activities of Daily Living (MG-ADL) score, Quantitative Myasthenia Gravis score, prednisone dose, laboratory data, and adverse events were assessed at every follow-up visit.

At 4, 8, and 12 weeks, the mean change in MG-ADL scores was 8.13  ±  3.66, 7.41  ±  4.22, and 6.37  ±  4.67, respectively. Compared with the baseline, 96% (28/29) of patients achieved an MG-ADL response (defined as a decrease of ≥2 points), with a mean response time of 0.81 ± 0.53 weeks (5.67 ± 3.71 days). After one cycle, 52% (15/29) of patients achieved minimal symptom expression (MSE), while 41% maintained MSE at 12 weeks. Moreover, 89% and 72% of MG-ADL responders sustained for 8 and 12 consecutive weeks, respectively. Additionally, patients with thymomatous MG exhibited a poorer response to efgartigimod and required two infusion cycles. All patients were able to reduce their daily steroid dose, and the mean daily prednisone dose decreased by 10.73 mg per day. The treatment was well tolerated, and a few mild adverse events were reported.

These results demonstrate the clinical significance of efgartigimod in patients with new-onset AChR-gMG, achieving rapid symptom relief and steroid reduction. Additionally, the potential of efgartigimod to serve as a bridge treatment, facilitating a steady transition to long-term conventional immunosuppressive therapy, was demonstrated. Due to limitations in this study, such as a small sample size, larger randomized controlled trials are needed to validate.

Our study showed that efgartigimod is clinically beneficial and offers rapid symptom control in patients with new-onset AChR-gMG. A more aggressive application of efgartigimod in combination with corticosteroids may lead to a smoother therapeutic transition, which will further maintain favorable conditions.

Exogenous melatonin (exo-MLT) is a sleep-promoting agent that modulates key sleep-wake neurotransmitters.

This scoping review analyzed 623 studies retrieved from PubMed/MEDLINE and ISI/Web of Science, applying PRISMA methodology to ensure rigorous inclusion criteria. After screening, 58 original research papers were analyzed for exo-MLT's effects on gamma-aminobutyric acid (GABA), serotonin, dopamine, glutamine, norepinephrine, epinephrine, orexin, acetylcholine, adenosine, glycine, galanin, and histamine.

We identified 20 studies on the GABAergic system, showing that exo-MLT enhances GABA activity through different mechanisms, promoting non-REM sleep and reducing stress-related hyperarousal. On serotonin, 16 studies revealed limited and variable effects depending on the dose and physiological conditions. Total 13 dopamine studies suggested that exo-MLT does not alter physiological dopamine turnover, restoring dopaminergic balance in pathological states. On the glutamatergic system, seven studies showed a compensatory role of exo-MLT on glutamate excitotoxicity. Six studies on norepinephrine highlighted exo-MLT's ability to regulate sympathetic activity. The orexinergic system was the focus of five studies, indicating exo-MLT's inhibitory action on orexinergic neurons, enhancing sleep quality and consolidation. Five studies investigated exo-MLT on the cholinergic system, revealing an enhancing effect on acetylcholine activity in physiological and pathophysiological conditions. Lastly, four studies exploring adenosine and glycine were inconclusive of the exo-MLT effect, while we could not find any data on histamine and galanin.

This review underscores exo-MLT's mechanisms beyond circadian regulation, offering therapeutic promise in sleep disorders associated with other neuropsychiatric conditions.

Exo-MLT’s interactions provide insights into its safety and non-addictive characteristics, supporting its integration into personalized sleep medicine.

This study investigates the relationship between National Cancer Institute Common Terminology Criteria (NCI-CTC) for grading bortezomib-induced peripheral neuropathy (BIPN) and objective motor/sensory nerve dysfunctions assessed by nerve conduction studies (NCS). It also evaluates the correlation between specific nerve conduction abnormalities and progression-free survival (PFS).

Thirty-three patients with multiple myeloma developing peripheral neuropathy during bortezomib treatment were enrolled. Participants were grouped based on NCI-CTC toxicity scores (< 2, n=17; ≥ 2, n=16). Comprehensive NCS were performed, assessing compound muscle action potentials (CMAP), motor conduction velocities (MCV), sensory nerve action potentials (SNAP), and sensory conduction velocities (SCV) across ulnar, median, tibial, peroneal, sural, and superficial peroneal nerves. Correlation analyses were used to examine the association between NCS parameters and PFS.

Patients with higher NCI-CTC grades (≥ 2) exhibited significant reductions in motor and sensory nerve conduction parameters. Notably, the peroneal nerve showed significant decreases in CMAP (p=0.0059) and MCV (p=0.0223). The superficial peroneal nerve displayed a significant reduction in SCV (p=0.0189). A strong positive correlation was found between median nerve SNAP and longer PFS (r=0.558, p=0.001).

The findings indicate that higher clinical grades of BIPN (NCI-CTC ≥ 2) are associated with objective neurophysiological evidence of worsened nerve function, with the peroneal nerve being particularly affected. The correlation between median nerve SNAP and PFS suggests that NCS parameters could potentially serve as prognostic markers in patients with BIPN.

Bortezomib-induced neurotoxicity leads to significant impairments in both motor and sensory nerve conduction. Median nerve SNAP shows promise as a predictor for PFS, underscoring the potential value of NCS in monitoring neurotoxicity and guiding clinical management in patients receiving bortezomib.

Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain tumor, characterized by poor prognosis. Moreover, cognitive impairment from the tumor and its treatments compromises patients' quality of life. Butyrylcholinesterase (BChE) inhibition enhances cognitive function. Notably, BCHE is overexpressed in GBM tissues; its downregulation suppresses tumor cell proliferation, migration, and invasion. This study aimed to identify a BChE inhibitor with dual functionality: anti-GBM efficacy and cognitive protection via modulation of neuroinflammation.

QY-69 was identified from an in-house BChE inhibitor library through cytotoxicity-based screening. Its anti-GBM effects were evaluated through colony formation, wound healing, and transwell assays. Orthotopic GBM mice were treated with QY-69 orally for 15 days. Tumor progression, cognitive function (Morris water maze), and neuroinflammation (microglia and astrocyte immunofluorescence) were analyzed.

QY-69 exhibited significant antiproliferative activity at micromolar concentrations. In vitro assays demonstrated significant inhibition of GBM cell growth, migration, and invasion. Behavioral impairment in mice was improved, and the activation of astrocytes and microglia in peritumoral tissues was reduced, indicating a decrease in neuroinflammation.

QY-69 demonstrated dual therapeutic potential in GBM by inhibiting tumor progression and alleviating cognitive impairment. However, its precise molecular mechanisms remain to be elucidated. Future research should employ transcriptomic and proteomic approaches to elucidate the molecular basis of its anti-GBM activity.

QY-69, a BChE inhibitor, exhibits potent anti-GBM activity and confers cognitive protection, positioning it as a promising dual-action therapeutic candidate. By inhibiting tumor progression and reducing neuroinflammation, it may enhance both survival and quality of life in GBM patients.

Maternal chronic immune and inflammatory conditions may predispose newborns to atypical developmental trajectories, identifying pregnancy as a key period for the etiopathogenesis of neurodevelopmental disorders. The possible long-term impact of maternal multiple sclerosis (MS) on the offspring’s cognitive and behavioral development and its pharmacological treatment during pregnancy is mostly unknown. This study aims to delineate the cognitive and behavioral profile of offsprings exposed to maternal MS, untreated or treated with Natalizumab throughout pregnancy, in comparison to a control group.

We retrospectively enrolled 39 children (23 males; 16 females; mean age 45.82 ± 35.46 months) exposed to maternal MS, untreated or treated with Natalizumab throughout pregnancy, and 36 children (24 males; 12 females, mean age 38.03 ± 21.52 months) of healthy mothers. All offspring underwent a standardized evaluation of their intellectual or developmental quotient, adaptive functioning, and behavioral issues, including symptoms of autism.

The clinical profile of the included offspring was characterized by an adequate cognitive profile and a good level of adaptive skills (MS offspring: Griffiths III mean total DQ (N = 30) 114.57; WISC-IV mean Full IQs (N= 9) 115.44; mean ABAS GAC 97.28/Control offspring: Griffiths III mean total DQ (N = 31) 105.42; WISC-IV mean Full IQs (N= 4) 119.25 ± 11.32; mean ABAS GAC 97.82 ± 21.4). Furthermore, no significant behavioural problems or autism symptoms emerged in the entire group, regardless of MS treatment.

Offspring's developmental and behavioral phenotypes do not appear to be influenced by maternal treatment with Natalizumab until late pregnancy, nor by maternal variables directly related to MS (age at the time of MS diagnosis, disease duration, and severity).