Search Results (190)

Antibodies are indispensable for protection against biological toxins and pathogens, yet their conventional liquid formulations impose severe constraints, including dosing inaccuracy caused by residual fluid remaining in the syringe and limited user convenience such as pain caused by fluid-induced tissue distension and nerve stimulation as well as instability in ambient temperature, and the requirement for low-temperature storage and logistics. These limitations critically impair rapid deployment during golden hour following acute exposure. Here, we report an antibody-integrated solid-to-gel microfilm—demonstrated with a 100 µg anti-BoNT/A dose—jet-printed and low-temperature dried directly onto metal needles for consistent, on-demand use. Upon intradermal insertion, the microfilm fully dissolves within 5 min, driven by hydration-induced swelling of a hyaluronic acid (HA) support layer and rapid release of the antibody. Time-resolved microscopy and UV–vis analysis showed a decrease in residual solid from 2.34 mm³ to 0 over 300 s, with a concomitant rise at 187 nm indicative of complete dissolution. The solid formulation maintained ambient-temperature stability for 3–6 months with pharmacokinetics comparable to conventional subcutaneous liquid injections. In a lethal BoNT/A challenge, treated mice achieved 100% survival for 12 days, whereas controls succumbed within 16 h. Full article

Botulinum toxin (BoNT) causes flaccid paralysis by blocking the release of neurotransmitters. BoNTs associate with neurotoxin-associated proteins to form medium and large progenitor toxin complexes. The large progenitor toxin complex serotype A-62A (L-PTC/A-62A) specifically targets intestinal M cells for invasion, whereas large progenitor toxin complex serotype B-Okra (L-PTC/B-Okra) is mainly taken up by enterocytes and exhibits higher toxicity via the oral route. Hemagglutinin (HA) is a neurotoxin-associated protein that promotes BoNT absorption from the intestine and has carbohydrate-binding and barrier-disrupting activities. In this study, we established an in vitro reconstitution and purification system for recombinant L-PTC/B-Okra and created a recombinant L-PTC/B-Okra mutant rL-PTC/B-KA with carbohydrate-binding activity but not barrier-disrupting activity. rL-PTC/B-KA showed significantly reduced oral toxicity. Our results demonstrate that the B-Okra toxin disrupts the epithelial barrier of enterocytes and exerts oral toxicity. Full article

The neurotoxin BoNT/B2 is the predominant Clostridium parabotulinum subtype in foodborne and infant botulism cases in Spain. This study characterizes a novel case of foodborne botulism in Spain caused by a dual-toxin A1(B5) strain. A 64-year-old male presented with acute, progressive flaccid paralysis including diplopia, dysphagia, and respiratory failure. Although botulism was not initially suspected, the patient recovered with supportive care and without antitoxin administration. Genomic characterization confirmed the presence of both bont/A1 and silent bont/B5 genes. The bont/A1 gene was associated with an orfX+ neurotoxin gene cluster, while the silent bont/B5 gene was in an ha+ cluster. Phylogenetic analysis of both bont/A1 and bont/B5 sequences showed 100% amino acid identity, respectively, to previously reported A1(B5) strains (e.g., CDC_69094, FE9504ACG). Multi-locus sequence typing (MLST) assigned the ST10, a genotype previously undetected in Spanish botulism cases, yet found in other European countries. This case highlights the importance of considering botulism in differential diagnosis due to its varied presentation and the significance of timely laboratory confirmation for effective management. The identification of this dual-toxin BoNT/A1(B5) orfX+/ha+ ST10 strain expands our understanding of C. botulinum epidemiology and genetic diversity in Spain. Full article

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN), leading to motor impairments and numerous non-motor manifestations, including anxiety. Notably, anxiety has been shown to exacerbate disease progression and hinder treatment outcomes in PD. Botulinum neurotoxin (BoNT), recognized for its ability to block excessive release of acetylcholine (ACh), has been shown to provide clinical effectiveness in managing motor symptoms. BoNT appears to enhance neuroregenerative plasticity and mitigate neuroinflammation through mechanisms speculated to extend beyond its classical mode of action. Nevertheless, reports on its potential anxiolytic and neuroprotective effects in PD remain limited. Aim: This study investigated the effect of BoNT on motor and anxiety-like behaviors in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Methods: The experimental animals were assessed for behavioral changes using the open field test (OFT), rotarod, pole test, light-dark box test (LDBT), and elevated plus maze (EPM). Immunohistochemistry was employed to enumerate tyrosine hydroxylase (TH)-positive dopaminergic neurons and ionized calcium-binding adapter molecule (Iba)-1 expressing microglia in SN. Results: BoNT treatment markedly alleviated motor deficits and anxiety. Quantification of TH- and Iba-1-positive cells revealed that BoNT promotes neuroprotection and minimizes microglial burden in the SN of the PD model. Conclusions: The outcome of the study represents the anxiolytic, neuroprotective, and microglial modulatory potentials of BoNT in PD, supporting its therapeutic promise beyond the management of motor symptoms. Given its multifaceted properties, BoNT can be considered a potential therapeutic candidate for PD and other neurological disorders. Full article

Background: The primary effect of Botulinum toxin (BoNT) is to cause weakness in the injected muscles by inhibiting the release of acetyl choline from presynaptic nerve terminals. Its effect on sensorimotor integration (SMI) has largely been confined to small studies. The aim of this review is to highlight effect of BoNT on SMI in the context of Parkinson’s disease (PD), Cervical dystonia (CD), and Writer’s cramp (WC). Methods: Using keywords “Botulinum toxin” and “sensorimotor integration” or “Freezing of gait (FOG)” or ‘Tremor”or “Cervical dystonia” or “Parkinson’s disease”, or “Writer’s cramp”, PubMed database was searched for relevant articles supporting our view. The abstracts of all resultant articles (case reports, case series, randomized trials, observational studies) were reviewed to look for evidence of effects of botulinum toxin on SMI. The relevant articles were charted in excel sheet for further full text review. Results: In FOG, chronic BoNT injections may alter central motor patterns with inclusion of alternative striatal systems, cerebellum, and its connections. In tremor, the afferent proprioceptive input may be modified with reduction of intracortical facilitation and increment of intracortical inhibition. In CD, BoNT can restore disorganized cortical somatotrophy, the key pathophysiology behind cervical dystonia. Similarly, in WC, both the deficient sensory system and abnormal reorganization of the sensorimotor cortex may be altered following chronic BoNT injections. Conclusions: There is preliminary evidence that BoNT may modulate SMI in PD, CD, and WC by altering inputs from the muscle spindles in short term and modifying circuits/particular anatomic cerebral cortices in the long term. Properly conducted randomized trials comparing BoNT with placebo or prospective large-scale studies to look for effect on various surrogate markers reflective of changes in SMI should be the next step to confirm these findings. Targeting the system of afferents like spindles and golgi tendon organs in muscles may be a better way of injecting BoNT, with lower amounts of toxin needed and potential for lesser side-effects like weakness and atrophy. However, this needs to be proven in controlled trials. Full article

Purpose: Detrusor sphincter dyssynergia (DSD), a common lower urinary tract condition in patients with suprasacral spinal cord injury (SCI), can lead to urological complications and reduced quality of life. Urethral sphincter botulinum toxin A (BoNT-A) injection has been used to promote spontaneous voiding, albeit with limited success. This study aimed to identify predictive factors for treatment success. Methods: This retrospective analysis included 207 patients (157 males and 50 females) with chronic SCI and varying DSD grades treated with urethral sphincter BoNT-A injection. Each received 100 U of onabotulinumtoxinA via transurethral sphincter injection. The primary outcome was voiding efficiency (VE) and symptom improvement, assessed via global response evaluation 3 months post-treatment. Baseline videourodynamic parameters were used to predict success. Results: Successful outcomes were observed in 33.8% of patients. These patients were older and had higher voiding pressure, maximum flow rate (Qmax), voided volume, bladder contractility index, and VE, as well as lower post-void residual (PVR) volume and bladder outlet obstruction index. Patients with SCI and DSD grade 1 had the highest success rate (65.7%) compared to those with DSD grade 2 (14.3%) or 3 (7.1%). Patients with DSD grade 3 had the highest failure rate (55.8%). Multivariate analysis showed that higher Qmax and lower PVR significantly predicted success, consistent with lower DSD grades. Conclusion: Grade 1 DSD, higher Qmax, and lower PVR were associated with higher success after urethral BoNT-A injection, whereas grade 3 DSD predicted failure. Thus, careful patient selection is essential for effective DSD treatment with urethral BoNT-A injection. Full article

Background: In recent years, botulinum toxin (BoNT) has been increasingly employed not only as a corrective aesthetic intervention but also as a proactive strategy to delay the visible signs of facial aging. This systematic review aims to evaluate the scientific evidence supporting the preventive role of BoNT in facial aging, focusing on its long-term effects, mechanisms of action, and clinical outcomes when used in younger, pre-symptomatic populations. Methods: A systematic literature search was conducted across PubMed, Scopus, and Web of Science databases. Inclusion criteria encompassed clinical trials and observational studies addressing the use of BoNT for proactive aesthetic strategies. Results: Evidence suggests that early BoNT application may reduce muscle hyperactivity, delay the formation of dynamic wrinkles, and minimize the development of static lines over time. Histological studies indicate a potential remodeling effect on dermal collagen. However, data remain heterogeneous, and long-term safety and efficacy outcomes are not yet fully established. Conclusion: Preventive BoNT injections represent a promising tool in the proactive management of facial aging. Further longitudinal, high-quality studies are needed to substantiate its role within evidence-based aesthetic protocols. Full article

Tremor, an oscillatory movement disorder, is commonly encountered in clinical practice in the setting of a variety of etiologies, such as essential tremor and Parkinson’s disease. Despite its high prevalence, treatment options are somewhat limited. Oral medications are often ineffective or limited by side effects, and other treatments, such as deep brain stimulation, are more invasive and costly. Botulinum toxin (BoNT) injections are a well-established therapy in the treatment of dystonia, but its use in the treatment of tremors has not been fully explored. In this review, we discuss the available randomized controlled trials and open-label evidence for the use of BoNT in various tremor etiologies, as well as its injection techniques. While essential tremor is the most studied condition, other tremor etiologies and tremor types such as Parkinson’s disease, head tremor, voice tremor, proximal tremor, and tremor due to dystonia and multiple sclerosis have been studied as well. Botulinum toxin injections have provided evidence of significant benefit in outcomes in several trials among these indications, but transient weakness remains a common adverse effect. There is a paucity of well-designed trials as many published studies have relatively small cohorts and results are additionally limited by heterogenous outcome measures, dosages, muscle selection techniques and methods of injection. Full article

The efficacy of botulinum toxin A (BoNT) in alleviating motor symptoms of cervical dystonia (CD) has been well established, and it is the treatment of choice in this disease. Lately, the effect of BoNT on non-motor symptoms (NMS) such as cognitive function, depression, anxiety, pain, and sleep disturbance has been observed in patients with CD. A comprehensive clinical and functional assessment of motor (dystonia severity, gait) and non-motor symptoms (cognitive functions, depression, anxiety, sleep, and pain) has been performed in a total of 34 adult patients with cervical dystonia before and after BoNT treatment. Results have also been compared to a control group. Significant improvements in the scales assessing dystonia severity have been observed, which is in line with previous studies on the effect of BoNT on motor symptoms in dystonia. Interestingly, the results also clearly indicate that BoNT has a positive effect on NMS. Among the studied non-motor domains, depression and cognitive functions improved the most after the treatment procedure. The study highlights the potential of BoNT to positively influence non-motor symptoms in patients with cervical dystonia, although its effect on various NMS is not equal. Full article

Orofacial pain encompasses a spectrum of disorders ranging from musculoskeletal disorders, such as myofascial pain, and temporomandibular disorders to neuropathic situations, such as trigeminal neuralgia and painful post-traumatic trigeminal neuropathy, and neurovascular pain such as orofacial migraine and cluster orofacial pain. Each require tailored prophylactic pharmacotherapy, such as carbamazepine, gabapentin, pregabalin, amitriptyline, metoprolol, and topiramate. Yet a substantial subset of patients remains refractory. Botulinum toxin type A (BoNT-A) has demonstrated growing efficacy in the treatment of multiple forms of orofacial pain, which covers the whole range of these disorders. We describe the analgesic properties of BoNT-A for each of the three following orofacial pain disorders: neuropathic, myofascial, and neurovascular. Then, we conclude with a section on the neuromodulatory mechanisms of BoNT-A. This lays the basis for the generation of a hypothesis for the segmental therapeutic action of BoNT-A on the whole range of orofacial pain disorders. In addition, the advantage of BoNT-A for providing a safe sustained effect after a single application for chronic pain prophylaxis is discussed, as opposed to the daily use of current conventional prophylactic medications. Finally, we summarize the clinical applications of BoNT-A for chronic orofacial pain therapy. Full article

The use of Botulinum Neurotoxin A (BoNT/A) to treat peripheral neuropathic pain from nerve injury has garnered interest for its long-lasting effects and safety. This study examined the effects of IncobotulinumtoxinA (Inco/A), a BoNT/A variant without accessory proteins, on nerve regeneration in rats using the chronic constriction injury (CCI) model. Inco/A was administered perineurally at two time points: on days 0 and 21 post CCI. Functional and histological assessments were conducted to evaluate the effect of Inco/A on nerve regeneration. Sciatic Functional Index (SFI) measurements and Compound Muscle Action Potential (CMAP) recordings were conducted at different time points following CCI. Inco/A-treated animals exhibited a 65% improved SFI and 22% reduction in CMAP onset latencies compared to the vehicle-treated group, suggesting accelerated functional nerve recovery. Tissue analysis revealed enhanced remyelination in Inco/A-treated animals and 60% reduction in CGRP and double S100β signal expression compared to controls. Strikingly, 30% reduced immune cell influx into the injury site was observed following Inco/A treatment, suggesting that its anti-inflammatory effect contributes to nerve regeneration. These findings show that two injections of Inco/A promote functional recovery by enhancing neuroregeneration and modulating inflammatory processes, supporting the hypothesis that Inco/A has a neuroprotective and restorative role in nerve injury conditions. Full article

While surgical procedure has been considered as the golden standard treatment for spasmodic entropion, Botulinum Neurotoxin A can be indicated in the treatment of spasmodic entropion for fragile elderly patients. This retrospective cohort study included 50 outdoor patients treated for spasmodic entropion, for whom palpebral surgery was recused. The intent of the present study was to describe an alternative outdoor treatment, to detail precisely the Botulinum Neurotoxin (BoNT) treatment pattern, the dosage of BoNT needed, the frequency of re-injection, the efficiency and the complications encountered. Fifty patients, 87.9 years old in average (±14.3) have been injected with BoNT. The average total dosage of BoNT is 7.62 ± 1.38 units of Incobotulinum, 10.2 ± 1.03 units of Onabotulinum and 17.2 ± 1.33 Speywood-units of Abobotulinum. Spasmodic entropion resolved in 3 ± 2 days after the BT injection. The average for re-injection is every 4.25 ± 1.30 months. By adjusting age and total dose, we have not been able to show any statistically significant relationship between time needed for re-injection and type of botulinum toxin A (p = 0.59). Patients with spasmodic entropion have responded significantly to BoNT injection. No systemic complications have been reported in this study. BoNT treatment is safe and effective for fragile elderly patients with spasmodic entropion and can be proposed instead of surgery or while waiting for their procedure. Full article

Background: Botulinum toxin type A (BoNT/A) is widely used in both clinical and aesthetic settings to induce temporary neuromuscular paralysis by inhibiting acetylcholine release. Although generally regarded as safe and effective, complications such as iatrogenic ptosis or facial asymmetry may occur and persist for several weeks or even months, with no standardized method currently available to accelerate recovery. Objective: This article explores the hypothesis that photobiomodulation (PBM)—a non-invasive modality recognized for its neuroregenerative potential—may facilitate the reversal of BoNT/A-induced neuromuscular blockade. Discussion: PBM enhances mitochondrial activity by stimulating cytochrome c oxidase in nerve and muscle tissues, thereby increasing ATP production and modulating intracellular signaling pathways associated with neuroplasticity, cell survival, and synaptogenesis. Preclinical studies have demonstrated that PBM can upregulate neurotrophic factors (e.g., BDNF, NGF), enhance SNAP-25 expression, and promote structural remodeling of neurons in both young and aged brains. These mechanisms are biologically consistent with the regenerative processes required for recovery from BoNT/A-induced effects. While controlled clinical trials for this specific application are currently lacking, anecdotal clinical reports suggest that PBM may accelerate functional recovery in cases of BoNT/A-related complications. Conclusions: Although this approach has not yet been tested in clinical trials, we propose that photobiomodulation may hypothetically serve as a supportive strategy to promote neuromuscular recovery in patients experiencing adverse effects from BoNT/A. This hypothesis is grounded in robust preclinical evidence but requires validation through translational and clinical research. Full article

Botulinum neurotoxins (BoNTs) are known to inhibit synaptic transmission by targeting SNARE proteins, but their selectivity toward central excitatory and inhibitory pathways is not yet fully understood. In this study, the interaction of serotypes A (BoNT/A) and B (BoNT/B) with the glutamatergic and GABAergic systems has been investigated using a pharmacological approach in an animal model of inflammatory pain, i.e., the formalin test in mice. BoNTs were administered intracerebroventricularly, three days before testing, followed 15 min before testing by systemic administration of sub-analgesic doses of MK801, an NMDA receptor antagonist, or muscimol, a GABA_A receptor agonist. BoNT/A reduced the second phase of the formalin test without affecting both the first phase and the interphase, suggesting a selective action on excitatory glutamatergic circuits while sparing GABAergic inhibition. Co-administration of MK801 with BoNT/A did not enhance analgesia, and muscimol did not further reduce interphase, confirming preserved GABAergic transmission. In contrast, BoNT/B abolished the interphase, consistent with impaired GABA release. Co-administration of MK801 or muscimol with BoNT/B restored the interphase, indicating compensatory rebalancing of excitatory-inhibitory networks. These results demonstrate that BoNT/A and BoNT/B exert distinct effects on central neurotransmission and support the hypothesis that BoNT/A preferentially targets excitatory synapses, while BoNT/B targets inhibitory synapses. This work contributes to a deeper understanding of anti-inflammatory mechanisms of BoNTs and their selective interaction with central pain pathways. Full article

Spasticity is a persistent and debilitating consequence of stroke and effective rehabilitation is a healthcare priority. Botulinum neurotoxin A (BoNT-A) with supportive therapy has increasingly been embedded within clinical practice for treatment of post-stroke spasticity. But the evidence for this approach has hitherto been limited to the findings of a limited number of small trials. The InTENSE trial was undertaken specifically to provide high-quality clinical trial evidence focusing on the effect of BoNT-A and adjunctive therapy on upper limb spasticity. While the clinical trial did not detect a significant impact upon clinical outcomes, there remains a need to evaluate any impact on the broader use of healthcare resources and overall cost-effectiveness. A detailed cost–utility analysis of the InTENSE trial was undertaken. The costs over the 12-month follow-up period were compared with quality-adjusted life years (QALY) gained using utilities generated from the EQ-5D three level (EQ-5D-3L) instrument. There were no significant differences in QALY gained between the intervention and control groups identified, or in the majority of health and community care costs. The Incremental Cost-Effectiveness Ratio per QALY gained was estimated at AU $63,947.11 (Australian dollars), which is well above accepted thresholds for cost-effectiveness in Australia. The study was unable to identify evidence for the cost-effectiveness of treatment approaches combining BoNT-A with adjunctive therapy. Full article