OBJECTIVE:The Col-Cap classification for cervical dystonia (CD) has been proposed to optimize treatment strategies with botulinum toxin type A (BTX-A). Although this concept has been used for 15 years, the efficacy of BTX-A in various CD patterns remains unclear. The present study compared the efficacy of BTX-A, aided by single-photon emission computed tomography (SPECT) and electromyography (EMG), in various CD patterns. METHODS:CD patients who underwent SPECT scans to detect dystonic muscles were included. Candidate muscles were first selected based on clinical evaluation and abnormal radioactivity on SPECT imaging. All patients were injected under the guidance of EMG, and only candidate muscles with positive EMGs were injected. The efficacy of BTX-A was assessed via the subjective clinical improvement rate and the reduction in the Tsui score at four weeks after injection. RESULTS:The study enrolled 252 patients. The subjective improvement rates were 63.5%±20.6% for simple types and 59.9%± 22.2% for complex types, and this difference was not significant (p=0.247). The reduction rates of the Tsui score did not differ between the simple type (52.4%±24.2%) and the complex type (49.6%±23.6%, p=0.556). Moreover, clinical improvement rates did not significantly differ within each group of simple subtypes, complex subtypes, or patients with different types of tremors (p>0.05). CONCLUSION:The efficacy of BTX-A treatment was comparable in different CD patterns because of the appropriate selection of dystonic muscles via SPECT and EMG. Therefore, employing multifaceted approaches to identify dystonic muscles can yield favorable outcomes, even in complex cases.

BACKGROUND:The safety and effectiveness of deep brain stimulation of the subthalamic nucleus (STN-DBS) for the treatment of dystonia lack high-level evidence-based medical support. This study aimed to clarify the efficacy and safety of STN-DBS and perform a post hoc analysis comparing it with DBS of the internal globus pallidus (GPi-DBS). METHODS:This multicentre, randomised, double-blind, controlled trial included 67 patients aged 6-60 years old diagnosed with genetic or idiopathic isolated generalised or segmental dystonia. They were enrolled from seven hospitals in China and randomly assigned to undergo GPi-DBS or STN-DBS. After surgery, they were randomised to receive either neurostimulation or sham stimulation for 3 months. At the 3-month follow-up, neurostimulation was also initiated in the sham stimulation group, and all patients were followed up for more than 3 years after treatment. The primary outcome was the Burke-Fahn-Marsden Dystonia Rating Scale movement (BFMDRS-M) score. RESULTS:In the STN group, the neurostimulation subgroup exhibited significant improvement (p<0.001), which is also superior to the sham stimulation subgroup (p=0.028) at 3-month follow-up. At the 6-month and >3-year follow-ups, all patients receiving STN-DBS showed a significant improvement in BFMDRS-M scores (p<0.001). Further post hoc analysis revealed that both STN-DBS and GPi-DBS could produce similar therapeutic effects on motor symptoms (P6 months=0.865, P>3 years=0.905). There were no ongoing serious adverse events throughout the study. CONCLUSIONS:For isolated generalised and segmental dystonia patients, the STN is a selectable DBS target with ensured safety and efficacy. STN-DBS and GPi-DBS may achieve comparable therapeutic effects on motor symptoms. TRIAL REGISTRATION NUMBER:NCT03017586.

OBJECTIVE:This study aimed to assess the efficacy and safety of botulinum toxin type A (BTX-A) injection near the stylomastoid foramen for tinnitus in patients with hemifacial spasm (HFS). STUDY DESIGN:Retrospective study from 2011 to 2024. SETTING:Tongji Hospital affiliated to Tongji University in Shanghai, China. PATIENTS:Patients with HFS combined with tinnitus. INTERVENTION:BTX-A injection near the stylomastoid foramen. MAIN OUTCOME MEASURES:The efficacy of BTX-A was assessed based on subjective improvement reported by patients after 1 month. Adverse events were also documented. RESULTS:A total of 869 HFS patients were analyzed, including 122 with tinnitus. Among the 122 patients with tinnitus, 110 received BTX-A injections near the stylomastoid foramen, and complete follow-up data were available for 105 of them. The 3.75 U group showed a higher improvement rate (69.2 ± 14.3%) compared with the 2.5 U group (46.3 ± 25.0%, p < 0.05). The majority received a 5 U dose, with a significantly higher improvement rate (76.9 ± 15.1%) compared with the 2.5 U group ( p < 0.01). All reported adverse events were related to routine injection sites and were mild, requiring no special treatment. No adverse events related to BTX-A injection near the stylomastoid foramen were reported. CONCLUSION:In patients with HFS-associated tinnitus, additional injection of 5 U BTX-A near the stylomastoid foramen, targeting the stapedius muscle, proved to be an effective therapy with minimal adverse effects.

It is very crucial to investigate key molecules that are involved in myelination to gain an understanding of brain development and injury. We have reported for the first time that pathogenic variants p.R477H and p.P505S in KARS, which encodes lysyl-tRNA synthetase (LysRS), cause leukoencephalopathy with progressive cognitive impairment in humans. The role and action mechanisms of KARS in brain myelination during development are unknown. Here, we first generated Kars knock-in mouse models through the CRISPR-Cas9 system. Kars knock-in mice displayed significant cognitive deficits. These mice also showed significantly reduced myelin density and content, as well as significantly decreased myelin thickness during development. In addition, Kars mutations significantly induced oligodendrocyte differentiation arrest and reduction in the brain white matter of mice. Mechanically, oligodendrocytes' significantly imbalanced expression of differentiation regulators and increased capase-3-mediated apoptosis were observed in the brain white matter of Kars knock-in mice. Furthermore, Kars mutations significantly reduced the aminoacylation and steady-state level of mitochondrial tRNA(Lys) and decreased the protein expression of subunits of oxidative phosphorylation complexes in the brain white matter. Kars knock-in mice showed decreased activity of complex IV and significantly reduced ATP production and increased reactive oxygen species in the brain white matter. Significantly increased percentages of abnormal mitochondria and mitochondrion area were observed in the oligodendrocytes of Kars knock-in mouse brain. Finally, melatonin (a mitochondrion protectant) significantly attenuated mitochondrion and oligodendrocyte deficiency in the brain white matter of Kars(R504H/P532S )mice. The mice treated with melatonin also showed significantly restored myelination and cognitive function. Our study first establishes Kars knock-in mammal models of leukoencephalopathy and cognitive impairment and indicates important roles of KARS in the regulation of mitochondria, oligodendrocyte differentiation and survival, and myelination during brain development and application prospects of melatonin in KARS (or even aaRS)-related diseases.

[This retracts the article DOI: 10.3892/etm.2020.8510.].

OBJECTIVE:Blepharospasm (BSP), focal dystonia with the highest risk of spread, lacks clear understanding of early spreading risk factors and objective prognostic indicators. We aimed to identify these risk factors through clinical and electrophysiological assessments, and to establish a predictive model for dystonic spread in BSP. METHODS:We prospectively followed BSP patients for 4 years, collecting data on dystonic spread, and conducting electrophysiological evaluations. The blink reflex, masseter inhibitory reflex, and trigeminal somatosensory evoked potential were assessed. Univariable and multivariable Cox proportional hazard regression models were used to assess clinical characteristics associated with BSP dystonic spread. A predictive model was constructed using a nomogram, and performance of the model was evaluated using the area under the receiver operating characteristic curve. RESULTS:A total of 136 enrolled participants (mean age 56.34 years) completed a 4-year follow-up. Among them, 62 patients (45.6%) showed spread to other body regions. Multivariable Cox regression analysis showed that a high Hamilton Anxiety Scale score (hazard ratio 1.19, 95% confidence interval 1.13-1.25, p < 0.001), prolonged trigeminal somatosensory evoked potential mandibular branch P1-N2 peak interval (hazard ratio 1.11, 95% confidence interval 1.02-1.21, p = 0.017), and elevated trigeminal somatosensory evoked potential mandibular branch P1-N2 peak amplitude (hazard ratio 1.26, 95% confidence interval 1.12-1.41, p < 0.001) were independent risk factors for BSP dystonic spread within 4 years. Combining these factors, the predictive models demonstrated excellent discriminative ability, with the receiver operating characteristic curve score being 0.797, 0.790, 0.847, and 0.820 at 1, 2, 3 and 4 years after enrollment, respectively. INTERPRETATION:We established a predictive model with significant value for anticipating dystonic spread in BSP, offering crucial evidence. These findings contribute essential insights into the early clinical identification of the development and evolution of BSP diseases. ANN NEUROL 2024;96:747-757.

When spontaneous cervical spinal epidural hematoma (SCEH) presents with hemiparesis, it can be misdiagnosed with ischemic stroke (IS), and the treatment of IS such as thrombolysis may deteriorate the symptoms of patients with SCEH, leading to worse sequelae or even death. We reported 3 SCEH patients who were initially suspected as IS in our center between Jun 2020 and April 2022 and analyzed their clinical characteristics together with 48 patients reported in the literature from Jan 1995 to April 2022. Two of the 3 SCEH patients had neck symptoms, while none of them presented cranial nerve symptoms. Cranial computed tomography (CT) scans were negative; however, abnormal signals in the cervical spinal canal were observed during cranial computed tomography angiography (CTA) and subsequent cervical CT confirmed the diagnosis of SCEH. All of them avoid mistreatment with recombinant tissue plasminogen activator (rt-PA). Subsequently, we analyzed the clinical characteristics of a total of 51 patients. Thirteen of them developed symptoms during activity. Neck pain was an important sign of SCEH because 35 patients had neck pain or neck discomfort. Sensory impairment was reported in a small proportion of patients (11/51), which varied a lot in the patients. Some special manifestations highly suggested spinal cord lesions and provided evidence for the early differential diagnosis of SCEH and stroke, but the incidence of which was quite low: ipsilateral Horner syndrome in 2 patients, Brown-Séquard syndrome in 2 cases, and Lhermitte’s sign in 1 case. Only a minority (8/51) of the patients were correctly diagnosed at the emergency unit using cervical CT. Six patients were correctly diagnosed when performing CTA. A large portion of the cases (21/51) were first misdiagnosed as IS, but no responsible lesions were found on cranial magnetic resonance imaging (MRI), and subsequent cervical MRI confirmed the diagnosis. Sixteen patients were diagnosed with SCEH after the deterioration of symptoms. A total of 13 patients received rt-PA, and 10 of them had symptoms aggravation after thrombolysis. For patients with acute onset of hemiparesis but without cranial nerve symptoms, especially those accompanied by clinical features such as neck pain, ipsilateral Horner syndrome, Brown-Séquard syndrome, and Lhermitte’s sign, SCEH should be highly suspected rather than stroke. Careful differential diagnosis should be performed with a comprehensive medical history and thorough physical examination. Cervical CT scan is a reasonable choice for quick differential diagnosis prior to administering potentially harmful therapy, especially rt-PA.

Introduction The pedunculopontine nucleus (PPTg) is a vital interface between the basal ganglia and cerebellum, participating in modulation of the locomotion and muscle tone. Pathological changes of the PPTg have been reported in patients and animal models of dystonia, while its effect and mechanism on the phenotyping of dystonia is still unknown. Methods In this study, a series of behavioral tests focusing on the specific deficits of dystonia were conducted for mice with bilateral and unilateral PPTg excitotoxic lesion, including the dystonia-like movements evaluation, different types of sensory-motor integrations, explorative behaviors and gait. In addition, neural dysfunctions including apoptosis, neuroinflammation, neurodegeneration and neural activation of PPTg-related motor areas in the basal ganglia, reticular formations and cerebellum were also explored. Results Both bilateral and unilateral lesion of the PPTg elicited dystonia-like behaviors featured by the hyperactivity of the hindlimb flexors. Moreover, proprioceptive and auditory sensory-motor integrations were impaired in bilaterally lesioned mice, while no overt alterations were found for the tactile sensory-motor integration, explorative behaviors and gait. Similar but milder behavioral deficits were found in the unilaterally lesioned mice, with an effective compensation was observed for the auditory sensory-motor integration. Histologically, no neural loss, apoptosis, neuroinflammation and neurodegeneration were found in the substantia nigra pars compacta and caudate putamen (CPu) following PPTg lesion, while reduced neural activity was found in the dorsolateral part of the CPu and striatal indirect pathway-related structures including subthalamic nucleus, globus pallidus internus and substantia nigra pars reticular. Moreover, the neural activity was decreased for the reticular formations such as pontine reticular nucleus, parvicellular reticular nucleus and gigantocellular reticular nucleus, while deep cerebellar nuclei were spared. Conclusion In conclusion, lesion of the PPTg could elicit dystonia-like behaviors through its effect on the balance of the striatal pathways and the reticular formations.

Introduction:Retroform cervical dystonia (RCD), which includes retrocaput and retrocollis, is a rare form of cervical dystonia. Few reports have been published on RCD. The present study aimed to characterize the target muscles involved in RCD and the efficacy of botulinum toxin type A (BTX-A) injection.Methods:Patients with consecutive cervical dystonia with RCD as the most problematic feature were retrospectively analyzed over a 10-year period. Target muscles were screened and confirmed based on clinical evaluation, single-photon emission computed tomography, and electromyography. In addition, efficacy and adverse events following BTX-A injection in patients with RCD were evaluated.Results:A total of 34 patients with RCD were included, 18 of whom presented with retrocaput and 16 with retrocollis. The most frequently injected muscles in RCD were splenius capitis (SPCa, 97.1%) and semispinalis capitis (SSCa, 97.1%), followed by levator scapulae (LS, 50.0%), rectus capitis posterior major (RCPM, 47.1%), trapezius (TPZ, 41.2%), and sternocleidomastoid muscle (SCM, 41.2%). Besides cervical muscles, the erector spinae was also injected in 17.6% of patients. Most muscles were predominantly bilaterally injected. The injection schemes of retrocaput and retrocollis were similar, possibly because in patients with retrocollis, retrocaput was often combined. BTX-A injection achieved a satisfactory therapeutic effect in RCD, with an average symptom relief rate of 69.0 ± 16.7%. Mild dysphagia (17.6%) and posterior cervical muscle weakness (17.6%) were the most common adverse events.Conclusion:SPCa, SSCa, LS, RCPM, LS, and SCM were commonly and often bilaterally injected in RCD. Patients with RCD could achieve satisfactory symptom relief after BTX-A injection.

Torticaput is the most common primary form of cervical dystonia (CD). Obliquus capitis inferior (OCI) plays a major role in ipsilateral rotation of the head. The present study aimed to use single-photon emission computed tomography (SPECT/CT) to determine the involvement of OCI in torticaput and in torticaput associated with no–no tremor. We retrospectively analyzed the SPECT/CT images of 60 patients with torticaput as the main abnormal posture and ranked the affected muscles. The affected muscles in patients with no–no tremor were also ranked. The correlation between the radioactivity of OCI and the thickness of OCI measured by ultrasonography was analyzed. The agreement between SPECT/CT and electromyography in detecting OCI was also analyzed. After sternocleidomastoid muscle (81.7%), OCI was the second most affected muscle (70.0%) in torticaput, followed by splenius capitis (63.3%). In 23 patients with no–no tremor, OCI (78.3%) and sternocleidomastoid muscle (78.3%) were the most frequently affected muscles, followed by splenius capitis (69.6%). Furthermore, bilateral muscle involvement was commonly seen in patients with no–no tremor, especially for OCI (12/23) and sternocleidomastoid muscle (11/23). A positive correlation was found between the radioactivity and thickness of OCI (r = 0.330, P < 0.001). The total agreement rate between SPECT/CT and electromyography in the diagnosis of OCI excitement was 94.0%, with kappa value = 0.866 (P < 0.001). OCI plays a critical role in torticaput and no–no tremor. SPECT/CT could be a practical tool to help clinicians detect abnormally excited OCI.

Being a major component of the midbrain locomotion region, the pedunculopontine nucleus (PPN) is known to have various connections with the basal ganglia, the cerebral cortex, thalamus, and motor regions of the brainstem and spinal cord. Functionally, the PPN is associated with muscle tone control and locomotion modulation, including motor initiation, rhythm and speed. In addition to its motor functions, the PPN also contribute to level of arousal, attention, memory and learning. Recent studies have revealed neuropathologic deficits in the PPN in both patients and animal models of dystonia, and deep brain stimulation of the PPN also showed alleviation of axial dystonia in patients of Parkinson's disease. These findings indicate that the PPN might play an important role in the development of dystonia. Moreover, with increasing preclinical evidences showed presence of dystonia-like behaviors, muscle tone changes, impaired cognitive functions and sleep following lesion or neuromodulation of the PPN, it is assumed that the pathological changes of the PPN might contribute to both motor and non-motor manifestations of dystonia. In this review, we aim to summarize the involvement of the PPN in dystonia based on the current preclinical and clinical evidences. Moreover, potential mechanisms for its contributions to the manifestation of dystonia is also discussed base on the dystonia-related basal ganglia-cerebello-thalamo-cortical circuit, providing fundamental insight into the targeting of the PPN for the treatment of dystonia in the future.

颈部肌张力障碍是最常见的局灶性肌张力障碍之一,肉毒毒素注射为一线治疗方法.能否正确识别与筛选责任痉挛肌肉是影响疗效的重要因素之一.目前临床上主要通过视诊和触诊异常肥大、僵硬或者疼痛的肌肉,并根据异常运动模式来判断责任肌肉.越来越多的研究探索辅助检查对痉挛责任肌肉的识别和筛选,主要包括运动学分析、EMG、超声及影像学检查.本文将对现有评估技术的有效性以及优缺点进行综述,为临床医生选择适合的评估工具提供思路.

Background: Although single-photon emission computed tomography (SPECT/CT) could help to predetermine dystonic muscles in patients with cervical dystonia (CD), its efficacy in aiding botulinum toxin injection is undetermined. This randomized, double-blinded study aimed to assess the efficacy of SPECT/CT aided botulinum toxin injection in CD. Methods: Patients were randomized into study group (candidate muscles selected by SPECT/CT and clinical evaluation) or control group (clinical evaluation). Follow-ups were done at two weeks (T1), one (T2), three (T3) and six months (T4). The primary outcomes included symptom improvement assessed using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui score at T2. Results: A total of 122 patients were enrolled and 108 patients accomplished the study. For primary outcomes, the study group had significantly better symptom improvement at T2 (TWSTRS: beta,-4.86 [95%CI-9.40 to-0.32; P = 0.036]; Tsui: beta,-1.65 [95%CI-2.77 to-0.54; P = 0.004]). For secondary outcomes, the study group also showed better outcomes at T1 (TWSTRS: beta,-6.33 [95%CI-10.17 to-2.49; P = 0.001]; Tsui: beta,-1.42 [95%CI-2.48 to-0.37; P = 0.008]) and T3 (TWSTRS: beta,-6.05 [95%CI-11.09 to-1.01; P = 0.019]; Tsui: beta,-1.24 [95% CI-2.40 to-0.08; P = 0.037]). The interval of re-injection was significantly longer in the study group than the control group (159.1 +/- 28.6 versus 141.8 +/- 51.0 days, P = 0.032). Conclusions: SPECT/CT could improve the efficacy of botulinum toxin in CD. It could become a useful tool to aid botulinum toxin injection.

In 1997, lanbotulinumtoxinA (LAN) was introduced in China. It is now available in Asia, Latin America and Eastern Europe under various brand names including Hengli®, Lantox®, Prosigne®, Lanzox®, Redux®, Liftox®, HBTX-A and CBTX-A. The literature on LAN is mostly published in Chinese language, restricting its international accessibility. We, therefore, wanted to generate a complete English bibliography of all LAN publications and then use it for a comprehensive formalised literature review. Altogether, 379 LAN publications (322 in Chinese and 57 in English) were retrieved from PubMed and Science and Technology Paper Citation Database. Indications covered are motor (257), glandular (16), pain (32) and aesthetics (48). Topics are neurological (250), aesthetic (48), paediatric (38), ophthalmological (18), urological (9), methodological (6), gastroenterological (5), ear, nose and throat (4) and surgical (1). Seventy-one publications are randomised controlled trials, forty-one publications are interventional studies and observational studies, fifteen publications are case studies, eighteen publications are reviews, and two publications are guidelines. LAN publications cover all relevant topics of BT therapy throughout a period of more than 20 years. This constitutes a publication basis resembling those of other BT drugs. None of the LAN publications presents data contradictory to those generated with other BT type-A drugs. LAN seems to have a similar efficacy and safety features when compared to onabotulinumtoxinA using a 1:1 LAN– onabotulinumtoxinA conversion ratio. Large controlled multicentre studies will become necessary for LAN’s registrations in Europe and North America.

BACKGROUND:The relationship between brain abnormalities and phenotypic characteristics in cervical dystonia (CD) patients has not been fully established, and little is known about the neuroplastic changes induced by botulinum toxin type A (BoNT-A) treatment.METHODS:Ninety-two CD patients presenting with rotational torticollis and 45 healthy controls from our database were retrospectively screened. After clinical assessment, the 92 patients underwent baseline magnetic resonance imaging (MRI) followed by a single-dose injection of BoNT-A. Four weeks later, 76 out of the 92 patients were re-evaluated with the Tsui scale for dystonia severity, and 33 out of 76 patients completed post-treatment MRI scanning. Data-driven global brain connectivity and regional homogeneity in tandem with seed-based connectivity analyses were used to examine the functional abnormalities in CD and longitudinal circuit alterations that scaled with clinical response to BoNT-A. Multiple regression models were employed for the prediction analysis of treatment efficacy.RESULTS:Cervical dystonia patients exhibited elevated baseline connectivity of the right postcentral gyrus with the left dorsomedial prefrontal cortex and right caudate nucleus, which was associated with their symptom severity. BoNT-A reduced excessive functional connectivity between the sensorimotor cortex and right superior frontal gyrus, which was significantly correlated with changes in Tsui score. Moreover, pre-treatment regional homogeneity of the left middle frontal gyrus was linearly related to varied response to treatment.CONCLUSIONS:Our findings unravel dissociable connectivity of the sensorimotor cortex underlying the pathology of CD and central effects of BoNT-A therapy. Furthermore, baseline regional homogeneity with the left middle frontal gyrus may represent a potential evidence-based marker of patient stratification for BoNT-A therapy in CD.

肌张力障碍是一种以肌肉异常的、不自主收缩引起的异常运动为特征的运动障碍.缓解技巧(alleviating ma-neuvers )是肌张力障碍患者中的常见现象,目前已经被广泛应用于各种类型肌张力障碍的诊断以及与其他疾病的鉴别,但是其发生机制及临床应用正在探索中.本文将对缓解技巧的定义、分类、影响因素、在各类肌张力障碍中的具体表现及其发生机制进行系统综述.

Facial synkinesis can be present in both primary and postparalytic hemifacial spasm (HFS). The present retrospective study aimed to summarize the clinical features of synkinesis and explore an appropriate botulinum toxin A (BoNT-A) injection strategy to manage the synkinesis accompanying HFS. Video recordings of 234 patients with primary and postparalytic HFSs were analyzed. Improvements in the severity of spasm and synkinesis owing to BoNT-A treatment were monitored and compared among 36 primary and 12 postparalytic HFS patients with synkinesis and completed follow-up records. BoNT-A was injected into the voluntary facial region (VFR), the synkinetic facial region (SFR), or both VFR and SFR, and the efficacy of these strategies was evaluated and analyzed. Oral-ocular synkinesis in the primary group (32.8%) and ocular-oral synkinesis in the postparalytic group (81.0%) showed the highest incidence. Patients in both the primary and postparalytic groups exhibited a tremendous alleviation of spasm (97.2% vs. 91.7%, P > 0.05) following BoNT-A treatment. In both groups, coinjection and SFR injection were commonly used and effective in treatment of ocular and oral synkinesis, while VFR was frequently used but ineffective for frontal synkinesis. In addition, the improper muscle selection surrounding the mouth corner resulted in pattern change and treatment failure of oral synkinesis. Synkinesis mostly affected the ocular and oral regions. BoNT-A, via treatment of SFR, is effective against synkinesis accompanying HFS.

Objectives To identify genes that affected protein expression in Chinese hamster ovary (CHO) cells was significant, and we identified the changes in the transcriptome and the functional gene sets that would contribute to increase expression of recombinant protein. Results Here two sub-clones from a methotrexate-treated parental recombinant CHO cell line were selected. The two sub-clones, with different expression levels (qp were 42.8 pg/cell/day and 14.0 pg/cell/day), were analyzed through RNA-seq. More than 600 genes were identified as differently expressed, and we found that the differentially expressed genes were involved in processes such as RNA processing, transcription, protein catabolism, and protein transport. Among these, we cloned genes encoding proteins that were involved in transcription and protein transport to investigate their effect on protein production. Conclusions We found that some genes involved in transcription and protein transport would improve recombinant protein production in CHO cells.

INTRODUCTION:Antibody-based c-mesenchymal-epithelial transition factor (c-Met) inhibition is a promising strategy for hepatocellular carcinoma (HCC) treatment, but the intrinsic agonistic activity of the anti-c-Met antibody limits its application in drug development. Constructing a monovalent one-armed antibody has been reported to be an effective way to create an inhibitory anti-c-Met antibody. MATERIALS AND METHODS:In the present study, a novel monovalent one-armed anti-c-Met antibody was constructed using the knobs-into-holes technology, and its inhibitory effects against HCC and the underlying mechanisms were explored. RESULTS:The one-armed anti-c-Met antibody blocked the hepatocyte growth factor (HGF)/c-Met interaction and the subsequent signal transduction, including phosphorylation of c-Met, Grb2-associated binding protein 1(Gab-1), extracellular regulated protein kinases 1/2(Erk1/2), and Akt, also referred to as protein kinase B (PKB) in HCC cell line HepG2. Furthermore, the autocrine stimulation of HepG2 cell proliferation and HGF-induced HCC cell migration were strongly inhibited by the one-armed anti-c-Met antibody. In addition, the antibody also reduced the HGF-induced proliferation and tube formation of human umbilical vein endothelial cells (HUVECs). Treating HepG2-bearing mice with the one-armed anti-c-Met antibody significantly inhibited the tumor growth in the xenograft nude mouse model. CONCLUSION:The one-armed anti-c-Met antibody derived from the full-length bivalent anti-c-Met antibody might serve as a potential antitumor agent against HCC.