botulinum toxin E (AGN-151586) / AbbVie - LARVOL DELTA

Regulation of Botulinum neurotoxin half‑life through the ubiquitin‑proteasome system. (PubMed, Mol Med Rep) - "Ubiquitination was observed in the light chains of BoNT/A1 (K335 and K417), BoNT/A2 (K335) and BoNT/E (K62 and K288), which were identified as key ubiquitination sites. The substitution of these lysine residues to arginine inhibited ubiquitination, improving protein stability and extending the half‑life of BoNT. These findings offer a potential strategy to enhance the therapeutic efficacy of BoNT by prolonging its stability, paving the way for future advancements in BoNT‑based treatments."

Journal • Targeted Protein Degradation

A Study to Assess the Adverse Events of Intramuscular Injections of AGN-151586 and OnabotulinumtoxinA in Adult Participants for the Change of Glabellar Lines (GL) (clinicaltrials.gov) - P1 | N=132 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Adverse events • Enrollment closed

Single Tri-Epitopic Antibodies (TeAbs) to Botulinum Neurotoxin Serotypes B, E, and F Recapitulate the Full Potency of a Combination of Three Monoclonal Antibodies in Toxin Neutralization. (PubMed, Toxins (Basel)) - "Each TeAb (TeAb-B for BoNT/B, TeAb-E for BoNT/E, and TeAb-F for BoNT/F) binding was measured using fluorescence-activated cell sorting and flow fluorimetry, and the potency was tested in the MNA...We now have four examples of a single TeAb recapitulating the affinity and in vivo potency of a three-mAb antitoxin. The tri-epitopic strategy could be applied to streamline the production and bioanalytics of antibody drugs where three-mAb binding is required for activity."

Journal

Preclinical Evaluation of Botulinum Toxin Type E (TrenibotulinumtoxinE) Using the Mouse Digit Abduction Score (DAS) Assay. (PubMed, Toxins (Basel)) - "A comparative analysis was also performed between trenibotE and an equi-efficacious dose of the botulinum neurotoxin serotype A (BoNT/A) onabotulinumtoxinA (onabotA). A comparison of onabotA and trenibotE in this assay at approximate equi-efficacious doses showed trenibotE to have a faster onset of effect (trenibotE yielded a significantly greater effect as early as 6 h post-injection), shorter time to peak effect (24-27 h vs. 2 days), and an overall shorter duration of response (3 days vs. 14 days). The unique temporal characteristics of trenibotE and pharmacological differentiation from onabotA observed in this preclinical assay support the clinical development of this molecule."

Journal • Preclinical

Widespread occurrence of botulinum and tetanus neurotoxin genes in ancient DNA. (PubMed, Toxicon) - "Our work reveals that clostridial neurotoxin genes occur frequently in aDNA samples, including human and animal-associated toxin variants. We conclude that the frequent association of these genes with aDNA likely reflects a strong ecological association of pathogenic clostridia with decaying human and animal remains and possible post-mortem colonization of these samples."

Journal • Infectious Disease • Tetanus

Can Botulinum Toxin Type E Serve as a Novel Therapeutic Target for Managing Chronic Orofacial Pain? (PubMed, Toxins (Basel)) - "In comparison, intraperitoneally administered gabapentin (30, 100 mg/kg) demonstrated significant mechanical anti-allodynic effects but exhibited lower analgesic efficacy than that of BoNT-E. These findings highlight the potential of BoNT-E as a therapeutic agent for chronic pain management."

Journal • Immunology • Neuralgia • Pain • FOS

A Study to Evaluate AGN-151586 Intramuscular Injections in Adult Participants for Treatment of Glabellar Lines (clinicaltrials.gov) - P3 | N=161 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed

Trial completion

A Study to Assess the Adverse Events of Intramuscular Injections of AGN-151586 and OnabotulinumtoxinA in Adult Participants for the Change of Glabellar Lines (GL) (clinicaltrials.gov) - P1 | N=126 | Not yet recruiting | Sponsor: AbbVie

Adverse events • New P1 trial

A Study to Assess the Adverse Events of Intramuscular Injections of AGN-151586 and OnabotulinumtoxinA in Adult Participants for the Change of Glabellar Lines (GL) (clinicaltrials.gov) - P1 | N=126 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Adverse events • Enrollment open

Probing the properties of PTEN specific botulinum toxin type E mutants. (PubMed, J Neural Transm (Vienna)) - "The fusion protein LCE-16x-BoNT/Di could be produced in sufficient yields. Activity tests using rat cerebellar granule neurons showed BoNT/E-like activity for LC/E-wt-BoNT/Di, but no PTEN-directed activity for LC/E-16x-BoNT/Di."

Journal • PTEN

Inter-Domain interactions Slow BoNT/A's onset of action. (PubMed, J Struct Biol) - "In good agreement with previous work, CD showed a gradual and small loss of helicity as the pH decreased below pH 5.5, stabilising at pH 4.5. Combined with the relative scarcity of structural changes observed by MD in the switch region required for activity, these results may explain the slower onset of action for BoNT/A compared to BoNT/E."

Journal

A Study to Evaluate AGN-151586 Intramuscular Injections in Adult Participants for Treatment of Glabellar Lines (clinicaltrials.gov) - P3 | N=161 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Enrollment closed

Development of a loop-mediated isothermal amplification method for the rapid detection of Clostridium botulinum serotypes E and F. (PubMed, Mol Biol Rep) - "For future directions, applications of the established method, especially with the degenerate primers, could be used as an alternative assay for the rapid and sensitive detection of C. botulinum."

Journal

Comparative Phylogenetic Analysis and Protein Prediction Reveal the Taxonomy and Diverse Distribution of Virulence Factors in Foodborne Clostridium Strains. (PubMed, Evol Bioinform Online) - "The BoNTs have highly similar structures, but BoNT/A/B and BoNT/E/F have significantly different conformations...According to the genotype of protein-coding virulence genes, the evolution of Clostridium showed a clustering trend. The genetic stability, functional and structural characteristics of foodborne Clostridium virulence proteins reveal the taxonomy and diverse distribution of virulence factors."

Journal

Spatial distribution and factors associated with HIV testing among adolescent girls and young women in Sierra Leone. (PubMed, BMC Infect Dis) - "Despite some positive trends, HIV testing rates among adolescent girls and young women in Sierra Leone remain moderate. Spatial autocorrelation analysis consistently revealed hotspots and cold spots for HIV testing, with Kailahun, Kambia, Tonkolil, some parts of the Western rural area, and Bonthe districts remaining persistent hotspots. Age, education, internet use, sexual history, parity, and healthcare access are significant factors influencing testing behaviour. To improve testing rates, the government and policymakers should prioritize educational campaigns, expand internet access, integrate HIV testing into routine healthcare, and address stigma associated with HIV."

Journal • Human Immunodeficiency Virus • Infectious Disease

Botulinum toxine and hyaluronic acid - when, where and how to inject both - an advanced guide (EADV 2024) - No abstract available

Metastases

Botulinum toxine and laser/light therapy - how to get the best results from a combination therapy (EADV 2024) - No abstract available

Combination therapy

Novel platform for engineering stable and effective vaccines against botulinum neurotoxins A, B and E. (PubMed, Front Immunol) - "To address this urgent need, we have developed an innovative vaccine platform by fusing the neuronal binding domain of BoNT/E (Hc/E) with core-streptavidin (CS), resulting in a stable CS-Hc/E vaccine...Our findings highlight EBA's potential as a stable and effective broad-spectrum vaccine against BoNT. Moreover, our technology offers a versatile platform for developing multivalent, stable vaccines targeting various biological threats by substituting the BoNT domain(s) with neutralizing epitopes from other life-threatening pathogens, thereby enhancing public health preparedness and biodefense strategies."

Journal

Preoperative Progressive Pneumoperitoneum and Botulinum Toxin A in a High-Risk Patient With Loss of Domain Inguinoscrotal Hernia. (PubMed, Cureus) - "The technique proved safe, feasible, and effective, contributing to atraumatic adhesiolysis, reduced operative time, and avoidance of more invasive surgical methods. A Shouldice pure tissue repair was performed, successfully avoiding the need for prosthetic materials."

Journal • Gastroenterology

Real-time PCR assays that detect genes for botulinum neurotoxin A-G subtypes. (PubMed, Front Microbiol) - "Seventeen specific assays (two for each of the bont/C, bont/D, bont/E, and bont/G subtypes and three for each of the bont/A, bont/B, and bont/F subtypes) were designed and evaluated for their ability to detect bont genes encoding multiple subtypes from all seven serotypes. These assays could provide an additional tool for the detection of botulinum neurotoxins in clinical, environmental and food samples that can complement other existing methods used in clinical diagnostics, regulatory, public health, and research laboratories."

Journal

Intramuscular Botulinum Neurotoxin Serotypes E and A Elicit Distinct Effects on SNAP25 Protein Fragments, Muscular Histology, Spread and Neuronal Transport: An Integrated Histology-Based Study in the Rat. (PubMed, Toxins (Basel)) - "Interestingly, SNAP25C-ter completely disappeared for both toxins during the peak of efficacy, suggesting that the persistence of toxin effects is driven by the persistence of proteases in tissues. These data unveil some new molecular mechanisms of action of the short-acting BoNT/E and long-acting BoNT/A, and reinforce their overall safety profiles."

Journal • Preclinical

Do lower doses of botulinum toxin offer a longer duration of effect and superior efficacy in patients with cervical dystonia? (IAPRD 2024) - No abstract available.

Study of AGN-151586 in Japanese Participants With Moderate to Severe Glabellar Lines (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed

Trial completion

A Study to Evaluate AGN-151586 Intramuscular Injections in Adult Participants for Treatment of Glabellar Lines (clinicaltrials.gov) - P3 | N=160 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Evaluate AGN-151586 Intramuscular Injections in Adult Participants for Treatment of Glabellar Lines (clinicaltrials.gov) - P3 | N=160 | Not yet recruiting | Sponsor: AbbVie

New P3 trial