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- | Xiflam (tonabersat) / InflammX
Preclinical, Journal: Integrating and optimizing tonabersat in standard glioblastoma therapy: A preclinical study. (Pubmed Central) - Mar 19, 2024
The study suggests tonabersat's potential to reduce tumor invasiveness, providing a new avenue for GB treatment. In conclusion, this preclinical investigation highlights tonabersat's potential as an effective adjuvant treatment for GB, and its established safety profile from clinical trials in migraine treatment presents a promising foundation for further exploration.
- | Xiflam (tonabersat) / InflammX
Preclinical, Journal: Tonabersat Significantly Reduces Disease Progression in an Experimental Mouse Model of Multiple Sclerosis. (Pubmed Central) - Dec 27, 2023
MOG EAE mice showed clinical signs of MS, but MOG EAE mice treated with tonabersat retained behavior closer to normal. These data suggest that clinical trial phase IIb-ready tonabersat may merit further investigation as a promising candidate for MS treatment.
- | Xiflam (tonabersat) / InflammX
Enrollment open: AN: Evaluation of Tonabersat for DME (clinicaltrials.gov) - Jun 18, 2023
P2, N=128, Recruiting, Sponsor: Jaeb Center for Health Research
These data suggest that clinical trial phase IIb-ready tonabersat may merit further investigation as a promising candidate for MS treatment. Not yet recruiting --> Recruiting
- | Xiflam (tonabersat) / InflammX
Preclinical, Journal: Orally Delivered Connexin43 Hemichannel Blocker, Tonabersat, Inhibits Vascular Breakdown and Inflammasome Activation in a Mouse Model of Diabetic Retinopathy. (Pubmed Central) - Mar 2, 2023
However, the tonabersat treatment in the inflammatory NOD mice significantly reduced macrovascular abnormalities, hyperreflective foci, sub-retinal fluid accumulation, vascular leak, inflammation, and inflammasome activation. These findings suggest that tonabersat may be a safe and effective treatment for DR.
- | Xiflam (tonabersat) / InflammX
New P2 trial: AN: A Phase 2 Evaluation of Tonabersat for DME (clinicaltrials.gov) - Feb 14, 2023
P2, N=128, Not yet recruiting, Sponsor: Jaeb Center for Health Research
- | Xiflam (tonabersat) / InflammX
Journal: Blocking connexin-43 hemichannel-mediated ATP release reduces communication within and between tubular epithelial cells and medullary fibroblasts in a model of diabetic nephropathy. (Pubmed Central) - Nov 19, 2022
Tonabersat-sensitive hemichannel-mediated ATP release enhances TGFβ1-driven heterotypic cell-cell interaction and favours myofibroblast activation. The data supports the potential benefit of Cx43 inhibition in reducing tubulointerstitial fibrosis in late-stage diabetic nephropathy.
- | Xiflam (tonabersat) / InflammX
Journal: Cx43 hemichannels contribute to astrocyte-mediated toxicity in sporadic and familial ALS. (Pubmed Central) - Apr 21, 2022
SignificanceOur results demonstrate that connexin 43 hemichannels are the conduits for amyotrophic lateral sclerosis (ALS) astrocyte-mediated motor neuron toxicity and disease spread, acting as a common mechanism that can target both familial ALS and sporadic ALS populations. Furthermore, our present work provides proof of principle that tonabersat, as a drug already studied in clinical trials for other indications, could serve as a potential ALS therapeutic.
- | Xiflam (tonabersat) / InflammX
Journal: Blocking connexin43 hemichannels prevents TGF-β2 upregulation and epithelial-mesenchymal transition in retinal pigment epithelial cells. (Pubmed Central) - Apr 5, 2022
All of these changes were significantly reduced with tonabersat treatment, which also prevented HG + Cyt-induced TGF-?2 release. In conclusion, Cx43 hemichannel block with tonabersat attenuated both TGF-?2 release and RPE EMT under disease-mimicking conditions, offering the potential to ameliorate the progression of EMT-associated retinal diseases.
- | tonabersat (USL260) / Sawai Pharma
Preclinical, Journal: Tonabersat Inhibits Connexin43 Hemichannel Opening and Inflammasome Activation in an In Vitro Retinal Epithelial Cell Model of Diabetic Retinopathy. (Pubmed Central) - Sep 15, 2021
It also prevented the release of proinflammatory cytokines IL-1β, VEGF, and IL-6. Tonabersat therefore has the potential to reduce inflammasome-mediated inflammation in diabetic retinopathy.
- | tonabersat (USL260) / Sawai Pharma
Journal: Connexin43 hemichannel block inhibits NLRP3 inflammasome activation in a human retinal explant model of diabetic retinopathy. (Pubmed Central) - Apr 27, 2021
Furthermore, we showed that by blocking connexin43 hemichannels with the hemichannel modulator, tonabersat we were able to prevent NLRP3 inflammasome complex aggregation, Müller cell activation, as well as release of pro-inflammatory cytokines and VEGF. This further supports the possible use of connexin43 hemichannel blockers as potential new therapies for DR.
- | tonabersat (USL260) / Sawai Pharma
Journal: Differential Action of Connexin Hemichannel and Pannexin Channel Therapeutics for Potential Treatment of Retinal Diseases. (Pubmed Central) - Apr 20, 2021
The analysis showed that treatment with tonabersat alone was better than probenecid alone at restoring retinal function in the light-damaged retina model. The results assist in the interpretation of the differential action of connexin hemichannel and pannexin channel therapeutics for potential treatment of retinal diseases.
- | tonabersat (USL260) / Sawai Pharma
Preclinical, Journal: Connexin Hemichannel Block Using Orally Delivered Tonabersat Improves Outcomes in Animal Models of Retinal Disease. (Pubmed Central) - Feb 5, 2021
Inflammation was also reduced and retinal electrical function restored. Tonabersat regulates assembly of the inflammasome (NLRP3) through Connexin43 hemichannel block, with the potential to reduce inflammation, restore vascular integrity and improve anatomical along with some functional outcomes in retinal disease.
- || tonabersat (USL260) / Sawai Pharma
Review, Journal: Connexin therapeutics: blocking connexin hemichannel pores is distinct from blocking pannexin channels or gap junctions. (Pubmed Central) - Sep 30, 2020
Blocking the different channel types has distinct physiological and pathological implications and this review describes current knowledge of connexin and pannexin protein channels, their function as channels and possible mechanisms of the channel block effect for the latest therapeutic compounds. We summarize the evidence implicating pannexins and connexins in disease, considering their homeostatic versus pathological roles, their contribution to excesive ATP release linked to disease onset and progression.
- | tonabersat (USL260) / Sawai Pharma
Journal: Adjuvant therapeutic potential of tonabersat in the standard treatment of glioblastoma: A preclinical F98 glioblastoma rat model study. (Pubmed Central) - Mar 22, 2020
We summarize the evidence implicating pannexins and connexins in disease, considering their homeostatic versus pathological roles, their contribution to excesive ATP release linked to disease onset and progression. Our results demonstrate a therapeutic potential of tonabersat for the treatment of GB when used in combination with radiotherapy and temozolomide chemotherapy.
- | tonabersat (USL260) / Sawai Pharma
Journal: Targeting connexin hemichannels to control the inflammasome: the correlation between connexin43 and NLRP3 expression in chronic eye disease. (Pubmed Central) - Mar 8, 2020
Expert Opinion: In over 25 different animal models of disease, connexin hemichannel regulation has shown therapeutic benefit, and at least one oral connexin hemichannel blocker, tonabersat (Xiflam), is Phase II ready with safety evidence in over 1000 patients. Regulating the connexin hemichannel provides a means to move quickly into clinical trials designed to ameliorate the progression of devastating chronic diseases of the eye, but also elsewhere in the body.