cyclosporin A microemulsion

P4, N=648, Completed, University Hospital, Clermont-Ferrand | Unknown status --> Completed

Cyclosporin A, a calcineurin inhibitor that decreases T cell activation, has proven effective for induction of remission, but its long-term side effects limit its appeal for maintenance...Sirolimus and everolimus have interesting effects on regulatory T cell populations and may become viable options in the future. Mycophenolate mofetil is not effective for induction but is a valid alternative for patients who are intolerant to azathioprine. B cell-depleting drugs, such as rituximab and belimumab, have been successfully used in refractory cases and are useful in both the short and long term. Other promising treatments include anti-tumor necrosis factors, Janus kinases inhibitors, and chimeric antigen receptor T cell therapy. This growing armamentarium allows us to imagine a more tailored approach to the treatment of autoimmune hepatitis in the near future.

P=N/A, N=200, Recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

STIM1 can promote autophagy and accelerate cervical cancer progression by increasing TFEB nuclear translocation of cervical cancer cells.

P3, N=102, Recruiting, Bristol-Myers Squibb | Trial completion date: Jan 2028 --> Dec 2031

P3, N=150, Not yet recruiting, University of California, San Francisco

P2, N=54, Active, not recruiting, Institute of Hematology & Blood Diseases Hospital, China | Recruiting --> Active, not recruiting

Cyclosporine A combined with artificial tears is effective in treating dry eye, yielding enhanced outcomes by improving SIT and TBUT levels, reducing CFS scores, and ameliorating vision-related quality of life.

Moreover, CyA-loaded ILs (0.5%, w/w) significantly relieved the symptoms of psoriasis in an imiquimod (IMQ)-induced mouse model, and the levels of inflammatory factors, including tumor necrosis factor α, interleukin 22 and interleukin 17, in the affected area were reduced by 71.7%, 75.6%, and 89.3%, respectively. After 7 days of consecutive application, [Ch][So] did not cause significant irritation. In conclusion, ILs demonstrate promising potential for the dermal delivery of CyA for the treatment of psoriasis.

P2, N=40, Active, not recruiting, Boston Children's Hospital | Trial primary completion date: Apr 2024 --> Dec 2024

To explore the efficacy and the mechanism of the umbilical cord-derived cells combined with cyclosporine A (CsA) in treating aplastic anemia (AA) in mice...Treatment with CsA + UC-MSC upregulated superoxide dismutase activity compared with CsA + UCB-Treg treatment. Adding UC-MSC or UCB-Treg to CsA markedly enhanced the reconstruction of hematopoiesis in AA mice, with UC-MSC eliciting greater efficiency than UCB-Treg. Accordingly, the addition of these cells could further improve immune abnormalities.

P=N/A, N=40, Completed, University of Waterloo | Recruiting --> Completed

P4, N=823, Completed, First Affiliated Hospital of Guangxi Medical University | Recruiting --> Completed | Trial completion date: May 2023 --> Oct 2023

P2, N=40, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P2, N=54, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Oct 2025 --> Oct 2032 | Trial primary completion date: Oct 2024 --> Oct 2031

Additionally, neither body weight nor artery tissue were affected due to PINK1 and Parkin suppression Cyclosporin A in Mp-LAMPs-treated mice. These findings indicated that PINK1/Parkin-mediated mitophagy inhibition may be a therapeutic target for MP-induced KD.

P4, N=54, Not yet recruiting, Peking Union Medical College Hospital

CsA treatment might be helpful for certain patients with ABCA3 deficiency, however, currently strong clinical supporting evidence is lacking. Appropriate trials are necessary to overcome this unmet need.

P=N/A, N=315, Completed, Erasmus Medical Center

Our data revealed the pathological role of the mtDNA-IRF1-ZBP1 axis in OA chondrocytes, suggesting that inhibition of this axis could be a viable therapeutic approach for OA.

Clinical presentation of the local paediatric uveitis differs from previously described features in Caucasian and other populations. According to our experience as a tertiary eye centre, Behçet's disease, tubulointerstitial nephritis and uveitis and HLA-B27 associated uveitis were more often encountered than Juvenile Idiopathic Arthritis associated uveitis. Our report evaluated the efficacy of immunomodulatory therapy and biologics in controlling uveitis and reducing ocular complications.

Interestingly, the immune-staining for tumor necrosis factor (TNF-α) was tested negative and mild positive in renal tissue of rats given Lir and/or Res while being treated with Cs A which indicated their anti-inflammatory effect that reduced the renal damage. The findings of this investigation revealed the ameliorative anti-inflammatory in addition to the antioxidant role of both liraglutide and resveratrol against the kidney damage caused due to CsA administration.

P2, N=150, Active, not recruiting, Fred Hutchinson Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: Oct 2026 --> May 2025 | Trial primary completion date: Oct 2026 --> May 2025

Cyclosporin A (CsA) induces DNA double-strand breaks in LIG4 syndrome fibroblasts, specifically upon transit through S-phase...We explore examples of how CYPA inhibition may be exploited to selectively kill cancers sharing characteristic genomic instability profiles, including MYCN-driven Neuroblastoma, Multiple Myeloma and Chronic Myelogenous Leukaemia. These findings propose a repurposing strategy for Cyclophilin inhibitors.

ICA inhibits the activation of excessive autophagy and thus improves mitochondrial dysfunction by blocking the mPTP opening.

Erdafitinib, a tyrosine kinase inhibitor of fibroblast growth factor receptors 1 to 4, is administered for the treatment of locally advanced, unresectable or metastatic urothelial carcinoma but however is fraught with several systemic and ocular side effects.Concurrent anterior and posterior segment ocular involvement could be encountered in patients undergoing erdafitinib therapy.Maintaining a high level of suspicion and closely monitoring for potential ocular complications through collaborative efforts is essential for all patients undergoing erdafitinib therapy.

We further demonstrate that an FDA-approved drug, cyclosporin A (CsA), impairs the interaction of NRF2 with PPIA, inducing NRF2 ubiquitination and degradation...CsA and a glutaminase inhibitor combination therapy significantly retard tumor progression in NSCLC patient-derived xenograft (PDX) models with NRF2 hyperactivation. Our study demonstrates that targeting NRF2 protein stability is an actionable therapeutic approach to treat NRF2-hyperactivated NSCLC.

P2, N=140, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

P=N/A, N=76, Active, not recruiting, University of British Columbia | Trial completion date: Dec 2023 --> Dec 2024

P2, N=204, Not yet recruiting, University Hospital Heidelberg | Trial completion date: Mar 2027 --> Oct 2027 | Initiation date: Feb 2024 --> Oct 2024 | Trial primary completion date: Mar 2026 --> Oct 2026

P2, N=140, Recruiting, M.D. Anderson Cancer Center | N=100 --> 140

Consequently, relying solely on CsA is insufficient to achieve optimal therapeutic outcomes. It is necessary to simultaneously target both the calcineurin-NFAT pathway and the mTORC1 pathway to maximize therapeutic efficacy.

The spontaneous reassembly of GFP-MxA condensates in oral epithelial cells, even under continuous saliva-like hypotonicity, was slowed by the protein-phosphatase-inhibitor cyclosporin A (CsA) and by the K-channel-blocker tetraethylammonium chloride (TEA); this is suggestive of the involvement of the volume-sensitive WNK kinase-protein phosphatase (PTP)-K-Cl cotransporter (KCC) pathway in the regulated volume decrease (RVD) during condensate reassembly in oral cells. The present study identifies a novel subcellular consequence of hypotonic stress in oral epithelial cells, in terms of the rapid and dynamic changes in the structure of one class of phase-separated biomolecular condensates in the cytoplasm-the antiviral MxA condensates. More generally, the data raise the possibility that hypotonicity-driven stresses likely affect other intracellular functions involving liquid-liquid phase separation (LLPS) in cells of the oral mucosa.

P=N/A, N=158, Not yet recruiting, Siriraj Hospital

P2, N=54, Recruiting, Fred Hutchinson Cancer Center | Not yet recruiting --> Recruiting

P1, N=40, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Mar 2025

P1, N=40, Active, not recruiting, National Cancer Institute (NCI)

Infection was identified in 8 of 9 patients: adenovirus, HHV6, EBV, and Streptococcus Group A. Only 2 patients received HLH-2004 therapy (dexamethasone, etoposide, cyclosporin-A) and the others received dexamethasone and/or intravenous gamma globulins (IVIG), with rapid resolution of fever (median 2 days). Early intervention with corticosteroids and/or IVIG may prevent deterioration, spare them from chemotherapy and provide time for more elaborate testing to identify true HLH. Unfortunately, mortality remains a significant risk for these children.

P1, N=120, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2023 --> Dec 2025

Key compounds identified through these networks included Zinc, Mebendazole, Levomenol, Gefitinib, Niclosamide, and Imatinib...Laboratory Studies: This study determined that Mebendazole, Gefitinib, Topotecan and to some extent Carfilzomib showed conventional drug-response curves, with IC50 values near or below that of Remdesivir with excellent confidence all above R2>0.91, and no cytotoxicity at the IC50 concentration in Calu-3 cells. Cyclosporine A showed antiviral activity, but also unconventional drug-response curves and low R2 which are explained by the non-dose dependent toxicity of the compound...Our preliminary findings underscore the therapeutic promise of several compounds, notably Mebendazole, in both in vitro and in vivo settings against SARS-CoV-2. Several of the drugs explored, especially Mebendazole, are off-label medication; their cost-effectiveness position them as economical therapies against SARS-CoV-2.

P2, N=135, Active, not recruiting, Fred Hutchinson Cancer Center | Trial completion date: Dec 2025 --> Dec 2024

P=N/A, N=40, Recruiting, University of Waterloo | Trial completion date: Aug 2023 --> Apr 2024 | Trial primary completion date: Aug 2023 --> Apr 2024