riluzole

P2, N=80, Suspended, UNICANCER | Trial completion date: Oct 2024 --> Mar 2025 | Active, not recruiting --> Suspended | Trial primary completion date: Sep 2024 --> Mar 2025

Moreover, riluzole (RZ)-mediated increased BDNF in vivo in the chemotherapy-exposed mice reversed cognitive decline...Dual-immunofluorescence staining, spatial transcriptomics, and biochemical assessment of RZ-treated irradiated brains demonstrated preservation of synaptic integrity and neuronal plasticity but not neurogenesis and reduced neuroinflammation concurrent with elevated BDNF levels and transcripts compared to vehicle-treated irradiated brains. In summary, oral administration of RZ represents a viable and translationally feasible neuroprotective approach against RICD.

This combination showed greater efficacy than either single agent, and strongly suppressed tumor growth in vivo. Taken together, our studies indicate that riluzole activates cGAS/STING-mediated innate immune responses, which might be exploited to sensitize colorectal tumors to anti-PD-1/PD-L1 therapies. .

P1, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025

P2, N=34, Not yet recruiting, University of California, Irvine

Indeed, riluzole, an N-methyl-D-aspartate (NMDA) glutamate receptor blocker, and edaravone, a reactive oxygen species (ROS) scavenger, are currently the sole two medications approved for ALS treatment. In conclusion, the findings of the present work support the potential of the synthesized indolylacetic derivatives II-IV in ALS treatment. Indeed, in the attempt to realize an association between two active molecules, we assumed that the combination of the indispensable moieties of two small molecules (the opioids containing a 4-piperidinyl ring with the FANS indomethacin) might lead to new medicaments potentially useful for the treatment of amyotrophic lateral sclerosis.

P2, N=51, Active, not recruiting, InFlectis BioScience | Recruiting --> Active, not recruiting

P1, N=288, Recruiting, King's College London

P2/3, N=40, Completed, Charite University, Berlin, Germany | Unknown status --> Completed

In cultured hippocampal neurons, we screened three neuroprotective agents, riluzole (an approved treatment for amyotrophic lateral sclerosis), as well as the ampakines CX546 and CX1739. In conclusion, we established the first middle-aged rat model of cisplatin-induced CRCI, assessing the contribution of medical stress and longitudinal changes in BDNF levels with cognitive function, although future studies are warranted to assess the efficacy of BDNF enhancement in vivo on synaptic plasticity. Collectively, our results indicate that cancer treatment exerts long-lasting changes in BDNF levels, and support BDNF enhancement as a potential preventative approach to target CRCI with therapeutics that are FDA approved and/or in clinical study for other indications.

P2, N=78, Recruiting, University of Utah | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Oct 2024

There was no evidence of myopathy or neuromuscular junction disorder.Setting: Cancer rehabilitation clinicAssessment/ Patient was diagnosed with ALS and started on riluzole... Cancer rehabilitation physicians play a critical role in early recognition and timely diagnosis of disorders like paraneoplastic syndromes and neurodegenerative diseases that can be severely debilitating, difficult to diagnose, and challenging to treat. Patients with a cancer history and concurrent ALS require unique rehabilitation considerations.

P2, N=80, Active, not recruiting, UNICANCER | Recruiting --> Active, not recruiting | N=210 --> 80 | Trial completion date: Apr 2024 --> Oct 2024 | Trial primary completion date: Sep 2023 --> Sep 2024

In motor neurons of trametinib+riluzole administrated SOD1-G93A mice, the level of cathepsin D and the co-localization of LC3 and LAMP1 increased, while abnormal p62 accumulation was significantly reduced, indicating improvement of autophagic flux. Altogether, these data suggest that low dose trametinib+riluzole combination therapy is pharmacologically superior to monotherapy in the ALS mouse model and could serve as a promising clinical combination for the improvement of current neuroprotective treatment strategies of ALS.

H-MRS demonstrated altered membrane turnover over 96-weeks in the placebo group. It also distinguished changes in neuro-metabolites related to gliosis and glutaminergic transmission, due to fluoxetine and riluzole, respectively. Data show tNAA is a potential marker for upper limb function.

Our GBM-targeted network analysis allowed us to effectively identify potential candidates for drug repurposing or repositioning. Further validation will be conducted by using other different types of biomedical and clinical data and biological experiments. The findings could lead to less invasive treatments for glioblastoma while significantly reducing research costs by shortening the drug development timeline. Furthermore, this workflow can be extended to other disease areas.

We previously reported that the acquisition of tamoxifen resistance in a cellular model of invasive lobular breast cancer is accompanied by the upregulation of GRM mRNA expression and growth inhibition by riluzole. Single-agent riluzole significantly inhibited HCI-013EI patient-derived xenograft growth in vivo, and the combination of riluzole plus fulvestrant significantly reduced proliferation in ex vivo primary breast tumor explant cultures. Riluzole may offer therapeutic benefits in diverse ER+ breast cancers, including lobular breast cancer.

P1, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2023 --> Sep 2024

Other pharmacological strategies that downregulate glutamatergic signalling include riluzole, memantine and anaesthetic agents. Similarly, the significant survival benefit in glioblastoma attributable to alternating electrical fields (Tumour Treating Fields) may be a result of disruption to neurogliomal signalling. Further studies exploring excitatory neurotransmission and glutamatergic signalling and their role in glioma origin, growth and propagation are therefore warranted.

Case 1: 73-year-old woman, January 2014 retroperitoneal leiomyosarcoma of the ureter - R0 en bloc resection with partial resection of the ureter and left hemicolectomy - Transcriptome-guided adjuvant treatment: Sorafenib and Riluzole due to GRM1 gene overexpression - Scapular recurrence with bone infiltration in Sept...Treatment with Tazemetostat in December 2022...- Neoadjuvant chemotherapy and radiotherapy treatment, R0 wide surgery with adequate preservation of functionality and IORT - Early chest wall dermal/subcutaneous recurrence (resected) after initiation of immunotherapy – Nivolumab – due to a favorable profile for immunotherapy in tumor transcriptome - Genome of recurrence: BRAF V600E mutation. Treatment with Dabrafenib + Trametinib... STS are tumors with complex surgical and oncological management and a poor response to conventional chemotherapy protocols. Given its heterogeneity, precision oncology through molecular profiling with next-generation massive sequencing (panels for tumor genome and transcriptome) allows the development of personalized therapeutic strategies in patients with STS, and opens up the possibilities for targeted treatments for molecular alterations, immunotherapy and the development of new agents.

P1, N=13, Active, not recruiting, Ning Jin | Recruiting --> Active, not recruiting

Combination therapy with riluzole and sorafenib was safe and tolerable in patients with advanced solid tumors. The partial response in a patient with a RAF1 fusion suggests that further exploration in a genomically selected cohort may be warranted.

In this study, we utilized a fully immuno-competent, transgenic mouse model, TGS, in which the spontaneous development of metastatic melanoma is driven by the ectopic expression of a normal neuronal receptor, metabotropic glutamate receptor 1 (mGluR1), as a model to assess longitudinal treatment response (up to 8 months) with an inhibitor of glutamatergic signaling, troriluzole, a prodrug of riluzole, plus an antibody against programmed cell death protein-1 (PD-1), an immune-checkpoint inhibitor. Our results reveal a sex-biased treatment response that led to an improved survival in troriluzole and/or anti-PD-1 treated male mice that correlated with differential CD8 T-cells and CD11b myeloid cell populations in the tumor-stromal interface, supporting the notion that this model is a responsive and tractable system for evaluating therapeutic regimens for melanoma in an immuno-competent setting.

Importantly, RZ mitigated chemotherapy-induced loss of newly born, immature neurons, dentate neurogenesis, and neuroinflammation. In conclusion, this data provides pre-clinical evidence for a translationally feasible approach to enhance the neuroprotective effects of RZ treatment to prevent CRCI.

The H,K-ATPase inhibitor omeprazole reduced carbachol- and riluzole-induced anion transport responses. KCNE1 mRNA and TREK-1, TREK-2, TASK-2, and KCNQ1 protein expression were also shown. This study shows that the Capan-1 model recapitulates key physiological aspects of a bicarbonate-secreting epithelium and constitutes a valuable model for functional studies on human pancreatic duct epithelium.

P1, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2022 --> Sep 2023

Finally, riluzole inhibits pancreatic cancer growth in KPC (Pdx1-Cre, LSL-Trp53, and LSL-Kras) mice. In conclusion, riluzole can inhibit pancreatic cancer growth by regulating glucose and glutamine metabolisms and can be used to treat pancreatic cancer.

P1, N=36, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2022 --> Aug 2022 | Trial primary completion date: May 2022 --> Aug 2022

P1, N=36, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2022 --> May 2022 | Trial primary completion date: Jan 2022 --> May 2022

Subsequently, we demonstrated that Riluzole enhanced activity of the Bax promoter in a luciferase reporter assay and enhanced YAP/p73 binding on endogenous Bax promoter in a ChIP assay. Our data supports a novel mechanism in which Riluzole activates c-Abl kinase to regulate pro-apoptotic activity of YAP in osteosarcoma.

Incidence rates of ALS are increasing over time, but there are no effective treatments at present due to limitations on approved therapies (riluzole and edaravone)...Furthermore, it reduced oxidative stress-induced TDP-43 aggregates and lowered the levels of autophagy-related proteins, including p62, light chain 3b, and ATG8, in TDP-43-expressing cells. Our results suggest that this combined treatment could be helpful for autophagy regulation in other neurodegenerative diseases.

P1, N=36, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2021 --> Nov 2021 | Trial primary completion date: Aug 2021 --> Nov 2021

P1, N=36, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Apr 2018 --> Aug 2021

Western blot results demonstrated that 4a suppressed Bcl-2 protein expression but increased the level of Bax in HeLa cells, and elevated the Bax/Bcl-2 expression ratio. These new findings suggest that 4a exhibited beneficially anti-cervical cancer effect on HeLa cells by inducing HeLa cell apoptosis.

P1, N=36, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Mar 2020 --> Jun 2020

P1, N=36, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Dec 2019 --> Mar 2020

The neuropathology in FUS-tg mice is sensitive to standard ALS treatments and Neuro-Cells infusion. The latter improves motor outcomes in two ALS models possibly by suppressing microglial activation.