P2, N=24, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Nov 2024 --> Nov 2025

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.

P1, N=24, Completed, AbbVie | Active, not recruiting --> Completed

P3, N=160, Recruiting, AbbVie | Not yet recruiting --> Recruiting

Additionally, our findings suggest that Bcl-2 and Bax proteins may be involved in the molecular mechanism triggered by IL-3. Our investigation into IL-3's ability to protect neuronal cells from glutamate-induced damage offers a promising therapeutic avenue with potential clinical implications for several neurological diseases characterized by glutamate neurotoxicity.

P3, N=160, Not yet recruiting, AbbVie

P1, N=24, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting

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

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

P1, N=24, Recruiting, AbbVie | Not yet recruiting --> Recruiting | Phase classification: P1/2 --> P1

P2, N=24, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2023 --> Nov 2024

P1/2, N=24, Not yet recruiting, AbbVie

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

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.

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.

We developed a multidrug-resistant colorectal cancer cell line, HCT-116, after treatment with cisplatin and 5-fluorouracil. Additionally, GDH1 knockdown on both HCT-116 and HCT-116 corresponded to a decreased expression of γH2AX, catalase, SOD1 and Gpx-1, and an eventual increase in apoptosis markers. In conclusion, inhibition of GDH1 increased ROS production, decreased cell proliferation and increased cell death.

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.

OximUNO comprises a star-shaped polyglutamate (St-PGA) decorated with the CD206-targeting peptide mUNO that carries the chemotherapeutic drug doxorubicin (DOX)...Importantly, our studies also represent a novel design of a peptide-targeted St-PGA as a targeted therapeutic nanoconjugate. A peptide-targeted nanoformulation of DOX exclusively eliminates mannose receptor+ TAMs in breast cancer models, generating response without off-target effects (a drawback of many TAM-depleting agents under clinical study).

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.

Moreover, GDH1, RSK2, and CREB phosphorylation positively correlate with EGFR mutation and activation in lung cancer patient tumors. Our findings reveal a crosstalk between kinase, metabolic, and transcription machinery in metastasis and offer an alternative combinatorial therapeutic strategy to target metastatic cancers with activated EGFRs that are often EGFR therapy resistant.

This effect was not observed in MCF7 breast cancer cells that do not have a KRas mutation or in BJ-hTERT human fibroblasts which have no oncogenic mutation. These data reveal a synthetic lethality between inhibition of glutamate oxaloacetate transaminase and ACLY inhibition that is specific for KRas-driven cancer cells and the apparent metabolic reprogramming induced by activating mutations to KRas.

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

Endogenous metabolism changes occur due to drug action and might be indicative of antitumor therapeutic effect. These findings will provide new clues for identifying the antitumor mechanism of these two treatments from the perspective of metabolism.

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.

Biguanides, by compromising mitochondria and reducing systemic glucose availability, and the glutaminase inhibitor telaglenastat (CB-839), inhibiting glutamate production and reducing carbon intermediates essential for TCA cycle progression, have provided the most interesting results and entered different clinical trials enrolling also LKB1-null NSCLC patients...In conclusion, the absence of the target did not block the development of treatments able to hit LKB1-mutated NSCLCs acting on several fronts. This will give patients a concrete chance to finally benefit from an effective therapy.

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.