riluzole / Generic mfg. - LARVOL DELTA

Treatment of primary adult-onset neurodegenerative cerebellar ataxias. (PubMed, Neurotherapeutics) - "Pharmacological approaches, including omaveloxolone for Friedreich's ataxia and off-label agents such as riluzole, 4-aminopyridine, and varenicline, demonstrate subtype-specific benefits. In parallel, molecular and gene-based therapies-including antisense oligonucleotides, viral vector delivery systems, and CRISPR-based strategies-are advancing into preclinical and early-phase clinical studies. This evolving therapeutic landscape underscores a shift toward personalized, multimodal care for cerebellar ataxias and highlights the need for continued translational efforts to bridge mechanistic insights with clinical impact."

Journal • Review • Ataxia • CNS Disorders • Friedreich ataxia • Movement Disorders

Trimorphism in riluzole salicylate: screening, crystal structures and solution thermodynamics. (PubMed, Pharm Res) - "Polymorphism significantly affects the pharmaceutical properties of riluzole salicylate. Selective preparation of polymorphs enables tuning of solubility and dissolution, linking crystal structure and thermodynamics to drug delivery optimization. Slower release kinetics of Form 1 compared to Form 3 and parent RLZ indicates its potential use as a prolonged form."

Journal

GRIN2A alterations in primary CNS neoplasms: a case series (SNO 2025) - "Five patients received memantine over the course of their treatment for other indications, 1 ketamine, and 1 riluzole (for comorbid amyotrophic lateral sclerosis). GRIN2A alterations represent unique alterations in a subset of primary brain tumors. Analysis is ongoing regarding survival, functional significance, and presence of co-occurring somatic alterations."

Clinical • Tumor mutational burden • Amyotrophic Lateral Sclerosis • Brain Cancer • CNS Disorders • CNS Tumor • Melanoma • Solid Tumor • CDKN2A • GRIN2A • MGMT • MSH6 • TMB

Factors associated with overall survival in patients with motoneuron disease and respiratory symptoms (BTS WM 2025) - "Age, sex, riluzole use or comorbidities did not affect OS (all p>0.05). Discussion It is important to distinguish patients with ALS and non-ALS MND, as the former is associated with worse prognosis, especially in bulbar-onset subtype. LT-NIV is associated with survival benefit in patients with hypercapnia."

Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Respiratory Diseases

Comparative safety analysis of Riluzole, Edaravone and Tofersen in ALS management: insights from FAERS database. (PubMed, Front Pharmacol) - "This comprehensive evaluation underscores the importance of understanding the distinct AE profiles of Riluzole, Edaravone, and Tofersen in clinical practice, providing valuable insights for personalized ALS management. Future research with rigorous prospective designs is recommended to validate these findings and explore the mechanisms underlying the reported adverse events."

Journal • Amyotrophic Lateral Sclerosis • Cardiovascular • CNS Disorders • Hematological Disorders • Pain • Thrombosis • MMP9

When the Body Falls Silent: A Case Report of Amyotrophic Lateral Sclerosis. (PubMed, Cureus) - "The patient subsequently began follow-up with a multidisciplinary team encompassing the various domains of ALS management over the following 17 months. Riluzole therapy was initiated...This case highlights the devastating impact of early-onset ALS and underscores the importance of maintaining clinical suspicion when evaluating adults presenting with progressive neuromuscular symptoms. The rapid disease progression and associated psychosocial burden emphasize the critical role of multidisciplinary management, early palliative integration, and strong primary care involvement in optimizing patient and family support."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Respiratory Diseases

Total Reversal of ALS Confirmed by EMG Normalization, Structural Reconstitution, and Neuromuscular-Molecular Restoration Achieved Through Computerized Brain-Guided Reengineering of the 1927 Nobel Prize Fever Therapy: A Case Report. (PubMed, Diseases) - "This case provides the first documented evidence that ALS can be reversed through digitally reengineered fever therapy aligned with thermoregulation, which induces heat shock response and upregulates heat shock proteins, resulting in the patient no longer meeting diagnostic criteria for ALS and discontinuation of ALS-specific medications. Beyond ALS, shared protein-misfolding pathology suggests that CBIT2 may extend to Alzheimer's, Parkinson's, and related disorders. By modernizing this Nobel Prize-recognized therapeutic principle with computerized precision, CBIT2 establishes a framework for large-scale clinical trials. A century after fever therapy restored lost brain function and so decisively reversed dementia paralytica such that it earned the 1927 Nobel Prize in Medicine, CBIT2 now safely harnesses the therapeutic power of fever through noninvasive, intelligent, brain-guided thermal modulation."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Infectious Disease • Movement Disorders • Parkinson's Disease • IL10

Tuina combined with Riluzole in amyotrophic lateral sclerosis: protocol for a randomized controlled trial with clinical outcomes and synaptic PET biomarkers. (PubMed, Front Neurol) - P=N/A | "The findings are expected to provide evidence for integrating Tuina as an adjunctive, non-pharmacological therapy into comprehensive ALS management, linking functional improvements to underlying synaptic mechanisms. https://www.chictr.org.cn, identifier ChiCTR2300068650."

Biomarker • Clinical data • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

Large-scale drug screening in iPSC-derived motor neurons from sporadic ALS patients identifies a potential combinatorial therapy. (PubMed, Nat Neurosci) - "Combinatorial testing of effective drugs identified baricitinib, memantine and riluzole as a promising therapeutic combination for SALS. These findings demonstrate that patient-derived iPSC models can recapitulate sporadic disease features, paving the way for a new generation of disease modeling and therapeutic discovery in ALS."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

Riluzole as a Dual-Targeted Radiosensitizer for Osteosarcoma: Targeting Tumor Cells and Angiogenic Vasculature to Enhance Single High Dose Radiotherapy Efficacy. (PubMed, bioRxiv) - "It also suppresses tumor cell VEGFA expression, which may contribute to reduced pro-survival signaling in the angiogenic endothelial cells within the tumor microenvironment. Together, these effects sensitize osteosarcoma tumors to SDRT, improving therapeutic outcomes (Illustration created using BioRender (BioRender.com, 2025))."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Amyotrophic lateral sclerosis in Saudi Arabia: a multicenter descriptive study. (PubMed, Amyotroph Lateral Scler Frontotemporal Degener) - "Prespecified variables included demographics, family history, initial phenotype, MRI/EMG, genetics, treatments (riluzole, edaravone, SPT, tofersen for SOD1), times to noninvasive ventilation (NIV), gastrostomy and invasive ventilation. The younger age of onset and the high familial prevalence are notable findings that warrant further investigation. Future studies focusing on genetic and environmental influences in Saudi Arabia may help improve diagnosis and therapeutic approaches."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies

Targeting the core: C9ORF72 antagonists as pioneers in amyotrophic lateral sclerosis therapy-a computational and machine learning based approach. (PubMed, In Silico Pharmacol) - "Using Edaravone and Riluzole as benchmark molecules, the study evaluated various chemical compounds from different databases against the target...MD simulation concluded that the lead complexes showed lesser deviation and fluctuations with the higher number of hydrogen bond interactions which favors the structural stability and biological activity of the complex. This study concluded that the resultant leads from three different chemical libraries were considered as the potential therapeutic option for targeting ALS."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Infectious Disease

EGR1 Mediates Riluzole-Induced Apoptosis in Osteosarcoma via the Yap/p73-Bax Signaling Axis. (PubMed, bioRxiv) - "Together, these findings reveal a novel mechanism where Riluzole promotes apoptosis through upregulation of EGR1 , which then cooperates with YAP/p73 to activate Bax expression. These insights establish Riluzole as a promising therapeutic intervention for OS treatment through modulation of the EGR1 /Yap/p73/Bax signaling axis."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • ABL1 • BAX • CASP3 • EGR1

Cutting-edge treatments in amyotrophic lateral sclerosis: the role of molecular pathogenesis in targeted therapies. (PubMed, Stem Cell Res Ther) - "While current FDA-approved treatments such as Riluzole and Edaravone offer only modest benefits and do not significantly halt disease progression...However, several challenges remain, including effective delivery methods, safety concerns, and the inherent complexity of ALS pathology, ongoing research continues to explore these innovative interventions with the goal of improving clinical outcomes for patients. This review highlights the importance of personalized therapeutic approaches and underscores the necessity of continued innovation in ALS research, with the ultimate goal of developing disease-modifying therapies and, potentially, a cure for this fatal condition."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies • Inflammation • Metabolic Disorders • FUS • TARDBP

Genetic and Molecular Pathomechanisms of Amyotrophic Lateral Sclerosis and Therapeutic Perspectives – Current State of Knowledge (PubMed, Postepy Biochem) - "In addition, current therapeutic strategies are reviewed, including both registered drugs, such as riluzole and edaravone, and modern approaches, such as gene therapy, antisense oligonucleotides, immunotherapy and gene editing technologies, including CRISPR/Cas9. Special attention was given to clinical trials and their potential impact on future treatment options for ALS."

IO biomarker • Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies • Metabolic Disorders • Respiratory Diseases • FUS • SOD1 • TARDBP

GRIN2A alterations in primary CNS neoplasms: a case series (WFNOS 2025) - "Five patients received memantine over the course of their treatment for other indications, 1 ketamine, and 1 riluzole (for comorbid amyotrophic lateral sclerosis). GRIN2A alterations represent unique alterations in a subset of primary brain tumors. Analysis is ongoing regarding survival, functional significance, and presence of co-occurring somatic alterations."

Clinical • Tumor mutational burden • Amyotrophic Lateral Sclerosis • Brain Cancer • CNS Disorders • Melanoma • Oncology • Solid Tumor • CDKN2A • GRIN2A • MGMT • MSH6 • TMB

A meaningful prediction of functional decline in amyotrophic lateral sclerosis based on multi-event survival analysis. (PubMed, PLoS One) - "In this regard, we find that Riluzole has little or no impact on predicted functional decline. However, for patients with bulbar-onset ALS, our model predicts significantly shorter time-to-event estimates for loss of speech and swallowing function compared to patients with limb-onset ALS (log-rank p < 0.001, Bonferroni-adjusted [Formula: see text]). The proposed method can be applied to current clinical examination data to assess the risk of functional decline and thus allow more personalized treatment planning."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

Drug repurposing for Alzheimer's disease: a Delphi consensus and stakeholder consultation. (PubMed, Alzheimers Res Ther) - "This Delphi consensus identified three high-priority drug repurposing candidates for AD with favourable safety profiles and mechanistic plausibility, which are considered suitable for pragmatic clinical trials, including remote or hybrid designs. The PROTECT platform, which supports international cohorts in the UK, Norway, and Canada, offers a well-established means to conduct such trials effectively, thus helping to accelerate the evaluation and potential deployment of these drug candidates to benefit individuals with or at risk for AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Herpes Zoster • Varicella Zoster

Anti-inflammatory therapeutic strategies for treating spinal cord injury (Neuroscience 2025) - "Pharmacologic inhibitors such as TNF-α antagonists and riluzole have shown neuroprotective effects, though clinical translation remains under investigation...Future research should prioritize combinatorial therapies, controlled delivery systems, and a better understanding of immune dynamics during acute and chronic SCI phases. This review underscores the importance of ongoing investigation into targeted immune modulation as a cornerstone of effective spinal cord injury treatment."

CNS Disorders • IL10 • IL4

Life extension, motoneuronal excitability, and extrasynaptic glutamate: the role of system xc- in amyotrophic lateral sclerosis (Neuroscience 2025) - "Due to the availability of FDA-approved system xc- inhibitors, our results portend high translational potential for ameliorating ALS pathology in humans. Furthermore, these studies warrant future investigations comparing and/or combining system xc- antagonism with current therapies, such as Riluzole treatment."

Amyotrophic Lateral Sclerosis • CNS Disorders • Depression • Psychiatry

Loss-of-function and toxic gain-of-function of TDP43 in an in vitro model of amyotrophic lateral sclerosis (Neuroscience 2025) - "Neurotoxicity and TDP43 pathology were mitigated in the presence of Riluzole, a FDA-approved drug for the management of ALS. In the second experiment, the application of TDP43-PFFs on healthy spinal MNs lead to a time- and concentration-dependent neurotoxicity, associated with a loss of neurites. Altogether, these findings demonstrate that in vitro models of ALS, based on primary spinal MNs, are valuable tools for modelling ALS, as they reproduce the TDP43 loss-of-function, due to its sequestration in the cytoplasm, and the TDP43 toxic gain-of-function that are key features of ALS."

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Proteinopathy • TARDBP

Drug screening for upregulation of BDNF expression revealed novel drugs and drug target interactions in vitro. (Neuroscience 2025) - "Amongst 1581 compounds tested, we identified 125 molecules that significantly upregulated BDNF promoter activity when compared to Riluzole, a drug used to treat amyotrophic lateral sclerosis (ALS) and known to upregulate BDNF expression...The extent of neurite outgrowth positively correlated with BDNF expression level upregulated by the drugs in the SH-SY5Y. We will further explore the functional mechanism through which these 7 compounds upregulate BDNF expression cooperatively, and therapeutic significance of these drugs."

Preclinical • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Movement Disorders • Parkinson's Disease • BDNF

Markers of presymptomatic amyotrophic lateral sclerosis: State of the art, practical implications and perspectives. (PubMed, Rev Neurol (Paris)) - "While riluzole remains the standard treatment, mutation-specific therapies such as tofersen, that was recently approved in SOD1-ALS, are emerging. These biomarkers may support early surveillance and intervention strategies. The present review provides an overview of current evidence on presymptomatic biomarkers in ALS mutation carriers and their potential role in genetic counseling, monitoring, and early therapeutic decisions."

Biomarker • Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • NEFL • Plasma NfL • SOD1

Validation in Drosophila of the in silico predicted clomipramine as repurposable for SOD1-ALS. (PubMed, Neurotherapeutics) - "Current Food and Drug Administration-approved drugs -riluzole, edaravone, and tofersen - offer limited clinical benefit due to ALS multifactorial etiology and high heterogeneity...Leveraging the SAveRUNNER algorithm, we identified several potentially repurposable candidates, including clomipramine (Anafranil®), mianserin (Lantanon®/Tolvon®), and modafinil (Provigil®)...Our results demonstrate that clomipramine is the most promising candidate, ameliorating lifespan reduction, improving climbing abilities, and mitigating both genomic instability and inflammation, key pathological hallmarks of these SOD1-ALS models. Despite needing further validation in higher organisms, our Drosophila findings represent preliminary yet significant support for clomipramine's action as an add-on treatment for SOD1-ALS."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • Respiratory Diseases

Loss-of-function and toxic gain-of-function of TDP43 in an in vitro model of amyotrophic lateral sclerosis (ALS-MND 2025) - "Neurotoxicity and TDP43 pathology were mitigated in the presence of Riluzole, a FDA-approved drug for the management of ALS. In the second experiment, the application of TDP43-PFFs on healthy spinal MNs lead to a time- and concentration-dependent neurotoxicity, associated with a loss of neurites. Altogether, these findings demonstrate that in vitro models of ALS, based on primary spinal MNs, are valuable tools for modeling ALS, as they reproduce the TDP43 loss-of-function, due to its sequestration in ß 2024 World Federation of Neurology on behalf of the Research Group on Motor Neuron the cytoplasm, and the TDP43 toxic gain-of-function that are key features of ALS."

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Proteinopathy • TARDBP