Ultrasound Therapy and Therapeutic Exercise for Chemotherapy Induced Peripheral Neuropathy (CIPN)
Ontology highlight
ABSTRACT:
DISEASE(S): Colon Neoplasms,Peripheral Nervous System Diseases,Colorectal Neoplasms,Colonic Neoplasms,Neoplasms
PROVIDER: 2194292 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:This pilot clinical trial studies how well ultrasound works in detecting oxaliplatin-induced neuropathy in patients with gastrointestinal cancer. Ultrasound may work better in diagnosing and detecting neuropathy in gastrointestinal cancer patients treated with the chemotherapy drug called a oxaliplatin.
| 2306231 | ecrin-mdr-crc
Project description:Objective Repeat expansion mutations underlie diverse neurogenetic disorders, many involving the peripheral nervous system. Despite peripheral neuropathy being the most common neurological disorder worldwide, its contribution to repeat expansion diseases remains poorly defined, and robust preclinical models are limited. We established a translational framework to study peripheral neuropathy in Spinocerebellar ataxia type 3 (SCA3), a fatal multisystem disorder caused by a pathogenic CAG expansion in ATXN3. Methods SCA3 Knock-In Atxn3Q300/Q6 (KI) and Atxn3-/- Knock-Out (KO) mice underwent sensorimotor nerve conduction and behavioral testing. Peripheral tissues were evaluated for SCA3-related pathology, and transcriptional changes in KI dorsal root ganglia (DRG) were assessed by bulk RNA sequencing. To test therapeutic relevance, we generated a conditional “OFF” SCA3 knock-in (cKI) mouse and crossed it with Avil-Cre to selectively silence mutant ATXN3 in sensory neurons. Peripheral phenotyping was repeated in Avil-Cre; cKI mice. Results KI mice developed progressive sensorimotor deficits, peripheral histopathology, and RNA splicing dysregulation that parallel clinical features of SCA3. In contrast, KO mice showed normal peripheral nerve function, implicating toxic gain-of-function from mutant ATXN3 as the causative driver. Sensory neuron–specific silencing of mutant ATXN3 significantly ameliorated peripheral nerve abnormalities. Interpretation These findings define a pathogenic role for repeat expansion–driven peripheral nerve degeneration in SCA3, identify sensory neurons as key therapeutic targets, and provide a preclinical platform for developing peripheral interventions in SCA3 and related repeat expansion disorders.
2026-05-11 | GSE320015 | GEO
Project description:Objective Repeat expansion mutations underlie diverse neurogenetic disorders, many involving the peripheral nervous system. Despite peripheral neuropathy being the most common neurological disorder worldwide, its contribution to repeat expansion diseases remains poorly defined, and robust preclinical models are limited. We established a translational framework to study peripheral neuropathy in Spinocerebellar ataxia type 3 (SCA3), a fatal multisystem disorder caused by a pathogenic CAG expansion in ATXN3. Methods SCA3 Knock-In Atxn3Q300/Q6 (KI) and Atxn3-/- Knock-Out (KO) mice underwent sensorimotor nerve conduction and behavioral testing. Peripheral tissues were evaluated for SCA3-related pathology, and transcriptional changes in KI dorsal root ganglia (DRG) were assessed by bulk RNA sequencing. To test therapeutic relevance, we generated a conditional “OFF” SCA3 knock-in (cKI) mouse and crossed it with Avil-Cre to selectively silence mutant ATXN3 in sensory neurons. Peripheral phenotyping was repeated in Avil-Cre; cKI mice. Results KI mice developed progressive sensorimotor deficits, peripheral histopathology, and RNA splicing dysregulation that parallel clinical features of SCA3. In contrast, KO mice showed normal peripheral nerve function, implicating toxic gain-of-function from mutant ATXN3 as the causative driver. Sensory neuron–specific silencing of mutant ATXN3 significantly ameliorated peripheral nerve abnormalities. Interpretation These findings define a pathogenic role for repeat expansion–driven peripheral nerve degeneration in SCA3, identify sensory neurons as key therapeutic targets, and provide a preclinical platform for developing peripheral interventions in SCA3 and related repeat expansion disorders.
2026-05-11 | GSE320100 | GEO
Project description:Objective Repeat expansion mutations underlie diverse neurogenetic disorders, many involving the peripheral nervous system. Despite peripheral neuropathy being the most common neurological disorder worldwide, its contribution to repeat expansion diseases remains poorly defined, and robust preclinical models are limited. We established a translational framework to study peripheral neuropathy in Spinocerebellar ataxia type 3 (SCA3), a fatal multisystem disorder caused by a pathogenic CAG expansion in ATXN3. Methods SCA3 Knock-In Atxn3Q300/Q6 (KI) and Atxn3-/- Knock-Out (KO) mice underwent sensorimotor nerve conduction and behavioral testing. Peripheral tissues were evaluated for SCA3-related pathology, and transcriptional changes in KI dorsal root ganglia (DRG) were assessed by bulk RNA sequencing. To test therapeutic relevance, we generated a conditional “OFF” SCA3 knock-in (cKI) mouse and crossed it with Avil-Cre to selectively silence mutant ATXN3 in sensory neurons. Peripheral phenotyping was repeated in Avil-Cre; cKI mice. Results KI mice developed progressive sensorimotor deficits, peripheral histopathology, and RNA splicing dysregulation that parallel clinical features of SCA3. In contrast, KO mice showed normal peripheral nerve function, implicating toxic gain-of-function from mutant ATXN3 as the causative driver. Sensory neuron–specific silencing of mutant ATXN3 significantly ameliorated peripheral nerve abnormalities. Interpretation These findings define a pathogenic role for repeat expansion–driven peripheral nerve degeneration in SCA3, identify sensory neurons as key therapeutic targets, and provide a preclinical platform for developing peripheral interventions in SCA3 and related repeat expansion disorders.
2026-05-11 | GSE329323 | GEO
Project description:Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of cancer treatment, yet the lack of predictive human models has hindered therapeutic progress. We have established a scalable model of paclitaxel-induced axon degeneration and neurotoxicity in iPSC-derived sensory neurons, suitable for high-throughput discovery of neuroprotective compounds. Using this platform, we screened 192 kinase inhibitors and identified 19 hits that commonly inhibited three STE20 kinases - MAP4K4, MINK1, and TNIK. Genetic knockdown revealed that multi-kinase inhibition of STE20 kinases is required for neuroprotection against paclitaxel. Moreover, selective pharmacological inhibition of STE20 kinases rescued paclitaxel-induced axon degeneration in iPSC-derived sensory neurons and primary human DRG, as well as preserved intraepidermal nerve fiber density in a mouse model of CIPN. These results establish a translational human sensory neuron platform for target and drug discovery in CIPN.
2026-04-03 | PXD074954 | Pride
Project description: Not available
| S-EPMC9469051 | biostudies-literature
Project description:Paclitaxel-induced peripheral neuropathy is a significant problem, which afflicts up to 70% of chemotherapy patients. Therapeutic interventions are currently unavailable due to an incomplete understanding of the underlying mechanisms. We previously discovered a major target in the skin, MMP-13, which underlies the development of paclitaxel-induced peripheral neuropathy in zebrafish and rodents. To better understand gene expression changes in sensory neurons and target tissue prior to and during the progression of neuropathy, we performed longitudinal RNA sequencing of mouse skin and dorsal root ganglion (DRG) neurons. Samples were harvested at time points associated with behavioural responses following injection of mice for 7 days either with vehicle or paclitaxel. The responses were categorized into pain onset (day 4 of paclitaxel injection), maxima (d7), beginning of pain resolution (d11) and recovery phase (d23). This dataset will be useful to understand changes in gene regulation in both neurons and skin, which can aid in the discovery of therapeutic interventions.
2021-10-12 | GSE185084 | GEO
Project description:Genetic pain loss disorders represent a heterogeneous group of rare diseases mainly characterized by defective nociception. Understanding the underlying molecular mechanism is fundamental to improve the treatment of patients affected by these rare disorders. Feline Leukemia Virus Subgroup C Receptor 1 (FLVCR1) is one of the genes previously associated with sensory neuropathy that require further investigation. Here, we report on two additional patients with novel disease-causing variants in FLVCR1 and introduce a zebrafish model of the disease. The analyses of patient-derived fibroblasts showed that distinct FLVCR1 variants compromised all the known functions associated with FLVCR1, thus affecting choline levels, heme biosynthesis and mitochondrial Ca2+ handling. Furthermore, we provide evidence that the alteration of these processes impairs TCA cycle and OXPHOS, and induces lipid peroxidation. Our data points to the alterations of energetic metabolism as a potential driving pathomechanism in FLVCR1-associated sensory neuropathy.
2026-02-02 | PXD071580 | Pride
Project description: Not available
| S-EPMC5685301 | biostudies-literature
Project description:Oxaliplatin-induced chronic peripheral neuropathy is of major concern to oncologists and patients as it has been shown to affect patients’ health-related quality of life. Although a number of interventions have been implicated, none of them can be recommended for clinical use. This therapeutic failure reflects a poor understanding of the real mechanism of oxaliplatin-induced neuropathy. However, oxidative stress is identified to be one of the main biomolecular dysfunctions in this neuropathy. Rood’s approach is a neurophysiological approach that is based on reflexes of the central nervous system in which the sensory stimulation provides desired muscular response and was specially designed for patients with motor control problems. It was developed by Margeret Rood in 1940. According to Rood, sensory stimulation can activate or deactivate the receptor by facilitation or inhibition, which makes it possible to get the desired muscular response.
| 61819 | ecrin-mdr-crc