Viral and non-viral gene therapy partially prevents experimental cisplatin-induced neuropathy

Pf, Pradat; Kennel, Philippe; S, Naimi-Sadaoui; Finiels, Françoise; Scherman, Daniel; Orsini, Cécile; Delaère, P.; Mallet, Jacques; Revah, Frédéric

doi:10.1038/sj.gt.3301801

Cited by 33 publications

(14 citation statements)

References 27 publications

(40 reference statements)

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“…A recovery from a dorsal rhizotomy or a dorsal column lesion is still at the experimental level. It most probably needs the concomitant transgene-mediated, continuous overexpression of high levels of neurotrophins at the lesion site [81], plus additional measures such as transforming the DRG neuron cells to a competence for regrowth or counteracting the growthinhibitory nature of the CNS tissue.…”

Section: Discussionmentioning

confidence: 99%

Regeneration of Primary Sensory Neurons

Donnerer¹

2003

Pharmacology

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Primary sensory neurons have an inherent capacity for regeneration of their cut, crushed, or chemically lesioned axons. This capacity is displayed to a much greater extent after lesions of the peripheral axons than after lesions of their centrally directed axons. Additionally, the surrounding tissue determines to a significant extent the degree of recovery: whereas the peripheral nerve tissue provides neurotrophic support and a favorable environment for axonal growth, the central terminals of primary sensory neurons face a non-permissive and inhibitory glial tissue. Mechanical lesions of the peripheral axons of dorsal root ganglion (DRG) sensory neurons can be repaired by the intrinsic regenerative capacity of the neuron itself, when outgrowing axons from the proximal stump are able to transverse the tissue scar and reach the distal stump of the nerve. Bridging the gap with an autologous nerve graft or a short artificial graft filled with nerve growth factor (NGF) can improve recovery. Neurotoxic lesions of the axon terminals are effectively recovered by intermittent local or systemic NGF injections. A recovery from a diabetic sensory neuropathy probably requires the continuous delivery of NGF or additional neurotrophic factors. A recovery from a dorsal rhizotomy or from a dorsal column lesion can possibly be achieved by the concomitant transgene-mediated overexpression of neurotrophins, the transformation of the DRG neuron cells to a competence for regrowth, and the counteraction of the growth-inhibitory nature of the central nervous system tissue.

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Section: Discussionmentioning

confidence: 99%

Regeneration of Primary Sensory Neurons

Donnerer¹

2003

Pharmacology

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“…In several different models, i.m. injection of a lipid-encapsulated plasmid, or adenoviral or adeno-associated viral vectors coding for a neurotrophic or neuroprotective peptide, has been shown to prevent the progression of neuropathy resulting from the administration of neurotoxic drugs or from diabetes [15][16][17] up to 6 weeks.…”

mentioning

confidence: 99%

Prolonged preservation of nerve function in diabetic neuropathy in mice by herpes simplex virus-mediated gene transfer

Chattopadhyay¹,

Mata²,

Goss³

et al. 2007

Diabetologia

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Aims/hypothesis The aim of this study was to determine whether prolonged expression of neurotrophin-3 (NT-3) in mice, achieved by herpes simplex virus (HSV)-mediated gene transfer with gene expression under the control of an HSV latency promoter, can provide protection against the progression of diabetic neuropathy over a 6 month period. Materials and methods Mice with diabetes induced by streptozotocin were inoculated s.c. into both hind feet with a non-replicating HSV vector containing the coding sequence for NT-3 under the control of the HSV latencyassociated promoter 2 (LAP2) elements or with a control vector. Nerve function was evaluated by electrophysiological and behavioural measures over the course of 6 months after the onset of diabetes. Results Animals inoculated with the NT-3-expressing vector, but not animals inoculated with control vector, showed preservation of sensory and motor nerve amplitude and conduction velocity measured electrophysiologically, small fibre sensory function assessed by withdrawal from heat, autonomic function measured by pilocarpine-induced sweating, skin innervation assessed by protein gene product 9.5 staining of axons, and density of calcitonin gene-related peptide terminals in the spinal cord measured by immunohistochemistry 5.5 months after vector inoculation. Conclusions/interpretation These results indicate that the continuous production of NT-3 by LAP2-driven expression of the transgene from an HSV vector over a 6 month period protects against progression of diabetic neuropathy in mice, and provide a proof-of-principle demonstration for the development of a novel therapy for preventing the progression of diabetic neuropathy.

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“…47,109 Cisplatin-induced neuropathy also was blocked by treatment with neurotrophic factor, the ACTH4-9 analog ORG 2766, 36,56 and recombinant human glial growth factor 2, 162 and the survival of large-fiber sensory neurons can be induced by administration of neurotrophin 3. 135 Although cisplatin-induced neuropathy progressed for 6 wk after discontinuation of the drug and slowly reversed over 3 mo, this side effect could be prevented by early decompressive surgery. 161 Models of pain from spontaneous cancer A natural model of cancer pain involves using animals that have spontaneously occurring tumors.…”

Section: Discussionmentioning

confidence: 99%

Animal Models of Cancer Pain

Pacharinsak

Beitz²

2010

Animal Models of Pain

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220Pain is one of the most common and distressing symptoms experienced by both human and veterinary oncology patients with advanced cancer. In humans, unrelieved pain can disrupt and interfere with activities of daily living, quality of life, and mood, 26,173 and domestic animals typically are euthanized when pain is no longer adequately controlled. 138 New developments in cancer detection and therapy have occurred over the past decade. These developments are contributing to longer life expectancies and have raised important issues related to quality of life, as attention has focused increasingly on how to manage cancer pain effectively. 91,115,134 This increased attention is true in the fields of both human and veterinary medicine. Human cancer patients who are in advanced stages of the disease, particularly those with bone metastasis, report that they experience significant pain, and pain intensity appears to be related to the degree of bone destruction. Similarly, pain secondary to cancer in domestic animals is a key concern in veterinary practice and should be addressed promptly to alleviate suffering, stress, and anxiety and to improve quality of life. Not only do cancer patients have to deal with persistent pain, they also often experience 'breakthrough pain.' Breakthrough pain-intermittent episodes of extreme pain-occurs spontaneously or after movement or weight-bearing of the affected leg. 114,133 Canine osteosarcoma has many clinical and biological similarities to human osteosarcoma, and affected dogs show signs of both ongoing and breakthrough pain. 37 In addition to cancer-induced pain, human patients also experience pain caused by the very therapies used to treat the cancer. Almost 30% of adult cancer patients and 60% of pediatric cancer patients who have undergone treatments that include radiation, chemotherapy, or surgery also have experienced pain resulting from these therapeutic procedures. 49,174 Whether radiation treatment and chemotherapy also induce pain in domestic animals is virtually impossible to address, because carefully controlled studies have not examined this issue.Pain intensity varies among cancer patients and is dependent on a patient's pain sensitivity, the type of cancer, and the tumor location. 48,49 Cancer treatment guidelines provided by the World Health Organization have been used in oncology and pain treatment clinics. 20,25,92,113,117,119,163 Treatment of human cancer patients include the use of opioids, nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, local anesthetics, antidepressants, and anticonvulsants either alone or in combination. Similarly in veterinary medicine, the goal of palliative therapy in cancer patients is to control pain from an incurable tumor and to support overall quality of life. 165 Therefore, opioids, NSAIDs, and bisphosphonates are used in addition to surgery and radiation therapy and are the drugs of choice in treating domestic animals with cancer pain, particularly those suffering from osteosarcoma and other forms of bone cancer. 1...

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Viral and non-viral gene therapy partially prevents experimental cisplatin-induced neuropathy

Cited by 33 publications

References 27 publications

Regeneration of Primary Sensory Neurons

Regeneration of Primary Sensory Neurons

Prolonged preservation of nerve function in diabetic neuropathy in mice by herpes simplex virus-mediated gene transfer

Animal Models of Cancer Pain

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