GENE THERAPY AS A NEW INNOVATION IN CHRONIC PAIN MANAGEMENT IN CANCER PATIENTS
Mostafa Mohamed El Adany;
Abstract
Some forms of chronic pain, in particulal" those of nemopathic origin, remain unsatisfactorily managed with cmrently available
Summary
pharmacological agents, some of which, in addition, may be poorly tolerated by some patients. Although some targets, such as the neurokinin I receptor, were identified as promising for pain treatment, the development of relevant pharmacological tools ended in disappointing clinical results, new therapeutic approaches also exploring novel potentially interesting targets are clearly needed.
Modifications in the expression of a series of key molecules involved in the processing of nociceptive signals are thought to participate in pain perpetuation. Gene-based approaches offer the possibility to modulate the synthesis of some of these proteins in selected relevant structmes. This aims at either an in-situ production of therapeutic proteins or, conversely, the suppression of 'pain inducing' proteins . The successful transfer and overexpression of opioid precmsor genes at the spinal level by using virus-derived vectors has opened the way for protocols attempting to alleviate experimental porsistent pain in anintals
The notion of a foreign DNA sequence as a somce of therapeutic protein introduced (or re-introduced) into an organism is now widely accepted. That a transgene-detived protein, synthesised in a closely targeted stmctme or cell group, would act directly or in the near vicinity of cells appeared as a tempting possibility. Such an approach might circumvent some problems of 'classical' dmgs, such as an inadequate half-life or undesirable side effects. In addition, nucleic acid transfer approaches also offer the possibility to reduce the expression of genes by using the DNA sequences in antisense otientation or the more recently described short interfering RNAs
Various techniques allowing the in vivo tl"ansfer of DNA sequences are available. Some were experimented in various structmes and tissues in relation with chronic pain. So far available data suppmt the idea that virus-derived vectors are the most potent systems enabling
sustained (and even long lasting v.-ith appropriate promoters) synthesis of transgene-detived products Due to its biological characteristics, herpes simplex virus (HSV) type I is among the most suitable vectors for the specific targeting of the peripheral nervous system and particularly ptimary sens01y nemones . This vector offers the possibility of introducing transgenes into the sensory ganglia
following non-invasive peripheral application.
Summary
pharmacological agents, some of which, in addition, may be poorly tolerated by some patients. Although some targets, such as the neurokinin I receptor, were identified as promising for pain treatment, the development of relevant pharmacological tools ended in disappointing clinical results, new therapeutic approaches also exploring novel potentially interesting targets are clearly needed.
Modifications in the expression of a series of key molecules involved in the processing of nociceptive signals are thought to participate in pain perpetuation. Gene-based approaches offer the possibility to modulate the synthesis of some of these proteins in selected relevant structmes. This aims at either an in-situ production of therapeutic proteins or, conversely, the suppression of 'pain inducing' proteins . The successful transfer and overexpression of opioid precmsor genes at the spinal level by using virus-derived vectors has opened the way for protocols attempting to alleviate experimental porsistent pain in anintals
The notion of a foreign DNA sequence as a somce of therapeutic protein introduced (or re-introduced) into an organism is now widely accepted. That a transgene-detived protein, synthesised in a closely targeted stmctme or cell group, would act directly or in the near vicinity of cells appeared as a tempting possibility. Such an approach might circumvent some problems of 'classical' dmgs, such as an inadequate half-life or undesirable side effects. In addition, nucleic acid transfer approaches also offer the possibility to reduce the expression of genes by using the DNA sequences in antisense otientation or the more recently described short interfering RNAs
Various techniques allowing the in vivo tl"ansfer of DNA sequences are available. Some were experimented in various structmes and tissues in relation with chronic pain. So far available data suppmt the idea that virus-derived vectors are the most potent systems enabling
sustained (and even long lasting v.-ith appropriate promoters) synthesis of transgene-detived products Due to its biological characteristics, herpes simplex virus (HSV) type I is among the most suitable vectors for the specific targeting of the peripheral nervous system and particularly ptimary sens01y nemones . This vector offers the possibility of introducing transgenes into the sensory ganglia
following non-invasive peripheral application.
Other data
| Title | GENE THERAPY AS A NEW INNOVATION IN CHRONIC PAIN MANAGEMENT IN CANCER PATIENTS | Authors | Mostafa Mohamed El Adany | Issue Date | 2005 |
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