He noted that treatment with topical p53 has been investigated in national and international clinical trials. Although the treatment may be effective, one obstacle is the delivery system: it has to be directly injected into the lesion, and the injection doesn’t transfer enough genes into enough cells to make a distinct lasting difference, he said. Once the delivery has been improved, gene therapy will be more successful.
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September 2006Dr. Clayman concurred with Dr. O’Malley that the premalignant setting in a topical formulation is another promising application for p53. As a cancer therapy or preventive agent, p53 seems to work on multiple levels, but its key properties in these settings are its ability to induce apoptosis and to inhibit angiogenesis in malignant cells, Dr. Clayman said.
Hearing Loss and Gene Therapy
No gene therapy has yet been approved for genetically influenced disorders typically seen in otolaryngology offices, Dr. Clayman said.
For hearing loss and balance disorders, the ideal would be to introduce a gene that regenerates hair cells, Dr. O’Malley said. The MATH-1 gene has been studied and shown promise in hair cell generation in animals and cell culture. This is exciting, because hearing loss is a big problem. There is also the possibility of genetic transfer to the ear to prevent the type of hearing loss seen in chemotherapy, which destroys hair cells. This would be a protective protein to prevent hair loss. In a different field, MATH-1 gene therapy or nerve growth factor gene therapy may help with nerve and muscle regeneration in patients with surgically induced damage to the ear, larynx, facial nerves, or other anatomical sites that are often treated by otolaryngologists.
Another issue that could be improved with gene therapy is genetically influenced deafness after treatment with aminoglycosides or certain cancer chemotherapies. In the event that a corrective gene or even a gene that produces a preventative agent for hearing loss could be found, the gene therapy could be given prior to treatment rather to prevent the hearing loss. New classes of antibiotics not developing right now, Dr. O’Malley said. We need to look at other means of dealing with these problems rather than a new antibiotic.
©2006 The Triological Society