In an effort to find a more effective treatment for chronic pain, researchers at Mount Sinai developed a gene therapy technique that simulates the pain-killing effect of opiate drugs. In the new study Sensory neuron targeting by self-complementary AAV8 via lumbar puncture for chronic pain published in the January 22, 2008 issue of the Proceedings of the National Academy of Sciences (PNAS), researchers suggest that gene therapy for pain might in the future become a treatment alternative for patients with severe chronic pain.
Fifty million Americans suffer from chronic pain. Chronic pain patients often do not experience satisfactory pain relief from available treatments due to poor efficacy or intolerable side effects like extreme sleepiness, mental clouding, and hallucinations, said Dr. Andreas Beutler, MD, principal investigator of the study and Assistant Professor of Medicine/ Hematology And Medical Oncology at Mount Sinai School of Medicine.
Mount Sinai researchers designed a viral vector to carry the prepro-b-endorphin gene into primary sensory neurons in order to activate opiate receptors selectively, in a rat model. The agents were delivered directly into the spinal fluid of rats via a lumbar puncture, or spinal tap with only one injection. Results showed that the rats remained symptom-free for an extended period of time.
Our research found that treating chronic pain with Adeno-Associated Virus vector-based gene therapy allows for pain relief for more than three months after a single injection, targeting selectively the pain gate. The technique worked successfully with opioid- and non-opioid therapeutic genes, said Dr. Beutler. Targeted gene therapy will likely avoid the unwanted side effects associated with opioid painkillers such as morphine. Based on our findings, this targeted gene therapy via lumbar puncture appears to be a promising candidate for bench-to-bedside research that might ultimately be tested in patients with intractable chronic pain, e.g., to help patients suffering from severe pain due to advanced cancer.
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For chemotherapy, this system could enhance treatment efficacy while preventing uncontrolled delivery and the resultant patient side effects, Ho said. Furthermore, as implantable devices continue to find widespread application in cardiovascular medicine, neural disorders and diabetes, the nano-cloaking capabilities can serve as a widely applicable approach to enhance the lifetime of these devices. This would eliminate unnecessary surgeries and enhance the efficiency of patient care.
Many cancer drugs, chemotherapies for example, are delivered systemically through the blood stream. The drugs attack cancer cells, but also other fast growing cells causing side effects such as anemia, nausea and hair loss. If the chemotherapy could be delivered by implant directly to the tumor site, such side effects would be limited, said Cheng, who also is a member of the Center for Cell Control at the UCLA Henry Samueli School of Engineering and Applied Sciences.
Say you have a localized cancer such as breast cancer, the drugs we give are not directly targeted to the breast, Cheng said. If we could apply the treatment locally and control the release of the drugs, the therapy might be more effective in treating the cancer.
Chemotherapy drugs could potentially be placed in high concentration between the polymer films and an implant placed at the tumor site. The drugs would be released slowly, over time, delivering more of the toxic chemicals directly to the cancer cells.
This study provided the proof of principle that implants in animal models could be coated with materials that made them invisible to the immune system. Cheng and Ho are now testing in animal models whether cancer therapies can be effectively and safely administered and locally delivered using the nanomaterials.
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