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06-22-2008, 03:01 PM | #1 | |||
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(seems researchers have been thinking about/looking into utilizing Ibogaine for PD
https://www.mcmp.purdue.edu:4443/sem...elabstract.pdf Benjamin Chemel September 6, 2005 GDNF and Ibogaine: Developing a Cure for Parkinson’s Disease Glial cell line-derived neurotrophic factor (GDNF) is a disulfide-linked, homodimeric protein that promotes the survival and morphological differentiation of midbrain dopamine neurons (7).The ability of GDNF to act as a growth factor for dopamine neurons suggests that it could be a valuable treatment for Parkinson’s Disease (PD), a debilitating neurodegenerative disorder caused by a loss of dopamine neurons in the substantia nigra. (5). The loss of dopaminergic neurons in PD leads to deficient levels of dopamine in the striatum and subsequent dysregulation of motor control. Current PD treatments, including methods of dopamine replacement, are limited to ameliorating symptoms. In contrast, an ideal therapeutic approach would aim to halt the progressive cell loss or improve function in spared neurons. It has been hypothesized that GDNF represents a neuroprotective and neurorestorative treatment for the symptoms and pathology of PD (3). In chemically induced animal models of PD, GDNF has demonstrated the safety and efficacy prerequisites for clinical trials in humans (2). Because this 134 amino acid protein cannot cross the blood brain barrier, new techniques are being developed to deliver GDNF into target tissues deep within the brain (1). One such approach, which employs an intraparenchymal catheter to infuse recombinant protein directly into the midbrain, was utilized in a recent phase I clinical trial (10). In this open-label trial, symptomatic evaluations were conducted using the Universal Parkinson’s Disease Rating Scale (UPDRS), while midbrain neuronal function was assessed using 18F-dopa positron emission tomography (PET) imaging. The results suggested that the long-term, continuous infusion of GDNF was well tolerated, with no apparent side effects. Additionally, all test subjects displayed a significant amelioration of their PD disease state. Improved motor skills and quality of life were correlated with increased function of midbrain dopaminergic neurons, as evidenced by 18F-dopa PET imaging. Additional molecular evidence suggested that neuronal sprouting may have contributed to this enhanced cellular activity (8). Phase II studies were aborted by the parent company, citing lack of functional improvements and safety concerns, yet for the patients and researchers involved, GDNF remains a promising treatment for PD. A pharmacological means of regulating endogenous GDNF could improve safety and delivery issues. One such compound is the hallucinogenic alkaloid, ibogaine. The ability of ibogaine to treat drug addiction and withdrawal has been anecdotally reported and verified in animal models of opiate, stimulant, and alcohol abuse (6). GDNF signaling is reportedly diminished by drugs of abuse (9), suggesting that GDNF may be involved in the attenuation of addiction by ibogaine (4). These observations provide evidence for my original hypothesis, that ibogaine represents a novel means of regulating GDNF and can be used to treat Parkinson’s Disease. In a recent study, ibogaine was found to upregulate GDNF expression in the midbrain and increase GDNF secretion and GDNF-dependent activation of downstream signaling pathways in vitro (4). These data suggest that ibogaine may represent a powerful new method to upregulate GDNF in the treatment of neurodegenerative disorders. Multidisciplinary research, using ibogaine as a lead compound, could reshape the lives of those afflicted with Parkinson’s Disease. References 1. Aebischer, P., and J. L. Ridet. 2001. Recombinant proteins for neurodegenerative diseases: the delivery issue. Trends In Neurosciences 24:533-540. 2. Bjorklund, A., and O. Lindvall. 2000. Parkinson disease gene therapy moves toward the clinic. Nature Medicine 6:1207-1208. 3. Grondin, R., and D. M. Gash. 1998. Glial cell line-derived neurotrophic factor (GDNF): a drug candidate for the treatment of Parkinson's disease. Journal Of Neurology 245:P35-P42. 4. He, D. Y., N. N. H. McGough, A. Ravindranathan, J. Jeanblanc, M. L. Logrip, K. Phamluong, P. H. Janak, and D. Ron. 2005. Glial cell linederived neurotrophic factor mediates the desirable actions of the antiaddiction drug ibogaine against alcohol consumption. Journal Of Neuroscience 25:619-628. 5. Kirik, D., B. Georgievska, and A. Bjorklund. 2004. Localized striatal delivery of GDNF as a treatment for Parkinson disease. Nature Neuroscience 7:105-110. 6. Levi, M. S., and R. F. Borne. 2002. A review of chemical agents in the pharmacotherapy of addiction. Current Medicinal Chemistry 9:1807-1818. 7. Lin, L. F. H., D. H. Doherty, J. D. Lile, S. Bektesh, and F. Collins. 1993. Gdnf - A Glial-Cell Line Derived Neurotrophic Factor For Midbrain Dopaminergic-Neurons. Science 260:1130-1132. 8. Love, S., P. Plaha, N. K. Patel, G. R. Hotton, D. J. Brooks, and S. S. Gill. 2005. Glial cell line-derived neurotrophic factor induces neuronal sprouting in human brain. Nature Medicine 11:703-704. 9. Messer, C. J., A. J. Eisch, W. A. Carlezon, K. Whisler, L. Shen, D. H. Wolf, H. Westphal, F. Collins, D. S. Russell, and E. J. Nestler. 2000. Role for GDNF in biochemical and behavioral adaptations to drugs of abuse. Neuron 26:247-257. 10. Patel, N. K., M. Bunnage, P. Plaha, C. N. Svendsen, P. Heywood, and S. S. Gill. 2005. Intraputamenal infusion of glial cell line-derived neurotrophic factor in PD: A two-year outcome study. Annals Of Neurology 57:298-302. 11. Sariola, H., and M. Saarma. 2003. Novel functions and signalling pathways for GDNF. Journal Of Cell Science 116:3855-3862.
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In the last analysis, we see only what we are ready to see, what we have been taught to see. We eliminate and ignore everything that is not a part of our prejudices. ~ Jean-Martin Charcot The future is already here — it's just not very evenly distributed. William Gibson Last edited by olsen; 06-22-2008 at 03:29 PM. |
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06-22-2008, 03:24 PM | #2 | |||
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http://thescientistblog.blogspot.com...to-act-on.html
"...A naturally occurring hallucinogen advocated by some clinicians as a potent anti-addiction drug has been rigorously studied for the first time, confirming its ability to block alcohol craving in rodents, and clarifying how it works in the brain. The new research findings about the drug Ibogaine open the way for development of other drugs to reverse addiction without Ibogaine's side effects, potentially adding to the small arsenal of drugs that effectively combat addiction. Derived from a West African shrub, Ibogaine has been championed for years by a cadre of clinicians and drug treatment advocates impressed with its ability to reverse withdrawal symptoms and craving for alcohol and various drugs of abuse. It has been used outside of the U.S. to treat addiction by American and other clinicians. But its side effects, including hallucinations, which made it popular in the 1960s drug culture, and evidence of toxicity to certain nerve cells in rodent studies have discouraged careful studies of its clinical potential against drug and alcohol addiction. The FDA has not approved use of Ibogaine in the U.S. Scientists at UCSF's Ernest Gallo Clinic and Research Center have now shown definitively in experiments with mice and rats that Ibogaine does reduce alcohol consumption, and they have determined that it does so by increasing the level of a brain protein known as glial cell line-derived neurotrophic factor, or GDNF. In a separate study, they demonstrated that GDNF by itself decreases alcohol consumption. The research is being published in the January 19 issue of The Journal of Neuroscience... ...The scientists confirmed in a cell model that Ibogaine stimulated GDNF activity. Finally, they showed that a known inhibitor of GDNF blocked Ibogaine's ability to decrease alcohol craving in the rats, suggesting a direct link between Ibogaine's desirable actions and GDNF. 'If we can alter the GDNF pathway, we may well have a new treatment against alcohol and drug addiction without the unwanted side effects of Ibogaine,' Ron said. Colleagues in the research and coauthors on the paper are postdoctoral fellows Dao-Yao He, PhD, Nancy N.H. McGough, PhHD; Ajay Ravindranathan, PhD; Jerome Jeanblanc, PhD; Marian Logrip, BA, UCSF neurology graduate student; and Khanhky Phamluong, BA, research associate, all at the Gallo Center. The research is supported by funds provided by the State of California through UCSF for medical research on alcohol and substance abuse, and by the Department of Defense. Source : University of California, San Francisco
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In the last analysis, we see only what we are ready to see, what we have been taught to see. We eliminate and ignore everything that is not a part of our prejudices. ~ Jean-Martin Charcot The future is already here — it's just not very evenly distributed. William Gibson |
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