[olsen]

New :
http://www.accessphysiotherapy.com/s...searchSource=1
Each time I read about GDNF and the BBB problems, I am reminded of the following compound and wonder WHY no one has looked at it for PD. One answer I received is that the drug induces hallucinations for the initial 24 hr period after it is given. Oh yeah--ignore that sinemet does the same though having to take it daily means the hallucinations are spread out over a much longer period of time. Have attempted to find the researcher/author, but have failed to do so. Madelyn
Former posting:
(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.

[paula_w]

i don't understand the chemistry but doctors, again don't get it i agree madeline. i was psychotic probably due to having every drug in the book and anesthesia two nights in a row. if ibogaine is going to be like an acid trip. i'd risk it to be free. we are all drug addicts or will be with pd .

gdnf alone doesn't seem like enough - but there i go thinking it could happen in my lifetime again.

[olsen]

Hi Paula, posted this 4/11.
researcher on BMAA also primary researcher on Ibogaine
In the Discover article, Dr. Deborah Mash, professor at Univ of Miami Med School, is identified as a researcher into the possibility that BMAA causes neurodegenerative diseases. She is also a primary researcher on "Ibogaine" an orally administered substance used to increase GDNF and treat addictions; seems the oral form crosses the BBB.
from former posting on Ibogaine:
"...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..."

http://neurotalk.psychcentral.com/sh...ional+medicine

The use of Ibogaine is currently in clinical trials for the treatment of addictions, esp alcoholism.Seems a major problem with studying this drug is that it is a naturally occurring plant product and thus not patentable. hopefuly some pharma co will become interested and extract the active substrate and synthesize it. thus making it patentable. Dr. Mash maintains she has developed a patented compound which does not cause hallucinations. who knows......

[trixiedee]

Wow - Ibogaine is like the strongest acid trip imaginable, it is used shamanically in Africa but you would need supervision as it lasts about 30 hours and you are in a different world while on it. It is an amazing herb, I have read a book about it called 'Breaking Open the Head' by Daniel Pinchbeck. Anecdotal stories about it curing addiction are very impressive. I can't imagine it ever being legal though as it is such a powerful psychedelic. LSD was my drug of choice for a few years in my 20s, I would be interested in trying Ibogaine (or ayahuasca, which also is meant to be beneficial for PD) but I'd be a bit scared as I'm not as courageous a pychonaut as I was when I was healthy

Trixiedee