GDNF AND PARKINSON'S DISEASE -
SAFETY, EFFECTS AND RISKS
SAFETY, EFFECTS AND RISKS
A human therapeutic trial using intraputaminal infusion of glial cell-derived
neurotrophic factor (GDNF) in Parkinson's disease was abruptly terminated, partly
due to safety concerns raised by the finding of cerebellar lesions in monkeys given
high-dose GDNF. [P1]
Potential future treatments for Parkinson's disease should include those that not only
provide symptomatic relief to patients but also neuroprotective and/or
neurorestorative. Low dopaminergic cell survival and suboptimal fiber reinnervation
are likely major contributing factors for the limited benefits of neural transplantation in
Parkinson's disease (PD) patients. [1]
Glial cell lined-derived neurotrophic factor (GDNF) has been shown to enhance
dopaminergic cell survival and fiber outgrowth of the graft site as well as promote
behavioral recovery in rodent models of Parkinson's disease. [1,2] Positive results
using monkeys have encouraged the use of GDNF in human trials. [P3]
Shortage of dopamine causes Parkinson's disease leading to problems in
movement, mood and behavior. GDNF seems to be able to stimulate dopamine
production and prevent neuron degeneration. Three years ago, a group of
Parkinson's patients had been treated with GDNF (glial derived neurotrophic growth
factor) at Bristol's Frenchay Hospital and they were suddenly able to walk, talk and
smile again. [3]
Unfortunately studies have shown mixed results, illustrating the influence that various
parameters of administration can have on clinical outcome. [P3]
Bolus intraventricular injections of GDNF in primates have shown some behavioural
efficacy, there was no clinical benefit in the first human trial using this method, which
was most likely a result of inefficient GDNF distribution in the striatal parenchyma. In
primates, however, continuous (rather than bolus) delivery of GDNF into the ventricles
results in significant distribution in the striatum. While chronic delivery of GDNF into
the ventricles has not been assessed in humans. [P3]
Intraputamenal protein delivery in two Phase I trials have demonstrated that GDNF
considerably reduces Parkinson's disease symptoms, suggesting that the putamen is
the optimal location for delivery.
However, researchers from Michael J. Fox Foundation for Parkinson's Research,
New York, pointed out that results from a recent controlled clinical study delivering the
neurotrophic factor, glial-derived neurotrophic factor (GDNF), directly into brain did
not demonstrate efficacy and safety of such a treatment. [P2]
However, the possibility of high levels of GDNF resulting in widespread distribution of
GDNF to non-targeted areas is a cause of concern. [P3] Consequently, Amgen, the
innovator company, stopped the manufacturing GDNF and claimed that the drug
could cause a serious side effect - brain damage. In a U.S study, researchers found
antibodies in the brain of one or two patients. While in an animal study, high doses of
GDNF caused irreversible brain damage, and subsequently death. [3, P1]
Is there any evidence about the side effects of GDNF in human?
Researchers at University of Kentucky studied the magnetic resonance images of the
cerebellum or elsewhere from nine Parkinson's disease patients participating in a
trial. They compared these images with image from 25 normal adults, images taken
between pre and post-GDNF infusion scans using a repeated measures. They found
no significant cerebellar differences in any of the nine individual Parkinson's disease
patients, no significant morphometric differences between pre- and post-GDNF
scans and no signal abnormalities in the cerebellum detected on the FLAIR images in
Parkinson's disease patients. Basically, they found no imaging evidence of cerebellar
injury in human subjects undergoing chronic intracerebral GDNF infusion. [P1]
Though the results of findings are exciting, we still do not know the long-term effects.
Researchers suggest the need of vectors. Vector mediated delivery of GDNF may
provide a suitable means for long-term intraputamenal delivery. The development of
these vectors should be the way forward for GDNF treatment. [P3]
ALL RIGHTS RESERVED ZHION. THIS ARTICLE IS NOT A MEDICAL ADVICE. CONSULT WITH YOUR DOCTOR FOR ANY
QUESTIONS.
[1] McLeod M, et al, Erythropoietin and GDNF enhance ventral mesencephalic fiber outgrowth and capillary proliferation
following neural transplantation in a rodent model of Parkinson's disease. Eur J Neurosci. 2006 Jul;24(2):361-70. [2] Dietz
GP, et al, Application of a blood-brain-barrier-penetrating form of GDNF in a mouse model for Parkinson's disease. Brain Res.
2006 Apr 12;1082(1):61-6. [3] Why won't they let Parkinson's sufferers take a life-changing drug? NIKKI MURFITT Daily Mail
31st October 2006 [P1] Chebrolu H, et al, MRI volumetric and intensity analysis of the cerebellum in Parkinson's disease
patients infused with glial-derived neurotrophic factor (GDNF). Exp Neurol. 2006 Apr;198(2):450-6. Epub 2006 Feb 7. [P2]
Sherer TB, et al, Crossroads in GDNF therapy for Parkinson's disease. Mov Disord. 2006 Feb;21(2):136-41. [P3] Eslamboli A.
Assessment of GDNF in primate models of Parkinson's disease: comparison with human studies. Rev Neurosci.
2005;16(4):303-10.
neurotrophic factor (GDNF) in Parkinson's disease was abruptly terminated, partly
due to safety concerns raised by the finding of cerebellar lesions in monkeys given
high-dose GDNF. [P1]
Potential future treatments for Parkinson's disease should include those that not only
provide symptomatic relief to patients but also neuroprotective and/or
neurorestorative. Low dopaminergic cell survival and suboptimal fiber reinnervation
are likely major contributing factors for the limited benefits of neural transplantation in
Parkinson's disease (PD) patients. [1]
Glial cell lined-derived neurotrophic factor (GDNF) has been shown to enhance
dopaminergic cell survival and fiber outgrowth of the graft site as well as promote
behavioral recovery in rodent models of Parkinson's disease. [1,2] Positive results
using monkeys have encouraged the use of GDNF in human trials. [P3]
Shortage of dopamine causes Parkinson's disease leading to problems in
movement, mood and behavior. GDNF seems to be able to stimulate dopamine
production and prevent neuron degeneration. Three years ago, a group of
Parkinson's patients had been treated with GDNF (glial derived neurotrophic growth
factor) at Bristol's Frenchay Hospital and they were suddenly able to walk, talk and
smile again. [3]
Unfortunately studies have shown mixed results, illustrating the influence that various
parameters of administration can have on clinical outcome. [P3]
Bolus intraventricular injections of GDNF in primates have shown some behavioural
efficacy, there was no clinical benefit in the first human trial using this method, which
was most likely a result of inefficient GDNF distribution in the striatal parenchyma. In
primates, however, continuous (rather than bolus) delivery of GDNF into the ventricles
results in significant distribution in the striatum. While chronic delivery of GDNF into
the ventricles has not been assessed in humans. [P3]
Intraputamenal protein delivery in two Phase I trials have demonstrated that GDNF
considerably reduces Parkinson's disease symptoms, suggesting that the putamen is
the optimal location for delivery.
However, researchers from Michael J. Fox Foundation for Parkinson's Research,
New York, pointed out that results from a recent controlled clinical study delivering the
neurotrophic factor, glial-derived neurotrophic factor (GDNF), directly into brain did
not demonstrate efficacy and safety of such a treatment. [P2]
However, the possibility of high levels of GDNF resulting in widespread distribution of
GDNF to non-targeted areas is a cause of concern. [P3] Consequently, Amgen, the
innovator company, stopped the manufacturing GDNF and claimed that the drug
could cause a serious side effect - brain damage. In a U.S study, researchers found
antibodies in the brain of one or two patients. While in an animal study, high doses of
GDNF caused irreversible brain damage, and subsequently death. [3, P1]
Is there any evidence about the side effects of GDNF in human?
Researchers at University of Kentucky studied the magnetic resonance images of the
cerebellum or elsewhere from nine Parkinson's disease patients participating in a
trial. They compared these images with image from 25 normal adults, images taken
between pre and post-GDNF infusion scans using a repeated measures. They found
no significant cerebellar differences in any of the nine individual Parkinson's disease
patients, no significant morphometric differences between pre- and post-GDNF
scans and no signal abnormalities in the cerebellum detected on the FLAIR images in
Parkinson's disease patients. Basically, they found no imaging evidence of cerebellar
injury in human subjects undergoing chronic intracerebral GDNF infusion. [P1]
Though the results of findings are exciting, we still do not know the long-term effects.
Researchers suggest the need of vectors. Vector mediated delivery of GDNF may
provide a suitable means for long-term intraputamenal delivery. The development of
these vectors should be the way forward for GDNF treatment. [P3]
ALL RIGHTS RESERVED ZHION. THIS ARTICLE IS NOT A MEDICAL ADVICE. CONSULT WITH YOUR DOCTOR FOR ANY
QUESTIONS.
[1] McLeod M, et al, Erythropoietin and GDNF enhance ventral mesencephalic fiber outgrowth and capillary proliferation
following neural transplantation in a rodent model of Parkinson's disease. Eur J Neurosci. 2006 Jul;24(2):361-70. [2] Dietz
GP, et al, Application of a blood-brain-barrier-penetrating form of GDNF in a mouse model for Parkinson's disease. Brain Res.
2006 Apr 12;1082(1):61-6. [3] Why won't they let Parkinson's sufferers take a life-changing drug? NIKKI MURFITT Daily Mail
31st October 2006 [P1] Chebrolu H, et al, MRI volumetric and intensity analysis of the cerebellum in Parkinson's disease
patients infused with glial-derived neurotrophic factor (GDNF). Exp Neurol. 2006 Apr;198(2):450-6. Epub 2006 Feb 7. [P2]
Sherer TB, et al, Crossroads in GDNF therapy for Parkinson's disease. Mov Disord. 2006 Feb;21(2):136-41. [P3] Eslamboli A.
Assessment of GDNF in primate models of Parkinson's disease: comparison with human studies. Rev Neurosci.
2005;16(4):303-10.
 |  |  |  |  |
THIS WEBSITE TALKS ABOUT THE SIDE EFFECTS AND THE POTENTIAL HEALTH BENEFITS OF HERBS, SUPPLEMENTS,
 | |  | |  | |  | |  | |  |