Recent Research about Treatment for Parkinson's Disease July 2013
ABOUT PARKINSON'S DISEASE
More than a million Americans suffer from Parkinson's Disease, So far, no current therapies alter the fundamental
clinical course of the condition. Parkinson's disease is related to dopamine depletion in the putamen, which leads to
motor dysfunction. As the disease progresses, a substantial degree of dopamine depletion also occurs in other brain
locations such as caudate and nucleus accumbens. This leads to psychiatric issues such as including depression,
apathy, and cognitive decline. [4]
Dopamine replacement therapy partially restores motor function but it also has side effects, such as motor fluctuations
and dyskinesias. Positron emission tomography (PET) studies suggest that the dopamine release rate is substantially
higher in Parkinson's disease subjects with motor complications compared to stable responders. This differential pattern
of dopamine release actually occurs the early stages of the disease, before motor complications are noticeable. Striatal
dopamine depletion in Parkinson's disease leads to reduced plasticity in the primary motor cortex and, presumably, in
non-motor cortical areas as well. Although dopamine replacement therapy tends to restore physiological plasticity,
treatment-induced motor, and neuropsychiatric complications could be related to abnormalities in corticostriatal synaptic
plasticity. [4]
The most common treatment for Parkinson's Disease is the oral administration of the dopamine precursor, L-dopa.
L-dopa subsides the symptoms at first, it becomes ineffective over the time. This article summarizes recent research
findings on alternative approach for treating Parkinson's Disease patients.
_____________________________________________________________________________________________
Complications, Risk Factors, Related Diseases
Deep vein thrombosis
Deep vein thrombosis was detected in 23 patients (20%) with Parkinson's disease. Deep vein thrombosis was located in
the distal portion in 18 patients and in the proximal portion in 5 patients. [8]
Gait difficulties
Gait (manner of walking) difficulties and falls are commonly reported in people with Parkinson disease. Reduction in gait
speed is a major characteristic of Parkinsonian gait. [10]
Pulmonary thromboembolism
Pulmonary thromboembolism is a common cause of death in patients with autopsy-confirmed Parkinsonism. [8]
Visual Hallucination
During a visual hallucination, a marked desynchronization occurs between posterior and anterior cortical areas involved
in visual processing in Parkinson's desease patients. [9]
_____________________________________________________________________________________________
The Treatments, The Research Findings
Amphetamine
By eliminating the dopamine transporter-the protein responsible for recycling the chemical into neurons-in mice,
dopamine levels were reduced in the midbrain by 20-fold. This inhibition of dopamine production resulted in essentially
unmeasurable levels of the neurotransmitter. Using this model, drugs related to amphetamine were found to be effective
in ameliorating muscle rigidity, tremor, and impaired movement. [1]
The most effective was methylenedioxymethamphetamine HCl (MDMA), commonly known as ecstasy. It has been shown
that amphetamines can trigger release of neurotransmitters such as dopamine, serotonin, and norepinephrine and
cause sudden bursts in neurotransmission, leading to a feeling of alertness, increased muscular activity, and reduced
fatigue. But MDMA did not raise dopamine levels, hinting that it restores movement through an unknown mechanism
outside of the dopamine system. It was also found that a combination of MDMA and the current Parkinson's drug
L-DOPA, a chemical building block of dopamine was more effective than either drug alone.[1]
Alpha-synuclein in Parkinson's symptoms
When alpha-synuclein becomes mutated and clumps at the cell surface, it manages to drag away a protein that helps
transport the ER and the Golgi Bodies. This gives a new direction for considering much better treatments, e.g. gene
therapy, for people suffered from Parkinson's Disease. {2)
Curcumin
There are increasing evidence supports the pharmaceutical potential of curcumin, a polyphenolic compound in the
spice turmeric, against Parkinson's disease. [7]
Glial cell line-derived neurotrophic factor (GDNF)
In a Parkinson's Disease vitro study, the neuroprotective mechanism of the GDNF on the 6-hydroxydopamine
(6-OHDA)-induced dopaminergic cell line MN9D damage was observed. The mechanism may be related to enhancing
the expression of the apoptosis inhibiting genes and decreasing the expression of the apoptosis promoting genes. [6]
Rivastigmine
Parkinson's disease patients with cognitive impairment show numerous regions of decreased spontaneous brain
function compared with controls, and rivastigmine is associated with performance-related normalization in the left frontal
cortex function in a study found. [5]
Subthalamic nucleus deep brain stimulation (STN-DBS)
A 6 year-study shows that a superior efficacy of nucleus deep brain stimulation (STN-DBS) on motor disability,
compared to medical treatments. However, there was no significant differences were observed in the progression of
motor symptoms and, apart from phonemic verbal fluency, of neuropsychological alterations. [3]
____________________________________________________________________________________________
Related Articles
More about Parkinson's Disease
Parkinson's Disease - Supplements
Parkinson's Disease - Herbs
Parkinson's Disease - Side Effects of Drugs
Parkinson's Disease - Symptoms
Stimulants for Growth Hormone Secretion
____________________________________________________________________________________________
References
[1] Sotnikova TD, Beaulieu JM, Barak LS, Wetsel WC, Caron MG, et al. (2005) Dopamine-independent locomotor
actions of amphetamines in a novel acute mouse model of Parkinson's disease. PLoS Biol 3(8): e271.
[2] Researchers reverse Parkinson's symptoms in animal models EurekAlet June 22 2006.
[3] Merola A, et al, Medical therapy and subthalamic deep brain stimulation in advanced Parkinson's disease: a different
long-term outcome? J Neurol Neurosurg Psychiatry. 2013 Jul 11
[4] de la Fuente-Fernández R. Imaging of Dopamine in PD and Implications for Motor and Neuropsychiatric
Manifestations of PD. Front Neurol. 2013 Jul 9;4:90. PD=Parkinson's disease.
[5] Possin KL et al, Rivastigmine is associated with restoration of left frontal brain activity in Parkinson's disease. Mov
Disord. 2013 Jul 11.
[6] Li F, et al, The Potential Neuroprotection Mechanism of GDNF in the 6-OHDA-Induced Cellular Models of Parkinson's
Disease. Cell Mol Neurobiol. 2013 Jul 12.
[7] Ji HF, et al, The Multiple Pharmaceutical Potential of Curcumin in Parkinson's Disease. CNS Neurol Disord Drug
Targets. 2013 Jul 5
[8] Yamane K, et al, Postural abnormality as a risk marker for leg deep venous thrombosis in Parkinson's disease. PLoS
One. 2013 Jul 2;8(7
[9] Goetz CG et al, I finally see what you see: Parkinson's disease visual hallucinations captured with functional
neuroimaging. Mov Disord. 2013 Jul 10. [10] Nemanich ST, et al, Predictors of gait speeds and the relationship of gait
speeds to falls in men and women with Parkinson disease. Parkinsons Dis. 2013;2013:141720
More than a million Americans suffer from Parkinson's Disease, So far, no current therapies alter the fundamental
clinical course of the condition. Parkinson's disease is related to dopamine depletion in the putamen, which leads to
motor dysfunction. As the disease progresses, a substantial degree of dopamine depletion also occurs in other brain
locations such as caudate and nucleus accumbens. This leads to psychiatric issues such as including depression,
apathy, and cognitive decline. [4]
Dopamine replacement therapy partially restores motor function but it also has side effects, such as motor fluctuations
and dyskinesias. Positron emission tomography (PET) studies suggest that the dopamine release rate is substantially
higher in Parkinson's disease subjects with motor complications compared to stable responders. This differential pattern
of dopamine release actually occurs the early stages of the disease, before motor complications are noticeable. Striatal
dopamine depletion in Parkinson's disease leads to reduced plasticity in the primary motor cortex and, presumably, in
non-motor cortical areas as well. Although dopamine replacement therapy tends to restore physiological plasticity,
treatment-induced motor, and neuropsychiatric complications could be related to abnormalities in corticostriatal synaptic
plasticity. [4]
The most common treatment for Parkinson's Disease is the oral administration of the dopamine precursor, L-dopa.
L-dopa subsides the symptoms at first, it becomes ineffective over the time. This article summarizes recent research
findings on alternative approach for treating Parkinson's Disease patients.
_____________________________________________________________________________________________
Complications, Risk Factors, Related Diseases
Deep vein thrombosis
Deep vein thrombosis was detected in 23 patients (20%) with Parkinson's disease. Deep vein thrombosis was located in
the distal portion in 18 patients and in the proximal portion in 5 patients. [8]
Gait difficulties
Gait (manner of walking) difficulties and falls are commonly reported in people with Parkinson disease. Reduction in gait
speed is a major characteristic of Parkinsonian gait. [10]
Pulmonary thromboembolism
Pulmonary thromboembolism is a common cause of death in patients with autopsy-confirmed Parkinsonism. [8]
Visual Hallucination
During a visual hallucination, a marked desynchronization occurs between posterior and anterior cortical areas involved
in visual processing in Parkinson's desease patients. [9]
_____________________________________________________________________________________________
The Treatments, The Research Findings
Amphetamine
By eliminating the dopamine transporter-the protein responsible for recycling the chemical into neurons-in mice,
dopamine levels were reduced in the midbrain by 20-fold. This inhibition of dopamine production resulted in essentially
unmeasurable levels of the neurotransmitter. Using this model, drugs related to amphetamine were found to be effective
in ameliorating muscle rigidity, tremor, and impaired movement. [1]
The most effective was methylenedioxymethamphetamine HCl (MDMA), commonly known as ecstasy. It has been shown
that amphetamines can trigger release of neurotransmitters such as dopamine, serotonin, and norepinephrine and
cause sudden bursts in neurotransmission, leading to a feeling of alertness, increased muscular activity, and reduced
fatigue. But MDMA did not raise dopamine levels, hinting that it restores movement through an unknown mechanism
outside of the dopamine system. It was also found that a combination of MDMA and the current Parkinson's drug
L-DOPA, a chemical building block of dopamine was more effective than either drug alone.[1]
Alpha-synuclein in Parkinson's symptoms
When alpha-synuclein becomes mutated and clumps at the cell surface, it manages to drag away a protein that helps
transport the ER and the Golgi Bodies. This gives a new direction for considering much better treatments, e.g. gene
therapy, for people suffered from Parkinson's Disease. {2)
Curcumin
There are increasing evidence supports the pharmaceutical potential of curcumin, a polyphenolic compound in the
spice turmeric, against Parkinson's disease. [7]
Glial cell line-derived neurotrophic factor (GDNF)
In a Parkinson's Disease vitro study, the neuroprotective mechanism of the GDNF on the 6-hydroxydopamine
(6-OHDA)-induced dopaminergic cell line MN9D damage was observed. The mechanism may be related to enhancing
the expression of the apoptosis inhibiting genes and decreasing the expression of the apoptosis promoting genes. [6]
Rivastigmine
Parkinson's disease patients with cognitive impairment show numerous regions of decreased spontaneous brain
function compared with controls, and rivastigmine is associated with performance-related normalization in the left frontal
cortex function in a study found. [5]
Subthalamic nucleus deep brain stimulation (STN-DBS)
A 6 year-study shows that a superior efficacy of nucleus deep brain stimulation (STN-DBS) on motor disability,
compared to medical treatments. However, there was no significant differences were observed in the progression of
motor symptoms and, apart from phonemic verbal fluency, of neuropsychological alterations. [3]
____________________________________________________________________________________________
Related Articles
More about Parkinson's Disease
Parkinson's Disease - Supplements
Parkinson's Disease - Herbs
Parkinson's Disease - Side Effects of Drugs
Parkinson's Disease - Symptoms
Stimulants for Growth Hormone Secretion
____________________________________________________________________________________________
References
[1] Sotnikova TD, Beaulieu JM, Barak LS, Wetsel WC, Caron MG, et al. (2005) Dopamine-independent locomotor
actions of amphetamines in a novel acute mouse model of Parkinson's disease. PLoS Biol 3(8): e271.
[2] Researchers reverse Parkinson's symptoms in animal models EurekAlet June 22 2006.
[3] Merola A, et al, Medical therapy and subthalamic deep brain stimulation in advanced Parkinson's disease: a different
long-term outcome? J Neurol Neurosurg Psychiatry. 2013 Jul 11
[4] de la Fuente-Fernández R. Imaging of Dopamine in PD and Implications for Motor and Neuropsychiatric
Manifestations of PD. Front Neurol. 2013 Jul 9;4:90. PD=Parkinson's disease.
[5] Possin KL et al, Rivastigmine is associated with restoration of left frontal brain activity in Parkinson's disease. Mov
Disord. 2013 Jul 11.
[6] Li F, et al, The Potential Neuroprotection Mechanism of GDNF in the 6-OHDA-Induced Cellular Models of Parkinson's
Disease. Cell Mol Neurobiol. 2013 Jul 12.
[7] Ji HF, et al, The Multiple Pharmaceutical Potential of Curcumin in Parkinson's Disease. CNS Neurol Disord Drug
Targets. 2013 Jul 5
[8] Yamane K, et al, Postural abnormality as a risk marker for leg deep venous thrombosis in Parkinson's disease. PLoS
One. 2013 Jul 2;8(7
[9] Goetz CG et al, I finally see what you see: Parkinson's disease visual hallucinations captured with functional
neuroimaging. Mov Disord. 2013 Jul 10. [10] Nemanich ST, et al, Predictors of gait speeds and the relationship of gait
speeds to falls in men and women with Parkinson disease. Parkinsons Dis. 2013;2013:141720
 |  |  |  |  |
 | |  |