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Neuroprotective Factor
Summary:
Neuroprotection refers to the slowing down or cessation of the loss of
brain and nervous tissue by medication or treatment. Over 300 products have
been examined for their neuroprotective effectiveness. These agents
incorporate neuroprotective factors including neurotrophins (NGF, BDNF,
NT-3, and NT-4/5) and growth factors (bFGF, IGF-1, GDNF).
A chemical reaction called oxidation, where electrons are transferred
between molecules, may be the cause of and aid the progression of Parkinson
Disease. This process causes the creation of free-radicals which can react
with lipids in the brain causing cell damage. The brain is highly
susceptible to oxidation due to its large oxygen consumption and is ideal an
ideal source for the collection of alpha-synuclein, another potential cause
for neuron degeneration. Antioxidants inhibit the production of free
radicals in the brain, acting as a neuroprotective agent. Selegiline,
Rasagiline, Requip and Mirapex are examples of antioxidants currently used
or being considered for use in the treatment of Parkinson Disease.
The NINDS Committee to Identify Neuroprotective Agents in Parkinson's (CINAPS)
selected Minocycline, Creatine , CoQ10 and GPI 1485 (no documentation
available) for evaluation in neuroprotection clinical trials.
Co-Q10, a popular 'health supplement', is a mitochondrial enzyme and an
essential component of Complex 1 and II in humans, acting as an electron
acceptor and antioxidant. It is well tolerated with minimal side effects.
Co-Q10 levels in the Substantia Nigra in PD patients are significantly
reduced. Treatment with Co-Q10 did show elevated levels in plasma, but there
were no significant evidence of change in UPDRS for dosages 800mg.
Creatine, an indirect antioxidant, has the ability to restore and maintain
cellular energy reserves. Though well tolerated, it does have side effects
including weight gain, edema, nausea, vomiting and diarrhea and, in rare
cases, muscle cramps, liver and kidney problems.
Minocycline, an antibiotic, may prevent programmed cell death (apoptosis),
exhibiting properties that may provide a neuroprotective effect. The most
common side effects include anorexia, nausea and vomiting, dizziness, rash,
hypersensitivity reactions and headache. In rare cases, liver failure,
intracranial hypertension, and black thyroid syndrome have been reported.
Potential benefits:
- Slowed or arrested progression of Parkinson Disease
- No drug interaction with traditional medication
- Dosage reduction of traditional medication providing longer
therapeutic benefits
- Reduction or cessation of medication-induced side effects such as
dyskinesia
Risks:
- Weight gain
- Short term effectiveness
- Kidney and Liver dysfunction
- Nausea and vomiting
Obstacles:
- Previously overlooked area of research related to Parkinson
Disease
- Large selection of candidate compounds with only a small
number showing enough promise for evaluation
- Outcome measures are not sufficient to allow regulatory
agencies to approve a new drug for marketing
Current research:
NIH Neuroprotective Trials (NINDS-NET PD)
- CoenzymeQ10 - dietary supplement
- Creatine - dietary supplement
- GPI 1485
- Minocycline
[1]
Neuroprotective Signal Transduction; Mattson, Mark P. (National
Institute on Aging, Baltimore, MD)
[2]
Neuroprotective agents for clinical trials in Parkinson's disease: a
systematic assessment; Ravina BM, Fagan SC, Hart RG, Hovinga CA, Murphy
DD, Dawson TM, Marler JR. (National Institute of Neurological Disorders and
Stroke, National Institutes of Health, Rockville, MD 20892-9257, USA)
[3]
Neuroprotection in Parkinson's disease: clinical trials;
Stocchi F, Olanow CW. (Department of Neuroscience and Neuromed, University
La Sapienza, Rome, Italy)
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