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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)

 


Copyrightę 2012 Pipeline Project

All rights reserved. Revised: 01/26/12.