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A number of compounds were identified as candidates for further study by the Committee to Identify Neuroprotective Agents in Parkinson's (CINAPS). Of these compounds, Minocycline, Creatine , CoQ10 and GPI 1485 have been selected for testing in the Neuroprotection Clinical Trial.

Erythropoietin

Erythropoietin (EPO) is a naturally occurring hormone that stimulates the formation of red blood cells in response to various stimuli. It has been shown to be neuroprotective in several models of central nervous system (CNS) ischemia but the mechanism is unclear. Commonly used in patients with anemia up to 1500 U/kg has been administered 3 times weekly for 3-4 weeks without any direct toxicity of the drug.

Scientific Rationale

E rythropoietin (EPO) is a naturally occurring hormone that stimulates erythropoiesis in response to various stimuli. It has been shown to be neuroprotective in several models of CNS ischemia (e.g. kainate toxicity, encephalitis, trauma and MPTP), but the mechanism is unclear.^1,2 Suggested mechanisms include antiapoptotic, anti-inflammatory, antiexcitatory, and neurotrophic activity. ^1,2

1. Brines, PNAS 2000; 97:10526-10531
2. Genc, Neurosci Lett 2001;298:139-141

Animal Model Data

RODENT: C57/BL mice were given MPTP 40 mg/kg x 2 Intraperitoneally(IP) 16 h apart while control animals received saline. One group of animals additionally received EPO 16 units, injected stereotactically above the Substantia Nigra, either after the last MPTP dose or 24 h before MPTP dose. Animals were sacrificed 7 days after the last MPTP dose. MPTP caused a 50% reduction in TH positive DA neurons which was blocked by both strategies of EPO administration. EPO also had a positive effect of several measures of locomotor activity. EPO has also been shown to increase SN and striatal nitrate concentrations.

1. Genc, Neurosci Lett 2001;298:139-141

Pharmacokinetics (including blood brain barrier (BBB) penetration)

A lthough most of the early studies of EPO in brain injury involved direct injection into the brain, EPO has been shown to cross the BBB, probably through a receptor mediated, saturable process.¹ When a 5000 U/kg dose was given IP to rats, EPO concentrations in the CSF increased by 100 mU/mL at 30 minutes. In the same study, 5000 U/kg EPO IP was shown to protect against injury from focal ischemia, trauma, inflammation and seizures. However, the results of ischemic or traumatic models may overestimate BBB penetration and may not be applicable to PD.

NOTE: Neuroprotective dosages are much higher than those required for erythropoiesis (typically 50 -300 U/kg 3 x weekly)

1. Brines, PNAS 2000; 97:10526-10531

Safety/Tolerability in Humans

• Commonly used in patients with anemia due to ESRD, malignancy, surgery or zidovudine.
• Can cause polycythemia, hypertension and seizures.
• Up to 1500 U/kg have been administered 3 x weekly for 3-4 weeks without any direct toxicity of the drug.
• Safety when administered to those without anemia is unclear.

MD Consult, 2002

Drug Interaction Potential

None observed in clinical trials

Clinical Trial/Epidemiological Evidence in Human PD

NONE

Last updated February 09, 2005