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Intranasal GDNF for Parkinson's Disease: Next steps in preclinical development
Author(s) -
Lee Waszczak Barbara,
Wachtman Lynn,
Newsome Ginnifer C,
Aly Amirah,
Silva Nilsa,
Westmoreland Susan,
Rowlett James,
Migliore Mattia M
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1177.10
Subject(s) - glial cell line derived neurotrophic factor , mptp , tyrosine hydroxylase , substantia nigra , medicine , dopamine , parkinson's disease , neurotrophic factors , saline , striatum , pharmacology , disease , dopaminergic , receptor
We have shown that glial cell line‐derived neurotrophic factor (GDNF) given by the nasal route of administration provides significant protection of substantia nigra (SN) dopamine neurons in the rat 6‐hydroxydopmaine model of Parkinson's Disease (PD). The next step in preclinical development is to test the efficacy of intranasal GDNF in a primate model of PD. Eighteen common marmosets (Callithrix jacchus) were given three doses of MPTP (2 mg/kg on day 1 and 1 mg/kg on days 2 and 3) to induce a partial lesion of the SN dopamine neurons. Nine animals received 5 daily doses of intranasal GDNF (100 μg in 50 μl saline) and nine received an equivalent volume of saline. Doses were administered on consecutive days with the first given 1 day prior to the start of MPTP, the next three doses given 1 hr prior to each dose of MPTP, and the last dose given 1 day after the last dose of MPTP. Animals recovered for 2 months before sacrifice. Lesions severity was assessed using locomotor activity monitoring, performance on an object retrieval task, motor disability scoring, and by tyrosine hydroxylase (TH) immunohistochemistry (IH) of the SN and striata of each animal. The study concluded in October 2012, and analyses of the behavioral and TH‐IH data were ongoing at the time of abstract submission. Final results will be presented.