Restorative effects of platelet derived growth factor-BB in rodent models of Parkinson's disease.
Parkinson's disease is characterized by motor deficits caused by loss of midbrain dopaminergic neurons. Neurotrophic factors and cell transplantation have partially restored function in models of Parkinson's disease, but have had limited effects in humans. Here we show that intracerebroventricular administration of platelet-derived growth factor-BB can offer an alternative strategy to restore function in Parkinson's disease; In animal models of nigrostriatal injury, a two weeks treatment with platelet-derived growth factor-BB resulted in long-lasting restoration of striatal dopamine transporter binding sites and expression of nigral tyrosine hydroxylase. It also normalized amphetamine-induced rotational behavior in 6-hydroxydopamine lesioned rats. Platelet-derived growth factor-BB promoted proliferation of neural progenitor cells in the subventricular zone. The effects on dopaminergic neurons and functional recovery could be blocked by co-infusion with a proliferation inhibitor, indicating a link between the proliferative and anti-parkinsonian effects. Based on the current data, we consider platelet-derived growth factor-BB a clinical candidate drug for treatment of Parkinson's disease.
NeuroNova AB, Fiskartorpsvägen 15, Stockholm, Sweden.
Olof
O
Zachrisson
Ming
M
Zhao
Annica
A
Andersson
Karin
K
Dannaeus
Johan
J
Häggblad
Ruben
R
Isacson
Elisabet
E
Nielsen
Cesare
C
Patrone
Harriet
H
Rönnholm
Lilian
L
Wikstrom
Kristofer
K
Delfani
Alison L
AL
McCormack
Theo
T
Palmer
Donato A
DA
Di Monte
Michael P
MP
Hill
Ann Marie
AM
Janson Lang
Anders
A
Haegerstrand
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D043925:Angiogenesis Inducing Agents / Q000627:therapeutic use*; D000818:Animals; D000077214:Becaplermin; D049109:Cell Proliferation / Q000187:drug effects; D003561:Cytarabine / Q000627:therapeutic use; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009498:Neurotoxins / Q000633:toxicity; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D020574:Proto-Oncogene Proteins c-sis / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D043925:Angiogenesis Inducing Agents; D007166:Immunosuppressive Agents; D009498:Neurotoxins; D020574:Proto-Oncogene Proteins c-sis; D003561:Cytarabine; D000077214:Becaplermin; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine