NeuroNova AB, Fiskartorpsvägen 15, Stockholm, Sweden.
J Parkinsons Dis. 2011;1(1):49-63. doi: 10.3233/JPD-2011-0003.
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.
帕金森病的特征是中脑多巴胺能神经元丧失导致的运动功能障碍。神经营养因子和细胞移植已部分恢复了帕金森病模型中的功能，但对人类的效果有限。在这里，我们展示了脑室内给予血小板衍生生长因子-BB 可以提供一种替代策略来恢复帕金森病的功能；在黑质纹状体损伤的动物模型中，血小板衍生生长因子-BB 治疗两周可导致纹状体多巴胺转运体结合位点和黑质酪氨酸羟化酶表达的持久恢复。它还使 6-羟多巴胺损伤大鼠的安非他命诱导的旋转行为正常化。血小板衍生生长因子-BB 促进侧脑室下区神经祖细胞的增殖。与增殖抑制剂共输注可阻断对多巴胺能神经元和功能恢复的影响，表明增殖和抗帕金森作用之间存在联系。基于目前的数据，我们认为血小板衍生生长因子-BB 是治疗帕金森病的临床候选药物。
