Safety and efficacy of recombinant human platelet derived growth factor (Rhpdgf) in Parkinson's disease

Paul, Gesine; Zachrisson, Olof; Varrone, Andrea; Almqvist, Per; Jerling, Markus; Lindh, Gudrun; Rehncrona, Stig; Linderoth, Bengt; Bjartmarz, Hjálmar; Svensson, Mattias; Mercer, Katarina Jansson; Forsberg, Anna; Shafer, Lisa; Lang, Ann Marie Janson; Halldin, C.; Svenningsson, Per; Widner, Håkan; Frisén, Jonas; Pålhagen, Sven; Hægerstrand, Anders

doi:10.1016/j.jns.2013.07.457

Cited by 2 publications

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“…PDGF-BB-induced behavioural recovery was associated with a significant increase in striatal TH + fibre density and a partial restoration of TH + cell numbers in the SN, 8 weeks after the end of treatment, confirming previous findings in other rodent PD models (Zachrisson et al, 2011) and in non-human primates (Paul et al, 2013). This partial restoration was sufficient to elicit a complete behavioural recovery after PDGF-BB treatment.…”

Section: Discussionsupporting

confidence: 88%

Platelet-derived growth factor-BB has neurorestorative effects and modulates the pericyte response in a partial 6-hydroxydopamine lesion mouse model of Parkinson's disease

Padel

Özen

Boix

et al. 2016

Neurobiology of Disease

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Parkinson's disease (PD) is a neurodegenerative disease where the degeneration of the nigrostriatal pathway leads to specific motor deficits. There is an unmet medical need for regenerative treatments that stop or reverse disease progression. Several growth factors have been investigated in clinical trials to restore the dopaminergic nigrostriatal pathway damaged in PD. Platelet-derived growth factor-BB (PDGF-BB), a molecule that recruits pericytes to stabilize microvessels, was recently investigated in a phase-1 clinical trial, showing a dose-dependent increase in dopamine transporter binding in the putamen of PD patients. Interestingly, evidence is accumulating that PD is paralleled by microvascular changes, however, whether PDGF-BB modifies pericytes in PD is not known. Using a pericyte reporter mouse strain, we investigate the functional and restorative effect of PDGF-BB in a partial 6-hydroxydopamine medial forebrain bundle lesion mouse model of PD, and whether this restorative effect is accompanied by changes in pericyte features. We demonstrate that a 2-week treatment with PDGF-BB leads to behavioural recovery using several behavioural tests, and partially restores the nigrostriatal pathway. Interestingly, we find that pericytes are activated in the striatum of PD lesioned mice and that these changes are reversed by PDGF-BB treatment. The modulation of brain pericytes may contribute to the PDGF-BB-induced neurorestorative effects, PDGF-BB allowing for vascular stabilization in PD. Pericytes might be a new cell target of interest for future regenerative therapies.

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Section: Discussionsupporting

confidence: 88%

Platelet-derived growth factor-BB has neurorestorative effects and modulates the pericyte response in a partial 6-hydroxydopamine lesion mouse model of Parkinson's disease

Padel

Özen

Boix

et al. 2016

Neurobiology of Disease

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“…Studies using preclinical toxin‐induced PD models (partial 6‐OHDA model in rats, MPTP model in mice and in nonhuman primates) provided compelling evidence that intracerebroventricular (ICV) infusion of PDGF‐BB for 2 weeks restored not only DA neurotransmission, but also provided functional recovery. In PD models, injection of PDGF‐BB in lesioned animals results in increased periventricular cell proliferation, increased number of nigral tyrosine hydroxylase‐positive (TH) neurons, partial restoration of DA transporter (DAT) levels and normalization of behavioral deficits in rodents (Padel et al., ; Zachrisson et al., ) and in a nonhuman primate model (Paul et al., 2013).…”

Section: Trophic Factors In Preclinical Models Of Parkinson's Diseasementioning

confidence: 99%

Trophic factors for Parkinson's disease: Where are we and where do we go from here?

Paul

Sullivan

2018

Eur J of Neuroscience

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Perhaps the most important unmet clinical need in Parkinson's disease (PD) is the development of a therapy that can slow or halt disease progression. Extensive preclinical research has provided evidence for the neurorestorative properties of several growth factors, yet only a few have been evaluated in clinical studies. Attempts to achieve neuroprotection by addressing cell-autonomous mechanisms and targeting dopaminergic neurons have been disappointing. Four different trophic factors have so far entered clinical trials in PD: glial cell line-derived growth factor, its close structural and functional analog neurturin, platelet-derived growth factor and cerebral dopaminergic neurotrophic factor. This article reviews the pre-clinical evidence for the neuroprotective and neurorestorative actions of these growth factors and discusses limitations of preclinical models, which may hamper successful translation to the clinic. We summarize the previous and ongoing clinical trials using growth factors in PD and emphasize the caveats in clinical trial design that may prevent the further development and registration of potentially neuroprotective and neurorestorative treatments for individuals suffering from PD.

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Safety and efficacy of recombinant human platelet derived growth factor (Rhpdgf) in Parkinson's disease

Cited by 2 publications

References 0 publications

Platelet-derived growth factor-BB has neurorestorative effects and modulates the pericyte response in a partial 6-hydroxydopamine lesion mouse model of Parkinson's disease

Platelet-derived growth factor-BB has neurorestorative effects and modulates the pericyte response in a partial 6-hydroxydopamine lesion mouse model of Parkinson's disease

Trophic factors for Parkinson's disease: Where are we and where do we go from here?

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