Image-guided convection-enhanced delivery of GDNF protein into monkey putamen

Gimenez, Francisco; Krauze, Michal T.; Valles, Francisco; Hadaczek, Piotr; Bringas, John; Sharma, Nitasha; Forsayeth, John; Bankiewicz, Krystof S.

doi:10.1016/j.neuroimage.2010.01.023

Cited by 51 publications

(39 citation statements)

References 28 publications

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“…Consequently, the direct delivery of GDNF to the brain was the primary focus of translational research. Delivery strategies have included the direct administration of the molecule, its encapsulation in microspheres composed of biodegradable polymers to achieve a controlled release over a prolonged period of time, DNA nanoparticle gene transfer, and convection-enhanced delivery [76][77][78][79]. Interactions of GDNF with components of the extracellular matrix ,its activation of receptors other than RET/GFRα1, induction of anti-GDNF antibodies by recombinant GDNF are all factors hampering the use of the full molecule in therapy.…”

Section: Protein Based-therapymentioning

confidence: 99%

Targeting the glial-derived neurotrophic factor and related molecules for controlling normal and pathologic pain

Merighi

2015

Expert Opinion on Therapeutic Targets

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Introduction: GDNF and its family of ligands (GFLs) have several functions in the nervous system. As a survival factor for dopaminergic neurons, GDNF was used in clinical trials for Parkinson's disease. However, GFLs their receptors are potential targets for new pain-controlling drugs. Such a potential should not be underestimated because molecules with analgesic activities in rodents mostly failed to be effective in translational studies. Areas covered:The circuitry, molecular and cellular mechanisms by which GFLs control nociception, their intervention in inflammatory and neuropathic pain, the problems related to effective GDNF delivery to the brain, the possibility to target the GFL receptor complex rather than its ligands, also by the use of non-peptidyl agonists, are discussed. Expert opinion:In nociceptive pathways, an ideal drug should either: i. Target the release of endogenous GFLs from large dense-cored vesicles (LGVs) by acting e.g. onto the phosphatidylinositol-3-phosphate [PtdIns(3)P] pool, which is sensitive to Ca 2+ modulation; ii. Target the GFL receptor complex. Besides to XIB403, a thiol molecule that enhances GFRα family receptor signaling, existing drugs such as retinoic acid and amitriptyline should be considered for effective targeting of GDNF, at least in neuropathic pain. The approach of pain modeling in experimental animals is discussed.

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Section: Protein Based-therapymentioning

confidence: 99%

Targeting the glial-derived neurotrophic factor and related molecules for controlling normal and pathologic pain

Merighi

2015

Expert Opinion on Therapeutic Targets

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“…CED has been extensively investigated in the context of a wide range of CNS disorders in both preclinical and clinical trials, most notably for the treatment of brain tumors and Parkinson's disease. [5][6][7][8][9][10][11] Drugs can be administered directly to the brain by CED in concentrations that would result in significant toxicity if given systemically. In contrast to delivery techniques that are dependent on diffusion, CED enables the controlled, homogeneous distribution of drugs through large brain volumes.…”

Section: Introductionmentioning

confidence: 99%

Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model

Singleton¹,

Collins²,

Bienemann³

et al. 2017

IJN

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Background The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood–brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED). Materials and methods The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay. Nano-micelle distribution in rat brain was analyzed following acute CED using rhodamine-labeled nano-micelles, and toxicity was assayed using immunofluorescent microscopy and synaptophysin enzyme-linked immunosorbent assay. We compared the survival of the bioluminescent syngenic F98/Fischer344 rat glioblastoma model treated by acute CED of panobinostat-loaded nano-micelles with that of untreated and vehicle-only-treated controls. Results Nano-micellar panobinostat is cytotoxic to rat and human glioma cells in vitro in a dose-dependent manner following short-time exposure to drug. Fluorescent rhodamine-labelled nano-micelles distribute with a volume of infusion/volume of distribution (Vi/Vd) ratio of four and five respectively after administration by CED. Administration was not associated with any toxicity when compared to controls. CED of panobinostat-loaded nano-micelles was associated with significantly improved survival when compared to controls (n=8 per group; log-rank test, P <0.001). One hundred percent of treated animals survived the 60-day experimental period and had tumour response on post-mortem histological examination. Conclusion CED of nano-micellar panobinostat represents a potential novel therapeutic option for malignant glioma and warrants translation into the clinic.

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“…Initially described by Bobo et al [1] using albumin-linked surrogate tracers [8] , our current technique of RCD employs interventional MRI (inMRI) to monitor the distribution of therapeutic agents that are coinfused with gadolinium-related tracers [9] . Our initial work with gadolinium-loaded liposomes [10,11] has progressed to the coinfusion of free gadoteridol for predicting the distribution of protein [12] and AAV2 vectors [9,11,13] . A similar strategy, coinfusion of therapeutic agents and Gd-diethylenetriamene pentaacetic acid (Gd-DTPA), has been used by Lonser et al [14] to treat patients with intrinsic brainstem lesions in clinical trials at the National Institutes of Health.…”

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confidence: 99%

Novel Platform for MRI-Guided Convection-Enhanced Delivery of Therapeutics: Preclinical Validation in Nonhuman Primate Brain

Richardson

Kells

Martin

et al. 2011

Stereotact Funct Neurosurg

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Image-guided convection-enhanced delivery of GDNF protein into monkey putamen

Cited by 51 publications

References 28 publications

Targeting the glial-derived neurotrophic factor and related molecules for controlling normal and pathologic pain

Targeting the glial-derived neurotrophic factor and related molecules for controlling normal and pathologic pain

Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model

Novel Platform for MRI-Guided Convection-Enhanced Delivery of Therapeutics: Preclinical Validation in Nonhuman Primate Brain

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