Reflection and ReactionContinuing trials of GDNF in Parkinson's disease
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Cited by (49)
Restorative cell and gene therapies for Parkinson's disease
2023, Handbook of Clinical NeurologyNeuroprotective effects of a brain permeant 6-aminoquinoxaline derivative in cell culture conditions that model the loss of dopaminergic neurons in Parkinson disease
2015, European Journal of Medicinal ChemistryCitation Excerpt :Those treatments should be, however, given as early as possible to be effective in PD patients, as motor symptoms appear when the depopulation in DA cell bodies exceeds 50% [5]. Glial-cell derived neurotrophic factor (GDNF) has been proposed as a therapeutic agent to delay the development of PD [6], but clinical trials have been disappointing, probably due to inherent drawbacks associated with the use of peptides applied as drugs, including pleiotropic effects, short half-life and inability to cross the blood–brain barrier (BBB), thus imposing repeated transcranial injections, with undesirable side-effects [7,8]. Substantial efforts have been made, therefore, to develop non-peptidic small molecules with protective/restorative activities for DA neurons [9].
Clinical applications involving CNS gene transfer
2014, Advances in GeneticsCitation Excerpt :A potential caveat of this approach is that high levels of GDNF may trigger serious side effects arising from the overexpression of dopamine neurotransmitter in inappropriate cells, tyrosine hydroxylase silencing, and alteration of the dopamine levels in the striatum, all demonstrated in rodents (Ferreira et al., 2007; Shoulson, 1998; Simola, Morelli, & Pinna, 2008). Conversely, low levels of expression of the GDNF could be insufficient for achieving therapeutic effects, as evidenced in clinical trials-delivered GDNF by means of intraputaminal injections (Barker, 2006; Evans & Barker, 2008; Nutt et al., 2003). In addition, more work should be done to ensure safety of the therapy, if the GDNF is pursued as a target (Yu & Neimat, 2008).
Neurotrophic factors for the treatment of Parkinson's disease
2011, Cytokine and Growth Factor ReviewsRepairing the parkinsonian brain with neurotrophic factors
2011, Trends in NeurosciencesCitation Excerpt :Several possible explanations for the different outcomes in these trials have been proposed, including differences in GDNF doses or catheter properties, the choice of patient cohorts or the selection of inappropriate endpoints. A major limiting factor in the abovementioned trials was suggested to be the suboptimal brain delivery of GDNF [27,45,46]. The experimental and clinical evidence obtained so far with NTFs suggests that sustained and localized NTF delivery is crucial for producing beneficial results.