Intranasal gene delivery for treating Parkinson’s disease: overcoming the blood–brain barrier

Abstract

A number of genes encoding neurotrophic factors have therapeutic potential for PD, but few have been tested by the intranasal route and shown to be neuroprotective in a model of PD. Intranasal delivery provides a largely unexplored, promising approach for development of a non-invasive gene therapy for PD.

Synthetic Peptides Affect the Expression of <i>Gdnf</i> and Gdnf Receptors in Rats with 6-OHDA-Induced PD-Like Parkinsonism

“…Our data are consistent with their results, despite the fact that we used course intranasal administration of the peptide instead of direct infusion into the brain. Our findings confirm that intranasal administration of the peptides can affect processes occurring in the brain [20].…”

“…GDNF demonstrates robust restorative and protective effects on DA neurons [11]- [14]. However, the clinical utility of GDNF has been compromised by a failed phase II trial, potential toxicity [15], limited diffusion of GDNF to target areas [16] [17], and difficult delivery [18] [19], which may be overcome by a promising approach of intranasal delivery [20].…”

Gene formulations, gene prescriptions

“…Podkreśla się użyteczność terapeutyczną opracowywania np. donosowych / inhalacyjnych leków genowych [16,17]. Poprawność koncepcyjną zamysłu uzyskiwania nowych formulacji genowych zawsze weryfikują badania podstawowe.…”

intranasal GDNF gene therapy approach for treating Parkinson's disease

“…Importantly, many of the trophic factors which enter and exert biological effects in the brain after nasal delivery also have neuroprotective and neuroregenerative potential toward SN dopamine neurons and could potentially be developed as treatments for PD. The most promising and widely cited examples of therapeutic biomolecules shown to reach the brain after intranasal administration have been summarized in our review article 100 and are listed on the right side in the Venn diagram ( Figure 7) and recapitulated below. However, except for GDNF 101 , bFGF 92 , and insulin 102 , none have been tested by the intranasal route in a Parkinson's disease model.…”

“…Although many of these agents do reach the brain after intranasal administration (Table 3), none were evaluated by this route in a model of PD, with the exception of insulin 102 , FGF 92 , GDNF 101 and pGDNF_1b NPs 100,160,164 . In addition to those listed in Table 3 …”