Interestingly, it appears that the NTN mutation reported here is not sufficient to cause HSCR, and this multiplex family also segregates a RET mutation.
Relationship between the type of RET/GDNF/NTN or SOX10 gene mutations and long-term results after surgery for total colonic aganglionosis with small bowel involvement.
Here, we show that PCC produce the neurotrophic factor NRTN, which reinforces their biological properties, triggers neuroplastic alterations, NI and influences pain sensation via the GFRα-2 receptor.
In summary, we report for the first time the association of PSPN gene with HSCR and confirm the involvement of NRTN in the disease, with the identification of novel variants in those genes.
Germline mutations of the RET proto-oncogene (RET), its ligand glial cell-derived neurotrophic factor (GDNF), and neurturin (NTN) gene have been reported in patients with Hirschsprung's disease.
Although mutations in eight different genes (EDNRB, EDN3, ECE1, SOX10, RET, GDNF, NTN, SIP1) have been identified in affected individuals, it is now clear that RET and EDNRB are the primary genes implicated in the etiology of HSCR.
Three gene transfer paradigms for Parkinson's disease have been explored: converting L-dopa into dopamine through AADC gene delivery in the putamen; synthesizing GABA through GAD gene delivery in the overactive subthalamic nucleus and providing neurotrophic support through neurturin gene delivery in the nigro-striatal pathway.
Gene therapy has emerged as a potential breakthrough in the treatment of PD and early clinical trials using AAV2-neurturin, a trophic factor that has shown the ability to protect dopaminergic degeneration in preclinical PD models, are underway.
Previous studies in Parkinson's Disease (PD) models have shown promise with the use of recombinant adeno-associated virus serotype-2 (rAAV2)-neurturin (NRTN) [AAV2-NRTN] providing neuroprotection and behavioral improvements in preclinical models which subsequently resulted in several clinical studies in patients with PD.
This study provides Class IV evidence that bilateral neurturin gene delivery (CERE-120) to the SN plus putamen in patients with moderately advanced PD is feasible and safe.
Contrariwise, very limited success was obtained in clinical studies, where glial cell line-derived neurotrophic factor and neurturin were the neurotrophic factors of choice for Parkinson's disease therapy.
This may be best exemplified by adeno-associated virus serotype-2-neurturin (CERE-120), a viral-vector construct designed to deliver the neurotrophic factor, neurturin to degenerating nigrostriatal neurons in Parkinson's disease.