Objective: We propose to determine a therapeutic strategy based on adoptive transfer of macrophages reprogrammed for recombinant IGF2 (rIGF2) treatment in PD preclinical model.
Background: Parkinson disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, which causes motor deficits. The most common features of PD are the presence of α-synuclein (α-syn) protein aggregates. Accumulate evidence support that the chronic inflammatory response could mediate the neurodegeneration process in PD patients. This increase in proinflammatory activity is induced by α-synuclein misfolded protein. Moreover, the growth factor Insulin-like growth factor 2 (IGF2) it has been described as a possible modulator of the inflammatory response in macrophages. IGF2 decrease in blood samples from PD patient.
Method: We delivered macrophages reprogrammed with rIGF2 by intravenous injection in ASO mice and we evaluate, motor performance, inflammatory response, α-syn accumulation and neuroinflammation response. Also using cellular PD model, we determine the effect IGF2 signaling on cell viability and mitochondrial dysfunction.
Results: Our results described a significant increase of proinflammatory markers and TLR4 expression in PD patients and preclinical model. Also, our result indicates the adoptive transfer of macrophages reprogrammed for rIGF2, prevents the motor symptoms and neuroinflammation in PD preclinical model. In addition, we demonstrated that IGF2 signaling are capable to prevent cell death and mitochondrial damage induced by α-syn misfolded.
Conclusion: These data suggest IGF2 as an interesting candidate for future treatment in PD as an immunomodulator agent.
To cite this abstract in AMA style:
FG. Grünenwald, MC. Cisternas, DS. Sepulveda, TH. Huerta, CJ. Jerez, RP. Pacheco, RLV. Vidal. IGF2 Induce Neuroprotection in PD Preclinical Models by Modulation of Immune Response. [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/igf2-induce-neuroprotection-in-pd-preclinical-models-by-modulation-of-immune-response/. Accessed October 7, 2024.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/igf2-induce-neuroprotection-in-pd-preclinical-models-by-modulation-of-immune-response/