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Brain. 2019 Feb 1;142(2):312-321. doi: 10.1093/brain/awy328.

Self-assembling vascular endothelial growth factor nanoparticles improve function in spinocerebellar ataxia type 1.

Author information

1
Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
2
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
3
Department of Pathology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA.
4
Departments of Materials and Science and Engineering, Chemistry, Medicine, and Biomedical Engineering, Northwestern University, Evanston, IL USA.
5
Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois, USA.
6
Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine Chicago, Illinois, USA.

Abstract

There is increasing appreciation for the role of the neurovascular unit in neurodegenerative diseases. We showed previously that the angiogenic and neurotrophic cytokine, vascular endothelial growth factor (VEGF), is suppressed to abnormally low levels in spinocerebellar ataxia type 1 (SCA1), and that replenishing VEGF reverses the cerebellar pathology in SCA1 mice. In that study, however, we used a recombinant VEGF, which is extremely costly to manufacture and biologically unstable as well as immunogenic. To develop a more viable therapy, here we test a synthetic VEGF peptide amphiphile that self-assembles into nanoparticles. We show that this nano-VEGF has potent neurotrophic and angiogenic properties, is well-tolerated, and leads to functional improvement in SCA1 mice even when administered at advanced stages of the disease. This approach can be generalized to other neurotrophic factors or molecules that act in a paracrine manner, offering a novel therapeutic strategy for neurodegenerative conditions.

PMID:
30649233
PMCID:
PMC6351780
[Available on 2020-02-01]
DOI:
10.1093/brain/awy328

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