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

Yuan Shih Hu, Jeehaeh Do, Chandrakanth Reddy Edamakanti, Ameet R. Kini, Marco Martina, Samuel I. Stupp, Puneet Opal*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)312-321
Number of pages10
JournalBrain
Volume142
Issue number2
DOIs
StatePublished - Feb 1 2019

Keywords

  • VEGF
  • nanoparticle
  • neurodegeneration
  • neurotrophic therapy
  • spinocerebellar ataxia type 1

ASJC Scopus subject areas

  • Clinical Neurology

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