Development of nonviral vectors targeting the brain as a therapeutic approach for Parkinson's disease and other brain disorders

Hayate Javed, Sindhu A. Menon, Karima M. Al-Mansoori, Abdelmojib Al-Wandi, Nour Majbour, Mustafa T. Ardah, Shiji Varghese, Nishant Vaikath, M. Emdadul Haque, Mimoun Azzouz, Omar Ali El-Agnaf

Research output: Contribution to journalArticle

14 Citations (Scopus)


Parkinson's disease (PD) is a debilitating neurodegenerative disease characterized by tremor, rigidity, bradykinesia, and postural instability, for which there is no effective treatment available till date. Here, we report the development of nonviral vectors specific for neuronal cells that can deliver short interfering RNA (siRNA) against the α-synuclein gene (SNCA), and prevent PD-like symptoms both in vitro and in vivo. These vectors not only help siRNA duplexes cross the blood-brain barrier in mice, but also stabilize these siRNAs leading to a sustainable 60-90% knockdown of α-synuclein protein. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine rapidly develop PD-like symptoms which were significantly alleviated when SNCA was knocked down using our vectors. Together, our data not only confirm the central role of α-synuclein in the onset of PD, but also provide a proof of principle that these nonviral vectors can be used as novel tools to design effective strategies to combat central nervous system diseases.

Original languageEnglish
Pages (from-to)746-758
Number of pages13
JournalMolecular Therapy
Issue number4
Publication statusPublished - 1 Apr 2016


ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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