Preclinical nanomedicines for polyglutamine-based neurodegenerative diseases
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AbstractPolyglutamine (PolyQ) diseases, such as Huntington’s disease and several types of spinocerebellar ataxias, are dominantly inherited progressive neurodegenerative disorders and characterized by the presence of expanded CAG trinucleotide repeats in the respective disease locus of the patient genomes. Patients with polyQ diseases currently need to rely on symptom-relieving treatments because disease-modifying therapeutic interventions remain scarce. Many disease-modifying therapeutic agents are now under clinical testing for treating polyQ diseases, but their delivery to the brain is often too invasive (e.g., intracranial injection) or inefficient owing to in vivo degradation and clearance by physiological barriers (e.g., oral and intravenous administration). Nanoparticles provide a feasible solution for improving drug delivery to the brain, as evidenced by an increasing number of preclinical studies that document the efficacy of nanomedicines for polyQ diseases over the past 5–6 years. In this review, we present the pathogenic mechanisms of polyQ diseases, the common animal models of polyQ diseases for evaluating the efficacy of nanomedicines, and the common administration routes for delivering nanoparticles to the brain. Next, we summarize the recent preclinical applications of nanomedicines for treating polyQ diseases and improving neurological conditions, placing an emphasis on antisense oligonucleotides, small peptide inhibitors, and small molecules as the disease-modifying agents. We conclude with our perspectives of the burgeoning field of “nanomedicines for polyQ diseases”, including the use of inorganic nanoparticles and potential drugs as next-generation nanomedicines, development of higher-order animal models of polyQ diseases, and importance of “brain-nano” interactions.
Acceptance Date25/06/2020
All Author(s) ListLeo Kit Cheung Lee, Lok I Leong, Yao Liu, Meihua Luo, Ho Yin Edwin Chan, Chung Hang Jonathan Choi
Journal nameMolecular Pharmaceutics
Volume Number18
Issue Number2
PublisherAmerican Chemical Society
Pages610 - 626
LanguagesEnglish-United States
Keywordsneurodegenerative diseases, Huntington’s disease, polyglutamine, brain delivery, nanoparticles, nanomedicine

Last updated on 2021-07-05 at 00:41