Towards precision nanomedicine for cerebrovascular diseases with emphasis on Cerebral Cavernous Malformation (CCM)

ABSTRACT

Introduction: Cerebrovascular diseases encompass various disorders of the brain vasculature, such as ischemic/hemorrhagic strokes, aneurysms, and vascular malformations, also affecting the central nervous system leading to a large variety of transient or permanent neurological disorders. They represent major causes of mortality and long-term disability worldwide, and some of them can be inherited, including Cerebral Cavernous Malformation (CCM), an autosomal dominant cerebrovascular disease linked to mutations in CCM1/KRIT1, CCM2, or CCM3/PDCD10 genes.

Areas covered: Besides marked clinical and etiological heterogeneity, some commonalities are emerging among distinct cerebrovascular diseases, including key pathogenetic roles of oxidative stress and inflammation, which are increasingly recognized as major disease hallmarks and therapeutic targets. This review provides a comprehensive overview of the different clinical features and common pathogenetic determinants of cerebrovascular diseases, highlighting major challenges, including the pressing need for new diagnostic and therapeutic strategies, and focusing on emerging innovative features and promising benefits of nanomedicine strategies for early detection and targeted treatment of such diseases.

Expert opinion: Specifically, we describe and discuss the multiple physico-chemical features and unique biological advantages of nanosystems, including nanodiagnostics, nanotherapeutics, and nanotheranostics, that may help improving diagnosis and treatment of cerebrovascular diseases and neurological comorbidities, with an emphasis on CCM disease.

KEYWORDS:

• Central nervous system (CNS)
• cerebrovascular diseases
• cerebral cavernous malformation (CCM)
• inflammation
• oxidative stress
• nanosystems
• nanodiagnostics
• nanotherapeutics
• nanotheranostics
• nose-to-brain delivery

Article highlights

• Cerebrovascular diseases, including strokes, aneurysms, and vascular malformations, are leading causes of mortality and adult long-term disability worldwide.

• A few types of cerebrovascular diseases can be inherited, including Cerebral Cavernous Malformation (CCM).

• Oxidative stress and inflammation are increasingly recognized as major disease hallmarks and therapeutic targets of distinct of cerebrovascular diseases.

• Nanomedicine is emerging as a promising and effective strategy for early detection and targeted treatment of cerebrovascular diseases and neurological comorbidities.

• This review critically describes the physico-chemical features and biological advantages of nanosystems, including nanodiagnostics, nanotherapeutics and nanotheranostics, that may help improving diagnosis and treatment of cerebrovascular diseases and neurological comorbidities.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors are grateful to CCM Italia, the Italian Research Network for Cerebral Cavernous Malformation (https://www.ccmitalia.unito.it), and the Associazione Italiana Angiomi Cavernosi (AIAC) Onlus (https://www.aiac.unito.it), including its president Massimo Chiesa, for fundamental support, and Santina Barbaro for helpful collaboration. The authors also thank Pier Paolo Pompa, Gaudenzio Inverso and Alessandra Bordon for careful reading of the manuscript and helpful discussion. This article is dedicated to the memory of Rosa Giunta and Fortunato Barbaro.

Additional information

Funding

This work was supported by the Telethon Foundation (grant GGP15219 to SF Retta), the Fondazione CRT (Cassa di Risparmio di Torino) (project grant ‘Cerebro-NGS.TO’ to SF Retta), the Università degli Studi di Torino (Local Research Funding 2016-19 to SF Retta).