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Cited by 15Multiple Sclerosis Research StudiesMitochondrial Function and PathologyNeurological Disorders and Treatments

Neuroprotection induced by dexpramipexole delays disease progression in a mouse model of progressive multiple sclerosis

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Buonvicino, Daniela, Ranieri, Giuseppe, Pratesi, Sara, Gerace, Elisabetta, Muzzi, Mirko, Guasti, Daniele, Tofani, Lorenzo, Chiarugi, Alberto·2020·British Journal of Pharmacology
DOI 10.1111/bph.15058PMC PMC7312322
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Abstract

Background and Purpose: Drugs able to counteract progressive multiple sclerosis (MS) represent a largely unmet therapeutic need. Even though the pathogenesis of disease evolution is still obscure, accumulating evidence indicates that mitochondrial dysfunction plays a causative role in neurodegeneration and axonopathy in progressive MS patients. Here, we investigated the effects of dexpramipexole, a compound with a good safety profile in humans and able to sustain mitochondria functioning and energy production, in a mouse model of progressive MS. Experimental Approach: Female non‐obese diabetic mice were immunized with MOG 35–55. Functional, immune and neuropathological parameters were analysed during disease evolution in animals treated or not with dexpramipexole. The compound's effects on bioenergetics and neuroprotection were also evaluated in vitro. Key Results: We found that oral treatment with dexpramipexole at a dose consistent with that well tolerated in humans delayed disability progression, extended survival, counteracted reduction of spinal cord mitochondrial DNA content and reduced spinal cord axonal loss of mice. Accordingly, the drug sustained in vitro bioenergetics of mouse optic nerve and dorsal root ganglia and counteracted neurodegeneration of organotypic mouse cortical cultures exposed to the adenosine triphosphate‐depleting agents oligomycin or veratridine. Dexpramipexole, however, was unable to affect the adaptive and innate immune responses both in vivo and in vitro. Conclusion and Implication: The present findings corroborate the hypothesis that neuroprotective agents may be of relevance to counteract MS progression and disclose the translational potential of dexpramipexole to treatment of progressive MS patients as a stand‐alone or adjunctive therapy.

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Cited by

Sorted by citations

Authors
Buonvicino, D., Ranieri, G., Pratesi, S., Gerace, E., Muzzi, M., Guasti, D., Tofani, L., & Chiarugi, A.
Affiliations
  • University of Florence (IT)
  • Azienda Ospedaliero-Universitaria Careggi (IT)
Corresponding author
Buonvicino, Daniela
ORCID
Venue
British Journal of Pharmacology
Publisher
Wiley
Published
2020-04-18
Volume
177
Issue
14
Pages
3342-3356
ISSN
  • 0007-1188 (ISSN-L)
  • 1476-5381
DOI
10.1111/bph.15058
PMC
PMC7312322
OpenAlex
W3012836604
Cited by
15
References
2
Citations by year
2026: 2 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 2
FWCI
1.15
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • British Journal of Pharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Florence Research (University of Florence) (submittedVersion)
Funders
Associazione Italiana per la Ricerca sul Cancro
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
Keywords
progressive multiple sclerosis, neuroprotection, mitochondrial dysfunction, bioenergetics, mitochondrial DNA, axonal loss, spinal cord, optic nerve, dorsal root ganglia, neurodegeneration, oligomycin, veratridine, disability progression, disease-modifying therapy
MeSH terms
Neuroprotection, Pramipexole, Animals, Diabetes Mellitus, Experimental, Female, Humans, Multiple Sclerosis, Disease Progression, Mice

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