Fullerene (ABS-75) Treatment Reduces Disease Progression in Mice

Fullerene (ABS-75) Treatment Reduces Disease Progression and Axonal Loss in MOG-Induced Progressive EAE in NOD Mice

OBJECTIVE:

We tested whether Fullerene (ABS-75) treatment is able to reduce disease progression and axonal loss in MOG-induced progressive EAE in NOD mice.

BACKGROUND:

Inflammation-induced oxidative stress can lead to axonal degeneration, which is felt to be a major determinant of progressive neurological disability in Multiple Sclerosis (MS).  Water-soluble derivatives of fullerenes are a unique class of allotropic form of carbon compounds with potent antioxidant properties.  

DESIGN/METHODS:

10 week old mice were immunized with 150 ug of MOG 35-55 peptide in CFA followed by pertussis (whooping cough) toxin.  Disease is characterized by an attack followed by a progressive phase with chronic clinical impairment.  Following the first attack, animals were distributed into different groups with similar disease courses and treated intraperitoneally (injected) either with 200ul of a 1uM fullerene solution or vehicle (DMSO 2% in PBS) every day until termination of the experiment on day 63.

RESULTS:

We found that ABS-75 treatment initiated after disease onset reduced the clinical progression of chronic EAE in NOD mice (treated vs. control, p < 0.05).  Fullerene ABS-75 consists of a C60 carbon fullerene core to which a known NMDA receptor ligand (organic molecule) was attached. ABS-75 treatment also reduced axonal loss and demyelination (as evaluated by silver and Luxol fast blue staining, respectively) in the white matter of mice. ABS-75 treated animals also showed reduction in CD11b+ infiltration and astrogliosis (inflammation) as compared to vehicle-treated group.

CONCLUSIONS/RELEVANCE:

Our data demonstrate a neuroprotective effect of a treatment with a fullerene compound combined with a NMDA receptor ligand that may have applicability in the treatment of progressive MS and other neurodegenerative diseases.

Category - MS and Related Diseases

SubCategory - Basic Science

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Alexandre S. Basso, Dan Frenkel, Boston, MA,

Sanja Petrovic-Stojkovic, Lindsay Puckett, Alon Monsonego, Boston,

Michael Gozin, Tel Aviv, Israel,

Howard Weiner, Brookline, MA