Beneficial effects of anti-inflammatory therapy in a mouse model of Niemann-Pick disease type C1

Innovative Therapeutic Approaches for Improving Patient Life Condition with a Neurological Lysosomal Disease

“…Similar results have recently been observed with various antioxidant treatments in other LSD models, such as in the NPC1 mouse (Bascunan-Castillo et al, 2004;Smith et al, 2009). However, some caution is required in interpreting these data, as we tested only one time point looking at biochemical and molecular changes in brain, liver and spleen tissues.…”

“…Indeed, several studies have recently shown that anti-inflammatory treatments, using nonsteroidal anti-inflammatory drugs (NSAIDs) significantly slowed the clinical course of both Sandhoff and Niemann-Pick type C1 diseases (Jeyakumar et al, 2003;Jeyakumar et al, 2004;Smith et al, 2009). It has also been shown by our group in the MPS IIIA mouse models, following-up several inflammation markers (Arfi et al, 2011).…”

“…NSAID could also be combined with other therapies targeting the primary defect, aiming at additive or synergistic benefit. However, further studies are necessary to characterize and maybe correlate a potential clinical improvement to the molecular and biochemical effects observed in aspirin-treated mice (Jeyakumar et al, 2004;Smith et al, 2009). In addition, careful preclinical and clinical studies would be required to determine whether these findings extrapolate to the human disease.…”

Multi-system disorders of glycosphingolipid and ganglioside metabolism

“…This indicates that multiple infl ammatory pathways participate. Nonsteroidal cyclooxygenase-dependent antiinfl ammatory drugs (e.g., indomethacin, aspirin, and ibuprofen) extended the lifespans of Sandhoff disease and NPC1 mice ( 240,242 ). In Sap A Ϫ / Ϫ mice, such treatment suppressed only early, but not later, proinfl ammation, indicating involvement of the cyclooxygenase pathway, but it is not the major infl ammatory pathogenic pathway (Barnes et al, unpublished observations).…”

Relative efficacy of nicotinamide treatment of a mouse model of infantile Niemann-Pick C1 disease

“…In the meantime, various common medications and/or food additives may ameliorate symptoms. The anti-inflammatory agents ibuprofen (Smith, et al, 2009) andvitamin E (Bascunan-Castillo, et al, 2004;Xu, et al, 2009) have been beneficial in animal models while curcumin has not much (Borbon, et al, 2012). Recently, histone deacetylase (HDAC) inhibitors have been proposed as drugs for the disease (Pipalia, et al, 2011).…”