I wanted to share this with everyone.

British Journal of Pharmacology, 2010) Co-administration of ibuprofen and nitric oxide is an effective experimental therapy for muscular dystrophy, with immediate applicability to humans

Clara Sciorati, Roberta Buono, Emanuele Azzoni, Silvana Casati, Pierangela Ciuffreda, Grazia D'Angelo, Dario Cattaneo, Silvia Brunelli, Emilio Clementi - Italy

Background and purpose: Current therapies for muscular dystrophy are based on corticosteroids. Significant side effects associated with these therapies have prompted several studies aimed at identifying possible alternative strategies. As inflammation and defects of nitric oxide (NO) generation are key pathogenic events in muscular dystrophies, we have studied the effects of combining the NO donor isosorbide dinitrate (ISDN) and the non-steroidal anti-inflammatory drug ibuprofen.

Experimental approach: α-Sarcoglycan null mice were treated for up to 8 months with ISDN (30 mg/kg) plus ibuprofen (50 mg/kg) administered daily in the diet. Effects of ISDN and ibuprofen alone were assessed in parallel. Drug effects on animal motility and muscle function, muscle damage, inflammatory infiltrates and cytokine levels, as well as muscle regeneration including assessment of endogenous stem cell pool, were measured at selected time points.

Key results: Combination of ibuprofen and ISDN stimulated regeneration capacity, of myogenic precursor cells, reduced muscle necrotic damage and inflammation. Muscle function in terms of free voluntary movement and resistance to exercise was maintained throughout the time window analysed. The effects of ISDN and ibuprofen administered separately were transient and significantly lower than those induced by their combination.

Conclusions and implications: Co-administration of NO and ibuprofen provided synergistic beneficial effects in a mouse model of muscular dystrophy, leading to an effective therapy. Our results open the possibility of immediate clinical testing of a combination of ISDN and ibuprofen in dystrophic patients, as both components are approved for use in humans, with a good safety profile.

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Comment by Ofelia Marin on April 23, 2010 at 9:34pm
They tested these in DMD patients, pilot trial, I would like to see those results. Also discussed at TACT:


In summary, based on the preclinical data with the combination of these drugs in mdx mice, TACT recommended further dose ranging and PK studies in mice and in pilot human studies to define if an effective level of drug is likely without unacceptable side effects. As proposed by the applicants, TACT believed that a trial of these agents in the non-ambulant DMD population could be feasible provided certain aspects of the trial design, as outlined in the report to the applicant, were addressed. From a regulatory perspective involvement of EMA and FDA at an early stage including orphan drug designation was recommended, as was the approach of treating these compounds as "two products simultaneously".

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