The investigational therapy givinostat improved muscle morphology and function in mouse models of Duchenne muscular dystrophy (DMD), researchers found in a recently published study. The long-term (15 weeks) oral treatment was efficient in both mdx and D2.B10 mice, which represent mild and severe DMD phenotypes, respectively.

Licandro et al found that “the effect of givinostat in both grip strength and exhaustion tests was dose-dependent in both strains, and in D2.B10 mice, givinostat outperformed steroids at its highest dose.”

The study authors found a dose-dependent increase in the highest recorded value of maximal normalized strength (FNmax) after treatment with givinostat. In mdx mice, FNmax, treadmill distance run by the animals, and time to exhaustion improved to levels comparable to wild-type animals.

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Givinostat accumulated in muscle tissue up to 6 hours after administration, where it reached a concentration 4.5 times higher than in plasma. The concentration curve dropped after a few hours. Hence, the functional benefits were transient, but the authors still observed a difference during the decline phase when compared to wild-type animals.

In addition, Licandro et al used prednisone and deflazacort (Emflaza®) to compare the effect of givinostat treatment with that of standard glucocorticoid steroid treatment for DMD patients.

However, the results obtained for D2.B10 mice were more difficult to interpret due to protocol conditioning. For instance, D2.B10 mice received their treatment through their drinking water, rather than daily gavage. Though water consumption measurements did suggest that drug intake by D2.B10 mice was comparable to that of mdx mice, the researchers were not able to accurately monitor givinostat pharmacokinetics. Also, Licandro et al adopted protocol changes to safeguard animal well-being when evaluating their physical performance. 

For the sake of simplicity, the two DMD mouse strains here referred to as mdx and D2.B10 correspond to C57BL10ScSn-Dmdmdx/J as and D2.B10-Dmdmdx/J, respectively. These strains mimic different human LTBP4 haplotypes. 

The same Ltbp4 region is affected in both strains. On the one hand, a 12-amino acid insertion in mdx mice contributes to a mild DMD phenotype that resembles the human IAAM haplotype. On the other hand, a 12-amino acid deletion in D2.B10 mice contributes to a severe DMD phenotype that resembles the human VTTT haplotype.

Givinostat efficacy and safety in ambulatory DMD patients are currently being studied in a phase 3 clinical trial (NCT02851797). 


Licandro SA, Crippa L, Pomarico R, et al. The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 geneSkelet Muscle. 2021;11(1):19. doi:10.1186/s13395-021-00273-6

Clinical study to evaluate the efficacy and safety of givinostat in ambulant patients with Duchenne muscular dystrophy. August 2, 2016. Updated April 12, 2021. Accessed July 30, 2021.