Treatment with rGDF11 does not improve the dystrophic muscle pathology of mdx mice.
BACKGROUND
Duchenne muscular dystrophy (DMD) is an inherited lethal muscle wasting disease characterized by cycles of degeneration and regeneration, with no effective therapy. Growth differentiation factor 11 (GDF11), a member of the TGF-β superfamily and myostatin homologous, has been reported to have the capacity to reverse age-related skeletal muscle loss. These initial findings led us to investigate the ability of GDF11 to promote regeneration in the context of muscular dystrophy and determine whether it could be a candidate to slow down or reverse the disease progression in DMD.


RESULTS
Here, we delivered recombinant GDF11 (rGDF11) to dystrophin-deficient mice using the intra-peritoneal route for 30 days and evaluated histology and function in both steady-state and cardiotoxin-injured muscles. Our data confirmed that treatment with rGDF11 resulted in elevated levels of this factor in the circulation. However, this had no effect on muscle contractility nor on muscle histology. Moreover, no difference was found in the number of regenerating myofibers displaying centrally located nuclei. On the other hand, we did observe increased collagen content, which denotes fibrosis, in the muscles of rGDF11-treated dystrophic mice.


CONCLUSIONS
Taken together, our findings indicate no beneficial effect of treating dystrophic mice with rGDF11 and raise caution to a potential harmful effect, as shown by the pro-fibrotic outcome.
Lillehei Heart Institute, Department of Medicine, University of Minnesota, 4-128 CCRB, 2231 6th St. SE, Minneapolis, MN 55455 USA.
Fabrizio
F
Rinaldi
Lillehei Heart Institute, Department of Medicine, University of Minnesota, 4-128 CCRB, 2231 6th St. SE, Minneapolis, MN 55455 USA.|Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Yu
Y
Zhang
Lillehei Heart Institute, Department of Medicine, University of Minnesota, 4-128 CCRB, 2231 6th St. SE, Minneapolis, MN 55455 USA.|Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN), México, D.F. Mexico.
Ricardo
R
Mondragon-Gonzalez
Tonus Therapeutics, Williamsville, NY USA.
Jeffrey
J
Harvey
Lillehei Heart Institute, Department of Medicine, University of Minnesota, 4-128 CCRB, 2231 6th St. SE, Minneapolis, MN 55455 USA.
Rita C R
RCR
Perlingeiro
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal; D005355:Fibrosis; D055412:Growth Differentiation Factors / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007274:Injections, Intraperitoneal; D008297:Male; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects; D024510:Muscle Development / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D011994:Recombinant Proteins / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects; D013997:Time Factors
D019485:Bone Morphogenetic Proteins; D055412:Growth Differentiation Factors; D011994:Recombinant Proteins
Duchenne muscular dystrophy; Fibrosis; GDF11; Muscle regeneration