Abstract:
Dysferlinopathies include Limb-Girdle Muscular Dystrophy type 2B and Miyoshi Myopathy, which exhibit
an autosomal recessive inheritance pattern of the dysferlin gene and characteristic inflammatory infiltrate
in muscle. A study of prospective treatment options was conducted on SJL/J mice, a natural model for dysferlinopathy.
The animals are immunocompetent but have elevated levels of circulating T-cells. A baseline
termination of SJL/J mice was made at 14 weeks, and differential leukocyte counts determined for these
animals through microscopy. After administration of resveratrol and Coenzyme Q10 exclusively and in combination
to the four treatment groups for approximately three months, the remaining six groups (negative
and positive controls as well as four treatment groups) were terminated and differential leukocyte counts
once again determined. Eosinophil counts were significantly higher in the baseline termination group than
all other experimental groups assessed except for the negative control SWR/J mice, possessing normal
muscle and used in research as a general purpose strain. Eosinophil granules are suggested to reduce inflammation
caused by other leukocytes. At onset of dysferlinopathy between four and six weeks of age, the
increase in eosinophil counts could very likely be a compensation mechanism to decrease initial inflammation
in the muscular tissues of the dysferlinopathic mice. Neutrophil counts of the baseline termination
group were significantly higher only when compared to the resveratrol/Coenzyme Q10 combination group.
Neutrophils are linked to early inflammatory responses and often sensitised in self-antigen recognition
characteristic of autoimmune disease, a known complication in the SJL strain. Thus the higher neutrophil
count in the six week old mice is probably related to inflammation at disease onset, but may also be indicative
of autoimmunity; whereas the eosinophil counts may possibly play a more definitive role in the pathogenesis
of dysferlinopathy. Further morphological studies will serve to clarify the roles of these leukocytes
in dysferlinopathy.
