Flashcards in Duchenne Muscular Dystrophy Deck (14)
What is the cause of Duchenne muscular dystrophy?
result of truncating mutations in the DMD gene
What is the clinical manifestations of DMD?
results in a lack of expression of the dystrophin protein in muscle fibers
Describe the therapeutic construct delivered.
therapeutic minidystrophin construct
Name the vector used to deliver the construct.
intramuscular adeno-associated virus-mediated delivery; a gene therapy vector designed to restore muscle function
Describe the assay used to quantify the peripheral T-cell response to the dystrophin
enzyme-linked immunospot assay:
interferon (IFN) gamma enzyme linked immunospot (ELISPOT) - peripheral blood mononuclear cells (PBMC) isolated on Ficoll Hypaque gradients are cultured with synthetic peptides that span the entire dystrophin protein.
Peptide mapping pools were used to further localize the immune response. Spot forming cells (SFCs) were counted. Positive exceeded 15 SFCs/10^6 PBMCs.
List the immune cells dominating the immune response to dystrophin.
Tcells CD4 helper and/or CD8+ cytotoxic
List the difference in response in patients treated with corticosteroids compared to the untreated group.
treatment with either prednisone or deflazacort decreases risk of anti-Dystropin T cell immunity
What type of chromosomal link is involved with DMD?
What is the result of the absence of expression of the dystrophin protein in skeletal and cardiac muscles?
myofiber degeneration occurs with subsequent accelerated rounds of myofiber regeneration and degeneration leading to myofiber loss and replacement of contractile fibers with fibrosis and fat
When do symptoms typically present in DMD?
3-5: gait disturbance
12: loss of ambulation
typically lead to death by end of second decade
What are the current therapies?
What effect might deflazacort and prednisone have in Tcell response?
differential effect in modulation Tcell response in boys with DMD
What cytokines did the CD4 cells fail to produce in the DMD patients?
tumor necrosis factor (TNF) alpha
interleukin (IL) 2