Muscle Diseases Research 1.3 : Pharmacological Therapies II Flashcards
What is interleukin 15, and when is it released?
It is a myokine released by muscle during contraction.
What does interleukin 15 do?
Increases glucose uptake.
What does interleukin 15 do in DMD?
Significantly increases force of the diaphragm, but was in young subjects.
Significance may be due to early intervention and fibrosis prevention.
Give an example of a membrane sealant, and its effects.
Poloxamer 288
Plugs holes in membranes, can be tested using electroporated membranes
Prevented cardiac failure in mdx mice and restored membrane stability
Can be stacked with other treatments.
Which pump is believed to be impaired in DMD? How does this happen? What effect does this have?
Sarcoplasmic Ca2+ uptake pump. Over time, the damage-repair cycle of dystrophy impairs them. Less able to reuptake Ca2+, which builds up and activates damaging pathways.
What is the Ca2+ pump like in early DMD?
It works well, but increasingly deteriorates due to the damage-repair cycle.
What is Hsp72, and what does overexpression do to DMD?
Chaperone heat shock protein that lowers CK level, lowers fibrosis infiltration and improves Ca2+ pump function.
Increases muscle force.
How can Hsp72 be induced? Name two pathways.
A co-inducer can be used, doesnt induce directly, but will result in increased levels, bgp15.
Direct heat shock can be employed, anaesthetise and subject to warm temperature.
What is the more effective way of inducing Hsp72?
Using Bgp15 is more effective.
Does high Hsp72 levels induced by direct heat shock improve Ca2+ pump function?
No it doesn’t, only bgp15 does.
What effect does bgp15 have on kyphosis?
Reduced kyphosis.
Does bgp15 induced Hsp72 discriminate with age?
Yes it does, doesnt work as well in old mice. Kyphosis and fibrosis alleviation didnt translate well.
What is the problem with DMD subjects dying so early?
Only symptoms that manifest in early life can be seen. Because its rare for them to live to an old age, symptoms that only manifest in old DMD subjects can rarely be seen and characterised, and now need to be addressed as more DMD subjects live older.
Can anti-fibrotic drugs be used in DMD? How can they help if at all?
Yes they can be used to decrease fibrosis, but will not increase muscle function. But it would be best to do antifibrotic first, then increase hypertropy after to increase function, so the drug can reach the muscle.
