Muscle Diseases Research 1.2 : Pharmacological Therapies I Flashcards
What is the gene regulation hypothesis for dystrophic necrosis?
In the absence of dystrophin, there is a disregulation of other proteins as it is closely associated with them, possibly gene inducing proteins, affecting gene regulation.
What is the vascular hypothesis for dystrophic necrosis?
Loss of signalling for oxygen transport via NO in blood vessels.
Creates an oxygen deficient environment, and muscles become ischaemic when working muscles demand oxygen.
What happens to mice with an NO knockout?
They dont have a muscular disease.
What is the inflammatory hypothesis for dystrophic necrosis?
Disregulation of the normal injury-repair mechanism, excessive inflammatory signature, rise in inflammatory proteins.
What is needed to recruit satellite cells? How is this a problem in DMD?
Inflammation needed to recruit satellite cells. Excessive inflammation is seen in DMD and indicates disrgulation.
How is fibrosis caused?
Continuous cycle of trauma-repir means replacement of muscle fibres with collagen, which is non-contractile.
Why is fibrosis an issue for treatment?
Is a physical barrier betwen drug and muscle.
Isn’t reversible either.
What effect does fibrosis have on muscles?
Makes them stiffer and reduces strength.
Why does fibrosis affect timing of the intervention?
Fibrosis is irreversible, and prevention of fibrosis needed to efficiently deliver drugs and preserve muscle fibres.
Do animal models always translate to humans?
No.
What are the functions of corticosteroids?
Maintain/decrease muscle fibre size, and are catabolic.
What effect do corticosteroids have on inflammation?
Reduces chronic inflammation.
What effect do corticosteroids have on muscle strength?
Small increase, but not directly, rather a preservation of muscle strength.
What effect do corticosteroids have on fibrosis?
Slows fibrotic deposition.
What are the side effects of corticosteroids (name 4)?
Weight gain, high blood pressure, ulcers and bone growth inhibition.
What is the gold standard of DMD treatment?
Corticosteroids
What are new DMD drugs compared to as a standard?
Corticosteroids, the gold standard.
Does corticosteroid treatment interact with other treatments? If a better drug is found, should it replace corticosteroids? Why?
Yes they do.
The new drug should replace corticosteroids due to its many side effects.
How do anabolic agents affect muscle size and susceptibility?
Increases muscle size, and potentially reduce inflammation.
However, may make it more susceptible to damage.
What happens to mice with myostatin knockout?
Much bigger muscles.
What happens to myostatin with age?
Increases, is a sarcopenia contributor.
What is one way to reduce myostatin besides a knockout?
Antibodies to inhibit.
What is an anabolic treatment approach to DMD, and when is this normally released? What are some side effects?
IGF1 - growth hormone, released after overload and injury
Increases muscle mass and strength
Side effects include possible tumour formation due to growth effects - less likely
Increase existing tumour growth - more likely
How much of an anabolic agent would be administered?
Restored to normal levels, DMD patients may need more.
