Myopathies

Question 1

What is a myopathy?

Answer 1

Muscle disease

Question 2

What is sarcopenia?

Answer 2

Loss of muscle mass with age

Question 3

What are satellite cells?

Answer 3

Stem cells present in the muscle between the sarcolemma and basal lamina.

Involved in remodelling, repair and growth of muscle

Question 4

What are the features of skeletal muscle?

Answer 4

sarcomere -> myofibrils -> muscle fibres

Multinucleated cells

Fibres are surrounded by cell membrane called the sarcolemma

Sarcolemma further surrounded by basal lamina

Question 5

Why can muscle fibres not divide?

Answer 5

They contain post-mitotic nuclei

So satellite cells are the only ones contributing to remodelling of muscle

Question 6

What is muscular dystrophy?

Answer 6

A group of 8 inherited disorders each characterised by the gene mutation that leads to a change in protein expression

Question 7

What is congenital MD?

Answer 7

A combination of the 7 MDs

Question 8

What is the appearance of normal muscle?

Answer 8

Muscle fibres are polyglonal, similar in size and tightly packed

Sarcolemmal nuclei

Question 9

What is the appearance of MD muscle?

Answer 9

Muscle fibres vary in shape

More nuclei, found in center of the muscle fibres

Basophilic

Fibrosis and adipose tissue

Infiltration of inflammatory cells causes necrotic tissue

Question 10

What are possible defective genes that can lead to MD?

Answer 10

Dystrophin - found under muscle fibres
Emerin/ lamin - found in envelope surrounding nucleus
Sarcoglycans - cross the muscle fiber membrane

Question 11

What is Duchenne Muscular dystrophy?

Answer 11

Inherited, X-linked disorder caused by a mutation in the gene coding for dystrophin

Question 12

How does DMD progress?

Answer 12

Muscle fibres are weak and break easily

This triggers a cycle of degradation and regeneration

The regeneration of muscle tissue cannot keep up with degradation so eventually the muscle fibres are replaced with adipose and fibrotic tissue

Question 13

What is the dystrophin gene?

Answer 13

A mutation in this causes DMD

One of the largest genes in the human body

79 exons
0.02% of the muscle fibre weight

Question 14

What is the dystrophin-associated complex?

Answer 14

Dystrophin is a part of a complex called the dystrophin-associated glycoprotein molecule

Associated with many proteins found:
Intracellularly
Extracellularly
Freely

A defect in any of the genes coding for the parts of this complex leads to MD

Question 15

Is there a cure for MD?

Answer 15

No

There are currently lots of scientific research and clinical trials

Mdx mouse - model for DMD

Question 16

What are potential treatments for MD?

Answer 16

Restoration of missing or defective proteins
Replacement of dystrophin with similar proteins
Prevent death of muscle fibres
Enhance repair and regeneration
Prevent inflammation or fibrosis

Question 17

What are methods to restore missing or defective proteins?

Answer 17

Stem cell therapy
Exon skipping - skip mutated genes
Genome editing
Stem cells - restore defective proteins

Question 18

How can you enhance repair and regeneration in the muscle?

Answer 18

Improve the number of satellite cells in the muscle

Question 19

What protein can we replace dystrophin with?

Answer 19

Utrophin

Found in nerve terminals and developing muscle