4. Remyelination in multiple sclerosis Flashcards
How are myelin and oligodendrocytes linked?
Oligodendrocytes - cells responsible for producing myelin + feeding nerve cells
Myelin - fatty substance that forms a protective sheath around nerve fibers (axons) in the central nervous system (CNS)
What other cells apart from oligodendrocytes also deposite myelin?
Schwann cells - produce myelin - but not in CNS - in the peripheral nervous system (PNS) - which includes nerves outside of the brain and spinal cord
How does myelin content change in the brain throughout life?
- Infancy: little myelin when born - increases
Increase in myelination -> increase in physical + mental skills
- Adolescence: myelin content peaks
- Middle age and later: myelin content decreases from 40
What is multiple sclerosis?
Multiple sclerosis (MS) - a chronic autoimmune disease - affects CNS (brain and spinal cord) - immune system - T-cells inflammation - mistakenly attacks the myelin sheath - neurodegenerative disease
Lose myelin - lose white brain matter
Explain what are the trends in MS progression
MS progression - 2 phases:
- Inflammation: initial phase - comes and goes in waves
- Neurodegeneration: following phase - disease progression - disability sticks and gets worse
What drugs should be used for MS treatment in the different disease phases
Phase I: inflammation -> anti-inflammatory (currently exist)
Phase II: neurodegeneration -> neuroprotective therapies (currently in development)
What challenges need to be tackled to prevent MS progression?
What is the cellular mechanism in MS progression? what happens to neurons?
No OPC recruitment -> no myelin deposition -> mitochondrial response down the axon -> axonal degeneration
Do all patients with MS experience same neurodegeneration?
No, variable rates of degeneration between patients with MS
What are the different approaches to studying remyelination?
What are the techniques used to study myelin regeneration?
Why has remyelination not been achieved?
Remyelination helps people but at varying levels - some people better regenerate than others - potentially genetic -
Depends on:
- region dependent - brain / spine
- disease dependent
- person dependent
What are the potential approaches myelin regeneration in MS
GEMINI:
Potential Approaches to Myelin Regeneration
Stimulating endogenous repair:
Drugs: Certain medications may be able to stimulate the body’s own repair mechanisms, encouraging the growth of new myelin.
Stem cells: Stem cells can be transplanted into the brain or spinal cord, where they may differentiate into oligodendrocytes, the cells that produce myelin.
Replacing damaged myelin:
Synthetic myelin: Scientists are developing synthetic materials that could potentially mimic the function of natural myelin.
Engineered cells: Genetically engineered cells could be used to produce myelin in the damaged areas of the brain and spinal cord.
What are the potential limitations in myelin regeneration in MS?
GEMINI:
Challenges and Limitations
Despite promising research, there are still significant challenges to overcome:
Immune system interference: The immune system itself can hinder myelin regeneration, as it is often the cause of the initial damage.
Scar tissue formation: Scar tissue can form in damaged areas, preventing the growth of new myelin.
Limited effectiveness: Even if myelin regeneration is achieved, the extent of recovery may be limited, especially in cases of severe damage.
What is a good experimental approach in studying patients tryong to find the underlying genetic cause of MS?
Sequencing
What is wrong with MS oligodendrocytes?
MS oligodendrocytes misbehave - myelinate nerve cell bodies instead of axons
How could better non-defective oligodendrocyte transplantation work?
CRISPR editing oligodendrocytes - enhance migration to lesion sites
What is the cell composition of MS lesions
Why is it difficult to find one universal therapy for MS?
MS very variable between different patinets - genetic influences? - need different therapies - maybe even mix to combat MS
Types of drugs needed for MS treatment
Summary points for discussion about MS and myelination regeneration for treating it
