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?
- promote nerve survival
- increase re-myelination
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?
- oligodendroglia
- migration
- differentiation
- mature oligodendrocyte remyelination
What are the techniques used to study myelin regeneration?
- primary oligo culture
- co-culture
- slice culture
- in vivo
Why has remyelination not been achieved?
Remyelination helps people but at varying levels - some people better regenerate than others - potentially genetic
Remyelination success depends on:
- region dependent - brain / spine
- disease dependent
- person dependent
What are the potential approaches for myelin regeneration in MS
GPT:
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?
GPT:
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 tryoig 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
