Given the links between mtDNA damage, splicing, ALS (MND) and PD, an obvious thing to look at is Multiple Sclerosis.
MS is a failure of the myelin sheaf. It has been thought to be as a result of an auto-immnue response, but an alternative perspective would be a failure of homeostasis. I thought I would ask chatGPT to look at both sides of the argument about splicing and this is the response:
chatGPT O3 response to question: "what are the arguments for and against multiple sclerosis resulting from aberrant splicing in the production of myelin"
The summary result from chatGPT is:
Bottom line
The case for aberrant splicing in myelin production as a contributor to MS is biologically plausible and experimentally supported, but the case against it being the primary cause remains strong.
At present, the weight of population genetics and virology favours a model in which immune dysregulation (often EBV-driven) comes first, with myelin-splice errors acting as modifiers or amplifiers rather than root causes. Future high-resolution genomics and antigen-presentation studies will be needed to settle whether a distinct “spliceopathy” endotype of MS truly exists.
Obviously that does not settle the issue and it raises some questions. However, treating MS as a splicing/mtDNA problem gives a number of potential interventions that it would be worth trying out.
MS is a failure of the myelin sheaf. It has been thought to be as a result of an auto-immnue response, but an alternative perspective would be a failure of homeostasis. I thought I would ask chatGPT to look at both sides of the argument about splicing and this is the response:
chatGPT O3 response to question: "what are the arguments for and against multiple sclerosis resulting from aberrant splicing in the production of myelin"
The summary result from chatGPT is:
Bottom line
The case for aberrant splicing in myelin production as a contributor to MS is biologically plausible and experimentally supported, but the case against it being the primary cause remains strong.
At present, the weight of population genetics and virology favours a model in which immune dysregulation (often EBV-driven) comes first, with myelin-splice errors acting as modifiers or amplifiers rather than root causes. Future high-resolution genomics and antigen-presentation studies will be needed to settle whether a distinct “spliceopathy” endotype of MS truly exists.
Obviously that does not settle the issue and it raises some questions. However, treating MS as a splicing/mtDNA problem gives a number of potential interventions that it would be worth trying out.
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