ALS (Amyotrophic Lateral Sclerosis) tends to be called MND (Motor Neuron Disease) in the UK. It is also known as Lou Gehrig's disease because he was a famous baseball player whose career was ended when he died of ALS in his 30s.
There are perhaps two main versions of ALS Familial (or inherited) and Sporadic which does not appear to be inherited. MND is perhaps a broader category which includes Progressive Muscular Atrophy (PMA), Primary Lateral Sclerosis (PLS) and Progressive Bulbar Palsy (PBP) as well as ALS. In this post I am going to concentrate on ALS. That is not to say that things I say in this post do not necessarily also apply to the other types of MND, but I have not looked at that question as yet.
I wrote a post a few weeks ago What causes Parkinson's Disease - is it actually an accelerated form of brain aging? and since then have been doing some experimentation with a small number of biohackers who have Parkinsons Disease.
The hypothesis is basically that the underlying cause of the symptoms of PD is accelerated damage to the mitochondria in certain brain cells. The reason for the Substantia Nigra being the area of the brain that is where the primary damage occurs is its proximity to the third ventricle of the Cerebrospinal Fluid and a reduction in melatonin flow from the pineal gland to the third ventricle. Melatonin as an anti-oxidant protects mitochondrial DNA from the damage normally caused by free radicals created by complexes 1 and 3 of the electron transport chain.
I recently read a tweet:
Which got me thinking about ALS, which is to be fair quite a nasty disease to have. Hence there are some simple questions to ask:
a) What evidence is there of mitochondrial damage which would result from a shortage of melatonin from CSF?
b) Is the phenotype linked to aberrant splicing (which would result from mitochondrial damage because that reduces citrate efflux from the mitochondria causing splicing changes)?
c) Is there potentially a connection to damaged CSF flow which would reduce melatonin supply to neurons below any blockage?
This is the point at which using an LLM becomes useful so I asked these questions of chatGPT. I have shared the questions and response and if you want to read it they are here: response to above three questions, slightly differently phrased.
I also separately asked about what the function of genes in familial CSF was and they were mainly around mitochondrial function (including autophagy) and splicing so that would be consistent.
In summary (and chatGPT does provide links to papers) the evidence is that ALS is associated with mitochondrial damage, aberrant splicing and disrupted CSF flow.
Now, of course, this has the status of a hypothesis that is not proven. However, it does give the option of experimenting with biohacking techniques to improve mitochondrial function and splicing. This would involve a mix of interventions. some to change splicing, some to fix mitochondrial via mitophagy and some to directly improve mitochondrial function. Hence if there are any people interested in experimenting with this with the support of their medical professionals they should contact me.
Edit 26/6/25 Can compressive thoracic cord lesions cause a pure lower motor neurone syndrome? gives substance to the argument about disrupted CSF flow.
"Abstract
Compressive lesions of the spinal cord usually cause a syndrome of upper motor neurone weakness, spasticity and sensory loss below the level of the lesion. It has long been recognised that compressive cervical cord lesions may present as isolated lower motor neurone weakness of the upper limbs, a syndrome termed cervical spondylotic amyotrophy. We describe two patients presenting with isolated lower motor neurone weakness of the lower limbs in association with a compressive cord lesion at T11/12, a condition we have termed thoracic spondylotic amyotrophy."
There are perhaps two main versions of ALS Familial (or inherited) and Sporadic which does not appear to be inherited. MND is perhaps a broader category which includes Progressive Muscular Atrophy (PMA), Primary Lateral Sclerosis (PLS) and Progressive Bulbar Palsy (PBP) as well as ALS. In this post I am going to concentrate on ALS. That is not to say that things I say in this post do not necessarily also apply to the other types of MND, but I have not looked at that question as yet.
I wrote a post a few weeks ago What causes Parkinson's Disease - is it actually an accelerated form of brain aging? and since then have been doing some experimentation with a small number of biohackers who have Parkinsons Disease.
The hypothesis is basically that the underlying cause of the symptoms of PD is accelerated damage to the mitochondria in certain brain cells. The reason for the Substantia Nigra being the area of the brain that is where the primary damage occurs is its proximity to the third ventricle of the Cerebrospinal Fluid and a reduction in melatonin flow from the pineal gland to the third ventricle. Melatonin as an anti-oxidant protects mitochondrial DNA from the damage normally caused by free radicals created by complexes 1 and 3 of the electron transport chain.
I recently read a tweet:
There’s no single reason ALS isn’t cured yet—but here are the key factors, plainly and painfully:
— Anthony Carbajal (@carbajalphoto) May 18, 2025
⸻
1. It’s Rare—So It’s Ignored.
ALS affects a relatively small population (about 30,000 in the U.S. at any time). That means less profit for pharmaceutical companies, and less…
Which got me thinking about ALS, which is to be fair quite a nasty disease to have. Hence there are some simple questions to ask:
a) What evidence is there of mitochondrial damage which would result from a shortage of melatonin from CSF?
b) Is the phenotype linked to aberrant splicing (which would result from mitochondrial damage because that reduces citrate efflux from the mitochondria causing splicing changes)?
c) Is there potentially a connection to damaged CSF flow which would reduce melatonin supply to neurons below any blockage?
This is the point at which using an LLM becomes useful so I asked these questions of chatGPT. I have shared the questions and response and if you want to read it they are here: response to above three questions, slightly differently phrased.
I also separately asked about what the function of genes in familial CSF was and they were mainly around mitochondrial function (including autophagy) and splicing so that would be consistent.
In summary (and chatGPT does provide links to papers) the evidence is that ALS is associated with mitochondrial damage, aberrant splicing and disrupted CSF flow.
Now, of course, this has the status of a hypothesis that is not proven. However, it does give the option of experimenting with biohacking techniques to improve mitochondrial function and splicing. This would involve a mix of interventions. some to change splicing, some to fix mitochondrial via mitophagy and some to directly improve mitochondrial function. Hence if there are any people interested in experimenting with this with the support of their medical professionals they should contact me.
Edit 26/6/25 Can compressive thoracic cord lesions cause a pure lower motor neurone syndrome? gives substance to the argument about disrupted CSF flow.
"Abstract
Compressive lesions of the spinal cord usually cause a syndrome of upper motor neurone weakness, spasticity and sensory loss below the level of the lesion. It has long been recognised that compressive cervical cord lesions may present as isolated lower motor neurone weakness of the upper limbs, a syndrome termed cervical spondylotic amyotrophy. We describe two patients presenting with isolated lower motor neurone weakness of the lower limbs in association with a compressive cord lesion at T11/12, a condition we have termed thoracic spondylotic amyotrophy."
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