David Shuey
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David Shuey
MemberAugust 11, 2023 at 10:01 am in reply to: Which ALS-related science, research, etc. topic is on your radar right now?I am following the first large clinical trial of an NAD+ elevating supplement – nicotinamide riboside. This trial of 380 participants was initiated in 2020 in Norway and results are expected later this year. A small pilot study published in 2019 was very encouraging, as selected patients demonstrated significant responses to this treatment.
Clinical trial (ongoing): https://www.clinicaltrials.gov/study/NCT04562831
Pilot study: https://www.tandfonline.com/eprint/5j6sIsrMDYd37hjpNghx/full
Following the 2019 study and after discussions with the scientists involved, we started my wife on “Basis” (nicotinamide riboside + pterostilbene). She has been taking it for 5 years now and her progression has essentially stopped. I realize this is anecdotal, but for some patients it is theoretically possible, if the causative defect of the neurodegeneration was indeed related to low NAD+. Ceratain SARM1 mutations (below) would fall into this class. We are currently having my wife’s exome sequenced to see if anything interesting pops up.
SARM1 and ALS: https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-021-00511-x -
“Simply put, the drug wraps itself around the mutated gene and fills in the miscoded instructions. The gene then is able to produce the SOD1 proteins correctly.” – Amanda
This is not likely what’s happening here. These drugs are known as ASO’s (anti-sense oligonucleotides). As the name implies, they small strands of nucleotides with essentially the complimentary sequence to the mRNA. They form a duplex RNA hybrid that is digested by cellular nucleases, thus repressing SOD1 expression.
So why do you want to inhibit mutant SOD1 gene expression? It is thought that the mutant forms of SOD1 actually self assemble to form neurotoxic protein aggregates. Such proteinopathies, as they are known, are found in many neurodegenerative diseases.
Hope this helps … Dave
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David Shuey
MemberFebruary 5, 2021 at 10:01 am in reply to: New study shows ALS/MND damage to nerve cells can be repaired by improving the energy levels in mitochondriaFYI – Several excellent threads at the ALS-TDI Forums (https://www.als.net/forum/) discuss the link between mitochondrial health and ALS pathologies and suggest a number of potential therapeutic strategies.
The most comprehensive is clearly the discussion started back in 2014 by an excellent contributor Barbarawanda titled – Quality control of mitochondria in neurons
Other more recent threads include:
Melatonin is produced in the mitochondria and that may be for a good reason…….
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On a personal note, my wife is in her 12th year of Bulbar-onset ALS. For a number of reasons, we are very big believers in NAD+ elevation strategies – not only for promoting mitochondrial and metabolic health, but also its critical role as a sirtuin cofactor. For this, we also use pterostilbene as a sirtuin co-activator (think resveratrol). I suggest that melatonin supplementation should also be considered.
Reviewed: “NAD+ in brain aging and neurodegenerative disorders” https://pubmed.ncbi.nlm.nih.gov/31577933/
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A pilot study of the NAD+ precursor Nicotinamide Riboside + pterostilbene conducted in Spain in 2017 was very promising: (https://www.tandfonline.com/eprint/5j6sIsrMDYd37hjpNghx/full?target=10.1080%2F21678421.2018.1536152&😉
A Phase 2 equivalent trial is currently recruiting in Norway: ClinicalTrials.gov Identifier: NCT04562831
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Cheers and Good Luck to all ~ Dave