What does this have to do with Parkinson's? There has been interest on this forum in increasing activation of the Nrf2 pathway as a way to reduce oxidative stress & inflammation in the brain.
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On February 28th 2023, the U.S. Food and Drug Administration approved SKYCLARYS, the first drug ever to treat Friedreich’s ataxia.
Friedreich’s ataxia is a neurodegenerative movement disorder so this is interesting.
"SKYCLARYS became the first ever approved drug to show a positive result in slowing the progression of Friedrich’s ataxia."
"Skyclarys contains omaveloxolone, an activator of the nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway, which is suppressed in people with Friedreich’s ataxia."
"Interestingly, Nrf2 signaling pathway has shown upregulation of antioxidant genes, inhibition of microglia-mediated inflammation, and improved mitochondrial function in neurodegenerative diseases, suggesting Nrf2 activation could be a novel therapeutic approach to target pathogenesis."
"Nrf2 activators mechanism of action make them a viable option in the treatment of many diseases associated with oxidative stress in addition to FRDA, including several neurodegenerative diseases. Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s Disease (PD), Multiple Sclerosis (MS) and Amyotrophic Lateral Sclerosis (ALS) have all been linked to abnormalities in the Nrf2 pathway.22"
They will be doing long term follow up on ppl taking it for Friedrich's - so we'll find out eventually. Risk/benefit is likely worth it in FA. Risk for heart problems will probably be greater for older ppl. It's possible negative effects on heart could be mitigated with use of another drug such as low dose rapamycin or a statin* or maybe just arginine supplementation or exercise.
So it sounds like it has benefits so I was kind of surprised to see the research that I found and I find it frustrating when you see several articles focused on benefits of a medication then sometimes you see that maybe for some people it might not work well just because of having more than one medical problem at the same time.
I can't think of any drug or biological pathway where it doesn't have a context in which it could have a harmful effect. There are unfortunately going to be patients in which they have 2 or more things going on - particularly in the elderly. My father had MSA and also had a lesion in his lung which was probably cancerous. They didn't biopsy since he was near the near of his life . At present it would be hard to treat both MSA & cancer at the same time since for neurodegenerative diseases you want to prevent cell death & in cancer you want to promote it.
But biotechnology is progressing rapidly & developments in AI are accelerating it even more - so I expect there will be solutions to such conundrums in the not-so-distant future.
FA is caused by genetic mutations that lead to low levels of frataxin, a protein that’s necessary for the functioning of mitochondria, which serve as the energy production centers of cells.
In FA, mitochondrial dysfunction and impairments in cellular energy production drive chronic inflammation and vulnerability to oxidative stress, a type of cell damage. Oxidative stress is marked by an imbalance between the production of toxic reactive oxygen species and the antioxidant defenses needed to clear them. As a consequence, patients experience progressive neurodegeneration and a loss of muscle strength and coordination.
Skyclarys is designed to activate nuclear factor erythroid 2-related factor 2 (NrF2), a type of protein called a transcription factor whose signaling is impaired in FA patients. NrF2 works to activate genes that promote mitochondrial function, boost antioxidant responses, and prevent inflammation.
In doing so, the therapy is expected to slow or prevent disease progression in people with FA.
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