Hydroxychloroquine

[Dixie1973]

Has anyone tried hydroxychloroquine it’s prescribed for the treatment or prevention of malaria.

Article publised online in April 2021 Metabolic rerouting via SCD1 induction impacts X-linked adrenoleukodystrophy.

We found that activation of SCD1 caused a shift in the synthesis of saturated VLCFAs toward monounsaturated VLCFAs, decreasing levels of saturated VLCFAs in ALD human fibroblasts and mouse tissues. These results indicate that saturated VLCFAs mediate key disease pathology in ALD and suggest that metabolic rerouting toward the monounsaturated fatty acids may open a new option toward a therapy for ALD and other peroxisomal disorders.

Chloroquine increased expression of stearoyl-CoA desaturase-1 (scd1), the enzyme mediating fatty acid saturation status, suggesting that a shift toward monounsaturated fatty acids relieved toxicity. In human ALD fibroblasts, chloroquine also increased SCD1 levels and reduced saturated VLCFAs.

pubmed.ncbi.nlm.nih.gov/336...

[cfox]

That's a very interesting study. It sounds like they are now able to screen lots of potential drugs quickly using ALD zebrafish, which is way faster and cheaper than using mice. This is a very promising tool for drug discovery in ALD/AMN, and will hopefully speed up development of treatments.

But it doesn't sound like they are proposing chloroquine itself (or hydroxycloroquine) as a potential treatment. They are saying it's toxic when taken long-term, and to be of any use to us as a treatment it would have to be taken for many years:

"Although promising, pursuit of chloroquine or of LXR agonists as potential treatments for AMN has notable limitations and was not a primary purpose of this work. Treatment for AMN may need to be initiated during adolescence or even earlier to be of maximal benefit, and thus any exposure to a compound will be for multiple decades. Chloroquine or hydroxychloroquine, a metabolite of chloroquine, has a narrow therapeutic window, causes retinal toxicity in as many as 20% of patients, and has been associated with serious cardiac complications, including arrhythmias, cardiomyopathy, and death. Currently available LXR agonists have significant side effects, including in particular hepatic steatosis and hypertriglyceridemia, and have not been approved for clinical use."

I would be surprised if any doctor would endorse taking this drug off-label, mostly because of the toxicity but also because you would essentially be guessing at an appropriate dose (and they point out that chloroquine has a "narrow therapeutic window").

[Dixie1973 in reply to cfox]

Hydroxychloroquine is a derivative of chloroquine phosphate that has been demonstrated to be 40% less toxic than chloroquine, I think most drugs are toxic it’s a matter of dose.

Hydroxychloroquine sold under the brand name Plaquenil is also prescribed for lupus erythematosus and rheumatoid arthritis, … and it was a hype for Covid-19.

My mom takes it for lupus with no side effects only annual test at the ophthalmologist.

Problem find a doctor who want to prescribe it off label.

[monkeybus]

I am always on the lookout for old, established drugs that might be repurposed to help us. As soon as Trump started hyping this drug (at one point claiming to be taking it every day), I Googled it to see if it had any benefits for us, saw the toxicity, then forgot all about it.

Even tonic water hardly contains any quinnine these days, so toxic is it.

It is yet another good start though.