Old friends, new enemies
Chloroquine is an old friend for humans. Together with other related compounds, it has been extracted from the quina-quina tree since 400 years ago to treat malaria. Like it or not, malaria was a huge problem until only 100 years ago in many parts of the world, so when the synthetic Chloroquine was discovered in 1934, it boomed in popularity for malaria treatment 1.
While the further development of this drug kept going (like the synthesis of Hydroxychloroquine and other modified variants), like it happens many times in nature, chloroquine-resistant strains became widespread, and it led to an almost complete stop to the use of chloroquine in malaria treatment, at least as a single-shot solution 1.
This does not mean that Chloroquine was abandoned, but instead was repurposed as a complementary malaria treatment and its systemic actions were explored in treatments for immune conditions such as rheumatoid arthritis 2 and lupus 3. More recently, Chloroquine and Hydroxychloroquine were even used as antiviral against many viruses, including HIV, SARS and avian influenza 4.
As the well-known COVID pandemic hit the world, a great deal of debate emerged and rushed researches considered the use of Chloroquine for the treatment of the SARS-CoV-2 virus as well. As many already know, it led to complicate political discussions before revealing itself not so useful and sometimes, dangerously hazardous 5.
Old friends don’t always have known faces
Don’t take me wrong, I mean neither to contribute to the chloroquine-for-COVID debate nor to question its usefulness for other applications. The important aspect that I want to discuss here, which in my opinion is not often mentioned, is that we actually don’t really know how Chloroquine works. Let me explain.
One would expect that for an almost 100 years old drug, we would know the ins and outs of its properties, mechanisms and functions. But, pay attention, this is clearly not the case! It’s actually very important to realize that often, something gets used just because it works, even if we still don’t fully know why it works!
How does it work in Malaria?
Even if we used Chloroquine and derivatives for malaria treatment for ages, the mechanisms for which the malaria parasite actually is affected by the drugs is not well understood! It might have to do with Heme interaction? Maybe vacuole membrane disruption? Maybe with its interaction with the DNA at high concentration? It could be simply due to the systemic effects of Chloroquine onto our immunite system 6.
How does it work in antiviral therapy?
In its more recent uses for HIV and other virus therapy, the confusion is even larger: is it simply blocking of DNA replication or RNA expression? Is it the reduced glycosylation of certain receptors 4? Is it simply inhibition of the immune reaction due to the viral infection 7? Perhaps a pH effect on the virus replication cycle 8?
How does it work for autoimmune diseases?
Conditions like lupus and rheumatoid arthritis are autoimmune complicated conditions of which the “normal” biology is poorly understood. It is not surprising that the effect of Chloroquine into these complicated systems increases this uncertainty. Here, more than just knowing that it has effect on our immune response and the regulation of our immune cells, we know little else 2-3.
The devil is in the details
When you dig deep, and you look at how science, biology and medicine works, you often realize how far we still are in understanding basic concepts and phenomena that we have been studying for years. This is not a bad thing, it’s simply the reality of the complexity of our world and universe.
When one keeps this simple concept in mind, it becomes so easy to understand why one cure-all solutions and poorly researched and cheap options are likely not to solve complex problems in science. Keep this in mind when you read my next story…
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