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Increasingly, statins – common cholesterol lowering drugs – are being looked at for their inflammation-reducing properties in the treatment of other diseases.
Long time readers of this blog will recall that Dr. David Fedson - former Professor of Medicine at the University of Virginia School of Medicine and formerly Director of Medical Affairs, Aventis Pasteur MSD – has advocated research into the potential role of low-cost statins during an influenza pandemic (see Lancet: David Fedson On Statins For Pandemic Influenza).
For more on statins, and how they might be used against pandemic influenza, you may wish to revisit:
Study: Statins, Influenza, & Mortality
Another Study On Statins And Pneumonia
A couple of years ago we saw a video presentation at the 2010 ICAAC Conference called A Role for Statins in Infectious Disease? #ICAAC) (excerpt below).
Statins are well-known as a class of drugs that are used to help lower cholesterol but recent evidence suggests they might be good for more than your heart. They may play a role in preventing and treating certain bacterial infections including pneumonia and sepsis. Presenters at ICAAC discuss the latest research on the potential of these drugs.
- Reimar Thomsen, Aarhus University Hospital, Aalborg, Denmark
- Matthew Falagas, Alfa Institute of Biomedical Sciences, Athens, Greece
- Nasia Safdar, University of Wisconsin, Madison, WI, United States
These presenters suggest that statins may directly affect viruses and fungi, as well as help dampen the body’s inflammatory response. One study discussed found a 30% reduction in 30-day pneumonia mortality among patients already on statins.
The caveat being that much of the evidence for statins efficacy comes from in vitro studies, or observational studies that can sometimes be influenced by what is known as the `healthy user bias’.
Simply put, patients who are already on statins when they develop pneumonia, sepsis, or influenza may be more likely to have a healthy lifestyle than those not on statins, potentially skewing the results.
Still, the results to date have been intriguing, if not totally convincing.
Which brings us to a a new study, appearing in PloS Pathogens, that looks at the potential role of statins in the treatment of cerebral Malaria.
There were about 219 million cases of malaria in 2010 and an estimated 660 000 deaths. Africa is the most affected continent: about 90% of all malaria deaths occur there.
Between 2000 and 2010, malaria mortality rates fell by 26% around the world. In the WHO African Region the decrease was 33%. During this period, an estimated 1.1 million malaria deaths were averted globally, primarily as a result of a scale-up of interventions.
Rarely mentioned in all of these figures are the (often life-long) neurological sequelae that cerebral malaria may produce, particularly among children.
These may include blindness, epilepsy, decreased motor skills, hearing impairment, aphasia (loss of speech), and behavioral problems, as noted in the following BMC Research Note.
Severe neurological sequelae and behaviour problems after cerebral malaria in Ugandan children
Richard Idro, Angelina Kakooza-Mwesige, Stephen Balyejjussa, Grace Mirembe, Christine Mugasha, Joshua Tugumisirize and Justus Byarugaba
Conclusions
In addition to previously described neurological and cognitive sequelae, severe behaviour problems may follow cerebral malaria in children. The observed differences in patterns of sequelae may be due to different pathogenic mechanisms, brain regions affected or extent of injury. Cerebral malaria may be used as a new model to study the pathogenesis of ADHD.
The PloS Pathogens study, which looks at the potential use of statins for cerebral malaria in a murine (mouse) model, involved infecting lab mice with the malaria parasite, and then treating half of them with just chloroquine, and the other half with chloroquine and Lovastatin.
Mice that received the combination treatment saw a significantly reduced rate of post-infection cognitive dysfunction.
Statins Decrease Neuroinflammation and Prevent Cognitive Impairment after Cerebral Malaria
Patricia A. Reis mail, Vanessa Estato, Tathiany I. da Silva, Joana C. d'Avila, Luciana D. Siqueira, Edson F. Assis, Patricia T. Bozza, Fernando A. Bozza, Eduardo V. Tibiriça, Guy A. Zimmerman, Hugo C. Castro-Faria-Neto
Author Summary
Cerebral malaria (CM) is the direst consequence of Plasmodium falciparum infection. Cognitive impairment is a common sequela in children surviving CM. Identification of adjunctive therapies that reduce the complications of CM in survivors is a priority. Statins have been suggested for the treatment of neuroinflammatory disorders due to their pleiotropic effects.
Here, we examined the effects of lovastatin on neuroinflammation in experimental CM, and its effect on the prevention of cognitive impairment. Lovastatin reduced adhesion and rolling of leukocytes in brain vessels, inhibited blood-brain barrier disruption, and reversed decreases in cerebral capillary density. Lovastatin also inhibited ICAM-1 and CD11b mRNA expression while increasing HMOX-1 mRNA levels. Proinflammatory cytokines and markers of oxidative stress were lower in the brains of infected mice treated with lovastatin.
Lovastatin administered together with antimalarial drugs during the acute phase of the disease-protected survivors from impairment in both contextual and aversive memory 15 days after infection. Similar results were observed in a model of bacterial sepsis.
Our findings support the possibility that statins may be valuable pharmacologic tools in treatment of patients with neuroinflammation associated with severe systemic inflammatory syndromes. Clinical trials with statins in CM and sepsis should be speedily considered to examine this point.
Of course, what works in mice isn’t guaranteed to work in humans. The authors caution:
These models may provide important insights into the pathogenesis of cognitive dysfunction associated with cerebral malaria and related disorders that may be relevant to human conditions [7]. While differences between murine models of CM and the human syndrome are often emphasized [10], [11], there are also important similarities [3], [7], [12]–[14]. Nevertheless, caution must be exerted when translating experimental findings to the clinical scenario.
The VOA has a nice write up of this study (see Mice Study Indicates Cholesterol Drug Might Help Treat Serious Malaria Cases), including an interview with one of the authors, who recommends that:
Zimmerman recommends lovastatin be added to treatments for malaria as well as for sepsis, a systemic blood infection commonly known as blood poisoning that sickens and threatens the lives of more people worldwide than cerebral malaria.
The problem with statins is that these are are cheap, generic drugs. They provide little financial incentive for their manufacturers to mount expensive human trials in order to prove their effectiveness against malaria, pneumonia, sepsis, or influenza.
So, while the evidence continues to suggest benefits to using statins for `off label’ purposes, real proof of their effectiveness may be a long time in coming.
