Feature | December 28, 2012

Cholesterol Drug Shows Promise in Fighting Malaria

Statin therapy may decrease brain inflammation, prevent mental deterioration associated with severe malaria

December 28, 2012 — Researchers have discovered that adding lovastatin, a widely used cholesterol-lowering drug, to traditional antimalarial treatment decreases neuroinflammation and protects against cognitive impairment in a mouse model of cerebral malaria. Although there are differences between mouse models of cerebral malaria and human disease, these new findings indicate that statins are worthy of consideration in clinical trials of cerebral malaria, according to an article published in the Dec. 27 issue of PLOS Pathogens.

Malaria, a parasitic infection that is transmitted to humans by the female Anopheles mosquito, is one of the leading infectious diseases worldwide. Cerebral malaria is a severe, potentially fatal neurologic complication of infection by the parasite plasmodium falciparum. Studies of children with cerebral malaria show that cognitive deficits, such as impaired memory, learning, language, and mathematical abilities, persist in many survivors long after the infection itself is cured.

“Over 500,000 children develop cerebral malaria each year in sub-Saharan Africa, and persistent cognitive dysfunction in survivors is not only a major public health concern, but also a significant socioeconomic burden,” says Guy Zimmerman M.D., associate chair for research in the Department of Medicine at the University of Utah and senior co-author on the study. “There is an urgent and unmet medical need for therapies that treat or prevent cognitive impairment in cerebral malaria.”

Statins, a class of drugs best known for their ability to lower cholesterol, have also been shown to be active in modulating a variety of immune system responses. In their research, Zimmerman and his Brazilian colleagues evaluated the effect of statins in a mouse model of cerebral malaria. The researchers found that adding a drug called lovastatin to traditional antimalarial therapy prevented cognitive dysfunction in mice infected with cerebral malaria. They discovered that addition of lovastatin decreased white blood cell accumulation and leakiness in blood vessels in the brain. Lovastatin also reduced production of damaging oxygen-containing molecules and other factors that promote inflammation.

“The molecular mechanisms that give rise to cerebral malaria and subsequent cognitive dysfunction are not yet known,” says Zimmerman. “However, the fact that statin treatment decreases both injurious blood vessel inflammation and cognitive dysfunction suggests that a combination of vascular and inflammatory triggers leads to cerebral pathology and intellectual deficits.”

Zimmerman and his colleagues also studied lovastatin in an experimental model of bacterial sepsis, a severe whole-body inflammatory state that can also lead to cognitive impairment. They found that lovastatin also prevented cognitive impairment after bacterial sepsis.

“Our findings are exciting because the clinical implications extend beyond cerebral malaria to other severe systemic inflammatory syndromes complicated by brain involvement,” said Zimmerman. “We believe our observations are the first experimental evidence to support the possibility of using statins to reduce cognitive impairment in critically ill patients.”

This study is the latest result of a long-term collaboration between Zimmerman and Dr. Hugo Castro-Faria-Neto and his group at the Oswaldo Cruz Foundation, a Brazilian research institute dedicated to the study, prevention, and treatment of infectious diseases. This collaboration began when Dr. Castro-Faria-Neto was a visiting scientist at the University of Utah. Future research will focus on additional investigation into the molecular mechanisms of cerebral malaria and the responses of key immune cells to malaria toxins, as well as on studies of the systemic inflammatory component of malaria in human patients.

 

Related Content

DEFUSE-2 study, MRI, brain bleeding risk, post-stroke treatment, NIH

This image combines pre- and post-treatment scans from the same patient. Analysis of the two scans revealed that the area and size of post-treatment bleeding corresponded to blood-brain barrier disruption (shown in green, yellow and red) prior to therapy. Image courtesy of Richard Leigh, NINDS.

News | Stroke| June 29, 2016
In a study of stroke patients, investigators confirmed through magnetic resonance imaging (MRI) brain scans an...
U.K., NHS studies, weekend effect, hospital admission, atrial fibrillation, heart failure
News | Clinical Study| June 28, 2016
New research shows patients admitted to National Health Service (NHS) hospitals in the United Kingdom for atrial...
CT scans, cancer risk, radiation dose, Canadian study
News | Computed Tomography (CT)| June 27, 2016
June 27, 2016 — A new study in the Journal of Medical Imaging and Radiation Sciences surveyed doctors, radiologists a
atrial fibrillation, stroke risk, aspirin vs blood thinners, JACC study
News | Antiplatelet and Anticoagulation Therapies| June 24, 2016
More than 1 in 3 atrial fibrillation (AF) patients at intermediate to high risk for stroke are treated with aspirin...
News | Cardiac Diagnostics| June 24, 2016
Measuring antibody levels in the blood could be used to detect a person’s heart attack risk after researchers, part-...
Zoll LifeVest wearable defibrillator, WEARIT-II Registry results, CardioStim EuroPace 2016
News | Defibrillator Monitors| June 21, 2016
Zoll Medical Corp. announced that patients experience a high one-year survival rate following use of the LifeVest...
News | Implantable Cardioverter Defibrillators (ICD)| June 14, 2016
Medtronic plc announced results from several feasibility studies evaluating a new approach to implantable cardioverter...
hypertrophic cardiomyopathy, HCM, strain echocardiography, risk assessment, ASE 2016
News | Cardiovascular Ultrasound| June 13, 2016
After following a large sub-set of patients, researchers found that by using strain echocardiography they could...
ASE 2016, Mayo Clinic study, echocardiography, aortic flow rate, patient risk stratification
News | Cardiovascular Ultrasound| June 13, 2016
Researchers from Mayo Clinic believe they have found a better way to risk stratify some of their most fragile patients.
hemmorhagic stroke, blood pressure management, ATACH II trial, NINDS

Brain scan showing damage caused by bleeding during a hemorrhagic stroke. Image courtesy of Adnan I Qureshi, M.D., University of Minnesota.

News | Stroke| June 09, 2016
June 9, 2016 — An international stroke study
Overlay Init