Drug protects mice against malaria brain damage, raises levels of BDNF in humans

Cerebral malaria is a serious complication of infection with the malaria parasite, affecting approximately one in a thousand children in areas where malaria is common. Many of the patients die, and among those who survive, about a third have lasting cognitive and neurological disabilities, including epilepsy and learning disorders. A study published on March 6th in PLOS Pathogens shows that a known drug can prevent brain damage in a cerebral malaria mouse model and eliminate subsequent neurological deficits.

Infection with the elicits a strong immune response in the patient, and it is known that both parasite and host response contribute to the nervous system problems in . Lena Serghides, from the Toronto General Research Institute, Canada, and colleagues are interested in modulating the host response to , in addition to anti-parasite drugs, with the goal to improve outcomes in patients.

They focused on a drug called rosiglitazone (approved for patients with diabetes) which activates a molecule called PPARɣ and is known to have anti-inflammatory and anti-oxidant properties. Using a mouse model of cerebral malaria, they show that when they give rosiglitazone in addition to at the onset of cerebral malaria symptoms, mice are more likely to survive, and the survivors which had received rosiglitazone did not show the brain abnormalities or cognitive defects seen in surviving mice that had only received antimalarial drugs.

When they compared both groups of mice at the molecular level, they found that rosiglitazone protects the integrity of the blood-brain-barrier and increases the level of anti-oxidant enzymes and of neuroprotective factors in the brain. One of the latter, called BDNF (for brain-derived neurotropic factor), was also increased in the blood of adult human patients with uncomplicated malaria who had participated in a clinical trial and received antimalarial drugs plus rosiglitazone, compared with other trial participants who had only taken antimalarials.

"Our results demonstrate that rosiglitazone adjunctive therapy resulted in increased survival and protection from long-term cognitive impairments in a of cerebral malaria", the authors say, "And the clinical trial data suggests that this approved drug, which has an excellent safety profile when taken for limited periods, might also induce such putative protective mechanisms in humans". They conclude that "in view of these results, testing rosiglitazone in patients with cerebral malaria is warranted."

More information: dx.plos.org/10.1371/journal.ppat.1003980

add to favorites email to friend print save as pdf

Related Stories

Statin drug shows promise for fighting malaria effects

Dec 27, 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 ...

Potential new anti-malarial drug identified

Feb 06, 2014

A significant milestone in the development of a potential new antimalarial medicine has been reached by scientists at the University of Dundee, in partnership with the Medicines for Malaria Venture (MMV).

Recommended for you

Ebola kills 31 people in DR Congo: WHO

45 minutes ago

An outbreak of the Ebola virus in the Democratic Republic of Congo has killed 31 people and the epidemic remains contained in a remote northwestern region, UN the World Health Organization (WHO) said Tuesday.

Dengue fever strikes models in Japan

3 hours ago

A worsening outbreak of dengue fever in Japan has claimed its first celebrities—two young models sent on assignment to the Tokyo park believed to be its source.

Japanese researchers develop 30-minute Ebola test

3 hours ago

Japanese researchers said Tuesday they had developed a new method to detect the presence of the Ebola virus in 30 minutes, with technology that could allow doctors to quickly diagnose infection.

Senegal monitors contacts of 1st Ebola patient

15 hours ago

Senegalese authorities on Monday were monitoring everyone who was in contact with a student infected with Ebola who crossed into the country, and who has lost three family members to the disease.

Cerebral palsy may be hereditary

21 hours ago

Cerebral palsy is a neurological developmental disorder which follows an injury to the immature brain before, during or after birth. The resulting condition affects the child's ability to move and in some ...

User comments