New molecular target identified for treating cerebral malaria

January 30, 2015

Boston, MA - A drug already approved for treating other diseases may be useful as a treatment for cerebral malaria, according to researchers at Harvard T. H. Chan School of Public Health. They discovered a novel link between food intake during the early stages of infection and the outcome of the disease, identifying two molecular pathways that could serve as new targets for treatment.

"We have known for a long time that nutrition can affect the course of infectious disease, but we were surprised at how rapidly a mild reduction in food intake could improve outcome in a mouse malaria model," said senior author James Mitchell, associate professor of genetics and complex diseases. "However, the real importance of this work is the identification of unexpected molecular pathways underlying cerebral malaria that we can now target with existing drugs."

The study appears online January 30, 2015 in Nature Communications.

Cerebral malaria -- a severe form of the disease -- is the most serious consequence of infection by the parasite Plasmodium falciparum, resulting in seizures, coma, and death. Currently there is a lack of safe treatment options for cerebral malaria, particularly for use in children, who represent the majority of cases. Even patients who receive early treatment with standard antimalarial chemotherapeutic agents run a high risk of dying, despite clearance of the parasite. Moreover, around 25% of survivors develop neurological complications and cognitive impairment.

Lead authors Pedro Mejia and J. Humberto Treviño-Villarreal, both researchers at Harvard T.H. Chan School of Public Health, found that leptin--a hormone secreted from fat tissue with roles in suppressing appetite, but also in activating adaptive immune and inflammatory responses--is increased upon infection in a mouse model of cerebral malaria, and turns out to be a major bad actor in promoting neurological symptoms and death. Remarkably, Mejia, Treviño-Villarreal and colleagues showed that reducing leptin using a variety of means, either genetically, pharmacologically, or nutritionally by reducing food intake during the first two days of infection, protected against cerebral malaria.

The researchers also found that leptin acted primarily on cytotoxic T cells by turning on the well-studied mTOR protein, for which pharmacologic inhibitors are readily available. In their animal model, treating mice with the mTOR inhibitor rapamycin protected them against the neurological complications of cerebral malaria. Protection was due in part to a preservation of the blood brain barrier, which prevented the entry of blood cells carrying the parasites into the brain. As rapamycin is already FDA-approved for use in humans, trials in humans for cerebral malaria treatment with this drug may be possible, according to the researchers.
-end-
This study was the result of an ongoing collaboration between the Mitchell lab in the Department of Genetics and Complex Diseases and the labs of Manoj Duraisingh and Dyann Wirth in the Department of Immunology and Infectious Diseases. Other Harvard T.H. Chan School of Public Health authors included Christopher Hine, Eylul Harputlugil, Samantha Lang, Ediz Calay and Rick Rogers.

This study was supported in part by grants from NIH (DK090629 and AG036712) and the Glenn Foundation for Medical Research to J.R.M.; a Harvard T.H. Chan School of Public Health Yerby postdoctoral fellowship to Mejia, and financial support from the Universidad Auto´noma de Nuevo Leo´n to Treviño-Villarreal.

"Dietary restriction protects against experimental cerebral malaria via leptin modulation and T-cell mTORC1 suppression," Pedro Mejia, J. Humberto Treviño -Villarreal, Christopher Hine, Eylul Harputlugil, Samantha Lang, Ediz Calay, Rick Rogers, Dyann Wirth, Manoj Duraisingh, and James R. Mitchell, Nature Communications, online January 30, 2015, 6:6050 doi: 10.1038/ncomms7050 (2014).

Visit the Harvard Chan website for the latest news, press releases, and multimedia offerings.

Harvard T.H. Chan School of Public Health brings together dedicated experts from many disciplines to educate new generations of global health leaders and produce powerful ideas that improve the lives and health of people everywhere. As a community of leading scientists, educators, and students, we work together to take innovative ideas from the laboratory to people's lives--not only making scientific breakthroughs, but also working to change individual behaviors, public policies, and health care practices. Each year, more than 400 faculty members at Harvard Chan teach 1,000-plus full-time students from around the world and train thousands more through online and executive education courses. Founded in 1913 as the Harvard-MIT School of Health Officers, the School is recognized as America's oldest professional training program in public health.

Harvard T.H. Chan School of Public Health

Related Public Health Articles from Brightsurf:

COVID-19 and the decolonization of Indigenous public health
Indigenous self-determination, leadership and knowledge have helped protect Indigenous communities in Canada during the coronavirus disease 2019 (COVID-19) pandemic, and these principles should be incorporated into public health in future, argue the authors of a commentary in CMAJ (Canadian Medical Association Journal) http://www.cmaj.ca/lookup/doi/10.1503/cmaj.200852.

Public health consequences of policing homelessness
In a new study examining homelessness, researchers find that policy such a lifestyle has massive public health implications, making sleeping on the street even MORE unhealthy.

Electronic health information exchange improves public health disease reporting
Disease tracking is an important area of focus for health departments in the midst of the COVID-19 pandemic.

Pandemic likely to cause long-term health problems, Yale School of Public Health finds
The coronavirus pandemic's life-altering effects are likely to result in lasting physical and mental health consequences for many people--particularly those from vulnerable populations--a new study led by the Yale School of Public Health finds.

The Lancet Public Health: US modelling study estimates impact of school closures for COVID-19 on US health-care workforce and associated mortality
US policymakers considering physical distancing measures to slow the spread of COVID-19 face a difficult trade-off between closing schools to reduce transmission and new cases, and potential health-care worker absenteeism due to additional childcare needs that could ultimately increase mortality from COVID-19, according to new modelling research published in The Lancet Public Health journal.

The Lancet Public Health: Access to identification documents reflecting gender identity may improve trans mental health
Results from a survey of over 20,000 American trans adults suggest that having access to identification documents which reflect their identified gender helps to improve their mental health and may reduce suicidal thoughts, according to a study published in The Lancet Public Health journal.

The Lancet Public Health: Study estimates mental health impact of welfare reform, Universal Credit, in Great Britain
The 2013 Universal Credit welfare reform appears to have led to an increase in the prevalence of psychological distress among unemployed recipients, according to a nationally representative study following more than 52,000 working-age individuals from England, Wales, and Scotland over nine years between 2009-2018, published as part of an issue of The Lancet Public Health journal on income and health.

BU researchers: Pornography is not a 'public health crisis'
Researchers from the Boston University School of Public Health (BUSPH) have written an editorial in the American Journal of Public Health special February issue arguing against the claim that pornography is a public health crisis, and explaining why such a claim actually endangers the health of the public.

The Lancet Public Health: Ageism linked to poorer health in older people in England
Ageism may be linked with poorer health in older people in England, according to an observational study of over 7,500 people aged over 50 published in The Lancet Public Health journal.

Study: Public transportation use linked to better public health
Promoting robust public transportation systems may come with a bonus for public health -- lower obesity rates.

Read More: Public Health News and Public Health Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.