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Science, Medicine, Technology
  Deb Pal
Decoding epilepsy

Columbia scientists say they’ve found a genetic link to rolandic epilepsy, a childhood seizure disorder that causes the face, mouth, and throat to go numb, sometimes for an hour or more.

The scientists, led by Columbia pediatric neurologist Deb Pal, analyzed DNA samples from 194 children with rolandic epilepsy, from their family members, and from a control group. The researchers concluded that mutations of the gene ELP4 are strongly associated with rolandic epilepsy, a common disorder whose genetic basis, until now, was a mystery. Scientists already knew that ELP4 creates proteins that are necessary for building neuronal networks in early childhood. They also suspected that if this gene was expressed improperly, the brain’s electrical wiring could turn out faulty. But the Columbia study is the first to link ELP4 to a specific disease; the paper appeared in the February issue of the European Journal of Human Genetics.

According to Pal, this discovery is just the first step in understanding rolandic epilepsy, which probably results from the malfunctioning of dozens of genes. As more genes are identified as part of the pathology, Pal says, better diagnostic tools and treatments may be developed. He points out that, today, antiepileptic drugs are blunt instruments; scientists know little about what causes epilepsy, so they treat it with chemicals that dampen electrical activity throughout the entire brain, often with unintended consequences. Drugs for rolandic epilepsy can have serious side effects, including hyperactivity and sleeplessness.

“If we knew the actual causes of this disorder at the genetic level, then we could develop treatments that target the specific genetic pathways at work,” says Pal. “This finding hopefully will help lead us to the right intervention.”

Rolandic epilepsy affects about 15 percent of children who have epilepsy and typically disappears in late adolescence. Pal suspects that it isn’t the only disorder that stems from a mutation of the ELP4 gene. In fact, his research team identified ELP4 by working backward from a type of abnormal electrical activity, called centrotemporal spikes (CTS), that they had observed in the brains of children with rolandic epilepsy as well as in the brains of their relatives with other types of epilepsy or with developmental problems, such as attention-deficit/hyperactivity disorder and speech dyspraxia. Pal hypothesizes that ELP4 plays a key role in causing CTS and that other genes then determine whether a full-blown neurological disorder results, and if so, which one.

“On top of CTS, there have to be other factors that tip you over the edge from brain-wave abnormality to seizures,” says Pal. “There are a lot more genes we still need to find.”

Other authors of the study include Columbia epidemiologists Bhavna Bali, Peregrine L. Murphy, and Tara Clarke; Columbia geneticist David A. Greenberg; former Columbia geneticist Lisa Strug; and researchers at Penn and Brown.

SIPA student Mari Denby teaches health workers to text message in Malawi.
Somebody text a doctor

A group of Columbia students is using mobile phones to improve the collection of health-care data in Malawi, where laborious paper forms make it difficult for health workers to submit field data to government officials. Health workers have found that mobile-phone text messages can transmit data quickly and accurately, thereby allowing them to better care for their patients and respond to health emergencies, such as famines.

“A lot of the information that’s written down is inaccurate and takes between three months to a year to reach the central government level,” said Mari Denby, a graduate student who is working on child nutrition surveillance in Malawi with five of her peers from the School of International and Public Affairs (SIPA). The group is enrolled in SIPA’s development practice workshop, which pairs groups of students with clients to work on a specific project.

Through the workshop, Denby and her classmates — Kirsten Bokenkamp, Roxana Cosmaciuc, Sean Blaschke, Beza Hailu, and Ray Short — are collaborating with client UNICEF to develop and deploy an open-source “RapidSMS,” or short message service system, which distributes mobile phones to health workers so they can instantly communicate data on child nutrition. This will allow UNICEF, the government of Malawi, and other partners to accurately map and track child nutrition trends. The students’ project won the U.S. Agency for International Development’s first Development 2.0 Challenge in January, which included a $10,000 grant.

In early 2009, several students visited Malawi to help set up the system and to train health workers to use it. Now the students are monitoring their system and advocating for better data transmission in Malawi.

UNICEF representative Christopher Fabian described the collaboration with SIPA as “a new type of partnership for UNICEF” that is generating excitement within the organization. “We’re happy to extend this. I think we can do a whole lot of interesting things next year.”

  HIV virus particles are shown here, in red and orange, budding from the surface of a T4 lymphocyte cell, whose own cellular machinery has been hijacked to make more copies of HIV.
Putting HIV prevention in women’s hands

A clinical trial involving more than 3000 women in the United States and southern Africa has demonstrated for the first time that an antiviral gel applied topically could prevent male-to-female HIV transmission. An international team of researchers led by Columbia epidemiologist Salim S. Abdool Karim found that women who agreed to use a microbicide gel were 30 percent less likely to contract HIV over the course of the 20-month study, which took place between February 2005 and September 2008. The findings were presented in February at the Conference on Retroviruses and Opportunistic Infections in Montreal.

Several types of microbicide gels have been tested previously in clinical trials but have yielded less-promising results, says Karim, who is a professor at the Mailman School of Public Health, vice-chancellor for research at the University of KwaZulu-Natal in Durban, South Africa, and director of the Centre for the AIDS Programme of Research in South Africa.

The gel that was found to be effective is known as PRO 2000 and is made by Indevus Pharmaceuticals Inc. in Lexington, Massachusetts. It is designed to inhibit HIV’s entry into cells in the genital tract. The group also tested a microbicide gel called BufferGel, which increases the vagina’s natural acidity, but found that it did not effectively prevent transmission.

“Although more data are needed to conclusively determine whether PRO 2000 protects women from HIV infection, the results of this study are encouraging,” says Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, which funded part of the study.

All of the study participants received detailed information about the possible risks and benefits of trial participation and were counseled on safe-sex practices, given condoms, and tested and treated for sexually transmitted infections throughout the study.

Developing an effective microbicide gel is important for women, researchers say, because women often cannot negotiate condom use with their male partners. “The study provides a glimmer of hope to millions of women at risk for HIV,” says Karim, “especially young women in Africa.”


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