Investigators will study how environmental risk factors like a folic acid deficiency increase risk for spina bifida and related congenital defects.

NEW YORK (Sept. 26, 2011) — The National Institutes of Health (NIH) has awarded a five-year, $5.5 million Transformative Research Project (T-R01) Award to fund research into risk factors for spina bifida and related congenital defects in which an area of the affected baby's spine or brain is not fully enclosed.

The research will be led by Dr. Margaret Elizabeth Ross and Dr. Christopher E. Mason at Weill Cornell Medical College. Dr. Ross is the director of the Laboratory of Neurogenetics and Development and professor and vice chair for research in the Department of Neurology and Neuroscience, and Dr. Mason is an assistant professor of computational genomics in the Department of Physiology and Biophysics and at the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine. They will work in collaboration with Dr. Richard H. Finnell of the University of Texas at Austin.

The award to Dr. Ross and Dr. Mason is among 79 awards totaling $143.8 million that were recently announced by the NIH. It is also one of only 17 given in the transformative research category in 2011. According to the NIH: "The Common Fund's NIH Director's Transformative Research Award initiative, formerly known as the Transformative Research Project (TR01), is created specifically to support exceptionally innovative and/or unconventional research projects that have the potential to create or overturn fundamental paradigms."

Spina bifida and other serious neural tube defects (NTDs) develop from a complex interaction between genetic and environmental factors in which the environment influences how the fetus' genetic blueprint is read during development. One critical influence is the addition of methyl groups to DNA that can make it less likely that the modified, methylated gene will be used to make the protein it encodes. The Weill Cornell study seeks to identify which among all the genes in the cell are modified by folic acid levels, and how those patterns can be used to assess individual risk for having a child with spina bifida, or other serious NTDs. They will compare DNA from patients with NTDs with DNA from healthy patients with the ultimate goal of developing more individually targeted and more effective prevention strategies.

The U.S. Public Health Service recommends that all women capable of becoming pregnant should consume folic acid to reduce their risk for having a pregnancy affected by spina bifida and other NTDs. Folic acid is in most multivitamins and many foods, including vegetables like broccoli and spinach, and fruits and juices such as orange juice. Some foods also have folic acid added to them, like certain breakfast cereals and other bread and grain products. Research at Weill Cornell will address questions of how folic acid protects against neural tube defects, how the need for folic acid varies with the genetic makeup of an individual, and whether there are alternative supplements, perhaps working elsewhere in the same pathway as folic acid, that would more effectively promote healthy birth outcomes by providing a patient-specific genetic test before pregnancy begins.

In addition to the Weill Cornell award, three research scientists at Cornell University in Ithaca received a five-year Transformative Research Projects Award (T-R01) of approximately $3.04 million to fight cancer by targeting the regulation of metabolic enzymes. Drs. Richard A. Cerione, professor of pharmacology in the Department of Molecular Medicine, College of Veterinary Medicine, and professor of chemistry and chemical biology in the College of Arts and Sciences; Hening Lin, assistant professor of chemistry and chemical biology; and Robert S. Weiss, associate professor of molecular genetics in the College of Veterinary Medicine, are working on the project, "Succinylation and Malonylation as Novel Protein Modifications in Cancer." The research will focus on a new set of regulatory modifications that occur on proteins and which appear to be important to cancer progression, explain the researchers.

"More specifically, we believe that these modifications help to activate proteins that are responsible for meeting the hefty energy requirements of cancer cells. Thus, if we can block these modifications and the activation of the metabolic proteins, the cancer cells will not be able to meet their energy needs and hopefully die," says Dr. Cerione.

The Motherisk Program, located at the Hospital for Sick Children, invites women between the ages of 18 and 45 years to participate in a study about folic acid during pregnancy.

We are looking for healthy women who are planning a pregnancy or who are less than 6 weeks pregnant, but are not currently taking folic acid or multivitamins. In addition, women must not have had a previous pregnancy affected by a neural tube defect or a family history of neural tube defects.

Motherisk will provide multivitamins containing folic acid to all participants upon study inclusion and for the duration of pregnancy. These multivitamins are to be taken daily. They are approved by Health Canada and can be safely obtained from healthcare professionals and healthcare services.

Researchers at the Hospital for Sick Children will draw blood samples at 4 times during the study to measure folate levels. Folate measurements will take place at the Hospital for Sick Children (Toronto, Ontario), therefore, study participation may be most convenient for women residing in the GTA.

Participants will be paid $250 (maximum) upon completion of the study. Payments will be adjusted depending on the degree of participation.

If you would like to participate or if you would like more information, please contact the study co-ordinator, Carolyn Tam, at (416) 813-7283 or by e-mail at carolyn.tam@utoronto.ca.

The National Post reports researchers at McGill University support fortifying bread and other food with folic acid. Women should also take supplements before and around the time they get pregnant, a recommendation made by many experts.

“Folic acid is important and it reduces birth defects,” says Dr. Rima Rozen, head of the new study.

A synthetic form of naturally occurring folate, folic acid has been mandated in Canada as an addition to white flour, enriched pasta and cornmeal since 1998, with seemingly dramatic results. A 2007 study concluded rates of fetal neural tube defects had fallen by 50% per year.

The recommendation is that women consume 0.4 mg of folic acid supplements each day in the three-month period before they conceive and during the first trimester of pregnancy to achieve optimum blood levels. The latest McGill study suggests, however, that massive amounts – in this case, 20 times the recommended dosage – can be problematic, so moderation is key.

“We know there are definite benefits of folate,” says Dr. Deborah L. O’Connor, Director of Clinical Dietetics at Sick Children’s Hospital in Toronto. “[With] any nutrient, you don’t want too little, you want enough, which is about in the middle, and too much usually gets us into trouble.” What’s important, she adds, is that “possible, unproven risks associated with excessive amounts of the stuff should not dissuade anyone from taking the recommended dose.”

To read the full article, visit The National Post.

A recent report in the Journal of Biological Chemistry notes if all women who could become pregnant consumed recommend amounts of folic acid before and during pregnancy, the risks of neural tube defects such as spina bifida could be decreased by 70%. Folic acid may also prevent other birth defects, including cleft lip and palate and heart defects, which are diagnosed in the second trimester when it is too late for medical intervention. Read more...