Dr Mohammed Junaid Helps Unravel Clue to Autism Cause
By Sherry Halbrook

PEF scientists may have found a small clue to solving a big mystery: What causes autism and why is it becoming so common?

The culprit might be just too much of a good thing.

The researchers at the state’s Institute for Basic Research in Developmental Disabilities (IBR) on Staten Island found folic acid, a form of vitamin B given throughout pregnancy to prevent spina bifida, might also be increasing the risk for autism, attention deficit hyperactivity disorder (ADHD) and other kinds of neuro developmental problems.

The scientists reported their findings this fall in the science journal, Biochemical and Biophysical Research Communications, that excessive amounts of folic acid cause widespread changes in the expression of genes, which can affect genes’ function and have deleterious effects.

IBR Director W. Ted Brown, MD, PhD, said, “Our finding that excessive folic acid may cause abnormal gene expression has important public health implications. Because pregnant women are prescribed additional folic acid to prevent neural-tube-closure defects (defects in early brain and nervous system development), there is a greater likelihood the developing fetus will encounter folic acid concentrations high enough to alter gene expression.”

The additional folic acid is needed in the first three months of pregnancy to prevent defects in neural tube closure that occur in the first trimester.

However, high doses of folic acid continue to be given throughout pregnancy, and the scientists are concerned that could be a problem.

Even if pregnant women stopped taking folic acid supplements after their first trimester, they might still get too much because federal guidelines require folic acid be added to cereals and grains.

PEF member Mohammed A. Junaid, PhD, head of IBR’s Structural Neurobiology Laboratory, led the research study. It showed folic acid supplementation of lymphoblastoid cells could increase or decrease by as much as four times the expression of more than 1,000 genes.

Dr. Junaid and the IBR research team, that also included PEF members Salomon Kuizon, and molecular biologist Noriko Murakami, PhD, among others, believe such abnormal expression of genes during early brain development may have lifelong adverse effects or lead to neuro developmental defects such as autism.

“We’ve been searching for years to find the genes responsible for autism,” Dr. Junaid said. “But after all of these years, that didn’t lead to an answer. So, we thought we should look for an environmental factor that could modulate genes. Not many people have looked at folic acid in this way.

“We started our research last March and, to our surprise, we found folic acid could dysregulate the expression of 1,400 genes. The most promising link to autism was FMRP.”

One of the prominent genes whose expression was found to be decreased by folic acid is FMR1, which produces the protein FMRP.

Babies that don’t get enough FMRP in the womb can develop Fragile X syndrome and that’s the most common known cause of inherited intellectual or developmental disability as well as the most common known single-gene cause of autism.

The IBR team’s study, “Folic Acid Supplementation Dysregulates Gene Expression In Lymphoblastoid Cells: Implications In Nutrition,” appears in the September issue of Biochemical and Biophysical Research Communications [2011; 412:(4):688–692] available online.

Dr. Brown, an internationally recognized expert on Fragile X syndrome, is senior author of the article. Co-authors are: Dr. Junaid, Kuizon, students Juan Cardona and Tayaba Azher, Raju K. Pullarkat, PhD, now retired from IBR’s Department of Developmental Biochemistry; and Dr. Murakami.

Dr. Junaid said he doesn’t think getting too much folic acid is likely to be autism’s sole cause.

“I don’t think just one factor causes autism. I think you would need predisposed genes, polymorphisms and environmental factors such as folic acid,” Dr. Junaid said.

“Our findings have potential, but this needs more study,” said Dr. Murakami, who has worked at IBR since 1988.

“I’m looking for a collaboration with a university to continue my research,” Dr. Junaid said. “The net effect of folic acid is going to be a very large area of study.”

“This research is one of the most exciting things I’ve done in my 33 years at IBR,” said Kuizon, who conducted many of the experiments on folic acid directed by Dr. Junaid.

Kuizon said their discovery is a great example of why government research institutions such as IBR and public funding of basic research is vital.

Corporations and the private sector do research based on the likelihood of future products and profits that might result.

“They don’t fund basic research because it doesn’t pay off fast enough,” Kuizon said.

“At IBR, we’re completely independent of any commercial influences (such as from the makers of folic acid supplements),” Kuizon said. “What we find is what we find. And people’s lives can depend on this, literally.”

 

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