Unlocking a mystery of thalidomide

May 1, 2014, Tel Aviv University
Unlocking a mystery of thalidomide

In the 1950s and 1960s, pregnant women with morning sickness were often prescribed the new drug thalidomide. Shortly after the medicine was released on the market, a reported 10,000 infants were born with an extreme form of the rare congenital phocomelia syndrome, which caused death in 50 percent of cases and severe physical and mental disabilities in others. Although various factors are now known to cause phocomelia, the prominent roots of the disease can be found in the use of the drug thalidomide.

Now, half a century later, new research by Dr. Noam Shomron, Prof Arkady Torchinsky, and doctoral student Eyal Mor at Tel Aviv University's Sackler Faculty of Medicine, published in Archives of Toxicology, identifies a regulator responsible for the malformation of limbs in phocomelia, pinpointing a specific target for possible future intervention.

"We were reading old textbooks from the 1950s and '60s, trying to understand the studies carried out then on this intriguing topic, and we saw that we could undertake an in-depth examination of the disorder's processes using careful planning and execution of experiments on mouse and rat models," said Dr. Shomron. "We hoped to gain a much better understanding of embryo malformation."

In the genes

Prof. Torchinsky worked together with Mor to carry out an experiment on animal models in the laboratory. They injected mice and rats with an embryo malformation factor or "teratogen" (called 5-aza-2'-deoxycytidin) with effects similar to . The chemical is also used in chemotherapeutics. With the factor, the researchers induced phocomelia in either the forelimbs or hind limbs of the animals.

Afterward, by analyzing the entire gene and tiny regulatory RNA molecules called microRNAs in all the mouse limbs (both healthy and afflicted), the researchers were able to pinpoint the genetic regulator—the precise "switch" turned on or off during genetic processes—responsible for the malformation, p53, and its downstream target gene, MicroRNA34.

"We have added another perspective to the overall picture by investigating the genetic mechanisms involved—in other words, the gene expression rather than the genetic code affected during pathology," said Dr. Shomron. "I expect that further understanding of the mechanisms involved in teratogens and how they induce phocomelia will help reveal the dangers associated with toxins and will also reveal the underlying functional role of genes and microRNAs modulating genetic expression in the process."

Dr. Shomron said the work carried out by the team addresses a long-standing paradigm of limb malformation in mammals and reflects the role that epigenetic regulation, as opposed to genetic regulation, plays in the development of disease. In other words, embryonic development can be caused by a genetic mutation (a "mis-print" in the book of life) or, in this case, by turning the genes on or off without any change in the genetic code itself. Dr. Shomron and his team are currently studying the effects of other toxins on the mal-development of mammalian embryos.

Explore further: Severe forms of congenital heart disease caused by variants of the NR2F2 gene

Related Stories

Severe forms of congenital heart disease caused by variants of the NR2F2 gene

April 8, 2014
(Medical Xpress)—Researchers have explored the role of a master gene that controls the functioning of other genes involved in heart development. Variations in this gene - NR2F2 - are responsible for the development of severe ...

Sniffing out schizophrenia: Neurons in the nose could be the key to early, fast, and accurate diagnosis

April 29, 2013
(Medical Xpress)—A debilitating mental illness, schizophrenia can be difficult to diagnose. Because physiological evidence confirming the disease can only be gathered from the brain during an autopsy, mental health professionals ...

Important discovery for the diagnosis of genetic diseases

January 16, 2014
A study conducted by Marie Kmita's team at the IRCM, in collaboration with Josée Dostie at McGill University, shows the importance of the chromatin architecture in controlling the activity of genes, especially those required ...

Recommended for you

Rise in preterm births linked to clinical intervention

January 18, 2018
Research at the University of Adelaide shows preterm births in South Australia have increased by 40 percent over 28 years and early intervention by medical professionals has resulted in the majority of the increase.

New report calls into question effectiveness of pregnancy anti-nausea drug

January 17, 2018
Previously unpublished information from the clinical trial that the U.S. Food and Drug Administration relied on to approve the most commonly prescribed medicine for nausea in pregnancy indicates the drug is not effective, ...

New study finds 'baby brain' is real, but the cause remains mysterious

January 15, 2018
So-called "baby brain" refers to increased forgetfulness, inattention, and mental "fogginess" reported by four out of five pregnant women. These changes in brain function during pregnancy have long been recognised in midwifery ...

Sleep quality improves with help of incontinence drug

January 12, 2018
A drug used to curtail episodes of urinary incontinence in women also improves quality of sleep, a researcher at the Stanford University School of Medicine reports.

Frozen embryos result in just as many live births in IVF

January 10, 2018
Freezing and subsequent transfer of embryos gives infertile couples just as much of a chance of having a child as using fresh embryos for in vitro fertilization (IVF), research from Ho Chi Minh City, Vietnam, and Adelaide, ...

Study suggests air pollution breathed in the months before and after conception increases chance of birth defects

January 8, 2018
A team of researchers with the University of Cincinnati and Cincinnati Children's Hospital has found evidence that indicates that pre-and post-pregnant women living in an area with air pollution are at an increased risk of ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.