Researchers find genetic biomarker that could indicate mental illness in women

Patients' behaviors and feelings often serve as identifying factors for psychiatric disorders, which can make diagnoses difficult. Researchers at the University of California San Diego School of Medicine have discovered that the over-production of specific genes may indicate mental illness in female psychiatric patients, according to a study published in the journal EBioMedicine.

The gene XIST, which deactivates one of the two X chromosomes in cells responsible for storing genetic material, works too hard in female patients who have mental illnesses such as bipolar disorder, major depression and schizophrenia. According to the study, over-production of XIST and genes from the inactive X chromosome are common factors in patients with psychiatric disorders and rare chromosome disorders like Klinefelter syndrome and Triple X syndrome.

"There has been an utmost urgency to identify biomarkers for mental illness that could significantly impact research and drug development, said XianJin Zhou, assistant professor in the UCSD Department of Psychiatry and lead author of the study.

About half of the participants—most of whom had a family history of mental illness—had unusually higher levels of XIST and other genes related to the X chromosome. Zhou and his team said stopping the abnormal activity of the inactive X chromosome may be a new strategy for treating those with psychiatric disorders. "These results are powerful in that early diagnosis of mental illness could possibly happen with a simple blood test, leading to better interventions, therapy and treatment options," Zhou said.

Experimental drug being used to treat Ebola is being manufactured using special tobacco plants in Owensboro

A unique type of tobacco grown in Owensboro is used to manufacture the ZMapp compound that was given to two Americans who then survived Ebola. The company that produced it, Kentucky BioProcessing, has since gone into "full-scale production of the drug," Janet Patton reports for the Lexington Herald-Leader.

"All of our focus is solely on ZMapp production. We're hoping our efforts can help expedite the drug approval process," David Howard, spokesman for Reynolds American, the tobacco company that owns the facility that makes pharmaceuticals from tobacco, told Patton. The genetic makeup of tobacco makes it an easy vehicle for genetic engineering.

The drug has been sent to government agencies for testing, but it hasn't been used on any more patients since the two Americans, Dr. Kent Brantly and Nancy Writebol, who have since recovered, were given the drug, Patton writes. She also noted that "it's uncertain whether the ZMapp helped cure Brantly or Writebol," but the drug has shown "promising results in testing in primates and mice, curing most of them even after they showed signs of infection."

ZMapp is "a cocktail of antibodies that has been proven to be the most effective treatment so far in fighting off the Ebola virus," Patton writes in a separate article. It was developed while working under contract for the U.S. Department of Defense and other federal agencies to be a "post-exposure treatment for Ebola virus."

The process involves growing a unique tobacco plant and "infecting" the plant with a protein that will "battle the Ebola." The protein then reproduces inside the tobacco plant "like a photocopier." And when ready, the desired proteins are extracted from the plants and put into a serum, Patton reports.

According to the website of Mapp Biopharmaceutical, a company that collaborates with Kentucky BioProcessing, the supply of ZMapp was used up in August, Patton reports.

In September, the federal government announced that it had given Mapp an 18-month contract for as much as $42.3 million for "the development and manufacturing of the medication ZMapp toward the goal of U.S. Food and Drug Administration approval," Patton reports.

Mapp says it is is conducting studies that will help determine the safety and efficacy of the drug while improving its manufacturing process, increasing yields and scale.

"The Department of Health and Human Services is also in advanced discussions to enlist Caliber Biotherapeutics, a Texas company that can produce the drug in millions of tobacco plants," according to federal officials and pharmaceutical industry executives, Andrew Pollack reports for The New York Times.

He reports that federal officials along with two of the world's biggest charities are also looking at arranging for production of ZMapp in animal cells, a more conventional method that takes longer, but allows for for greater output.

But even if these new contracts are negotiated, Pollack reports that there will only be "hundreds or thousands of treatment courses by early next year, which would not be nearly enough if the epidemic continues to spiral out of control."

Fragile X Syndrome, a little known disorder, is the leading inherited cause of intellectual disabilities; U of L has only clinic for it in Ky.

A common but little-known genetic disorder called Fragile X Syndrome is the leading inherited cause of intellectual disability, autism and developmental delay, and the University of Louisville is home to the only Fragile X clinic in Kentucky, the university said in a press release.

Varying levels of disability are associated with the syndrome, depending on whether the FMR1 gene associated with the condition is fully mutated or merely changed but not fully mutated, according to the release.

The federal Centers for Disease Control and Prevention explains that the FMR1 gene is responsible for making a protein that is needed for normal brain development. Those with the syndrome don't make this protein, and those with altered genes don't make enough of it.

Infants born with the fully mutated gene may have intellectual disability, autism and/or delays in development, speech and language. Those with altered genes are more likely to have milder problems in childhood, such as a learning disability or issues with anxiety and social difficulty, which can occur both in childhood and adulthood, says the release. They can also develop infertility and neurological problems such as tremors, imbalance and dementia. Some carriers of the altered genes have no symptoms.

Fragile X Syndrome affects one in approximately 4,000 men and 6,000 women, according to the release. Carriers of the altered gene, who pass it along to later generations, are much more common, with approximately one in 250 women and 800 men.

The Weisskopf Child Evaluation Center at U of L is home to one of 27 clinics affiliated with the National Fragile X Foundation.

John and Shannon Casasfranco had their 2-year-old son John, who had been diagnosed with autism, genetically tested at the center on their doctor's recommendation. They learned that he had Fragile X, and that they were both carriers of the altered gene.

They encourage families to speak to their doctor about genetic testing if they are concerned about children not meeting milestones or suspect that Fragile X is an issue in their family. “If we hadn’t have gotten John tested, we wouldn’t know anything. There is no blood test for autism but there is for Fragile X. Now we know there’s a biological reason for his disability. It’s a hard thing to swallow but you’ve got to plan,” Shannon said.

“Because of our affiliation with the Fragile X Clinical & Research Consortium, we can provide care to patients and families like the Casasfrancos that is based on the most up-to-date knowledge and recommendations of clinicians across the United States who have expertise in Fragile X,” Lisa Craft, ;medical director of the WCEC Fragile X clinic, said.

According to Craft, Fragile X genetic testing should be considered for:

• A child with autism or developmental delays
• Adults with autism or developmental disabilities with no known cause
• Adults with a tremor or balance problem, even if no family members have been diagnosed with Fragile X.
• Women with fertility problems, even if no family members have been diagnosed with Fragile X.

“With knowledge comes power. Knowing that a child or adult has Fragile X provides the family with a ‘road map’ to help them understand the individual’s needs, challenges and strengths,” Craft said. “A diagnosis helps families find the most appropriate services and connect to other families and professionals who can help them on their journey across the lifespan.”

July 22 is National Fragile X Day.