Springer Nature

A precision medicine approach has advanced the development of new cancer therapies and researchers who study neurodegenerative diseases would like to replicate that model. Yet, few neurologists recommend genetic testing to patients with neurodegenerative disorders such as Parkinson’s disease. Dr. Roy Alcalay, a neurologist and associate professor at Columbia University Irving Medical Center, and colleagues wanted to discover what’s holding them back. In a recent study published in GIM, the team conducted a survey to identify what barriers exist for movement disorder specialists in the US and Canada. Tune in to this month’s GenePod to find out how knowledge gaps, insurance coverage questions and attitudes toward therapeutic approaches contribute to clinicians’ hesitancy to recommend genetic testing for neurodegenerative disease patients.

Related article:

'Genetic testing for Parkinson disease: current practice, knowledge, and attitudes among US and Canadian movement disorders specialists'

https://www.nature.com/articles/s41436-019-0684-x

It’s widely understood that early life adversity has an impact on mental illness and cognitive problems later in life. There are theories as to the mechanisms of how this works, but it’s difficult to test in humans. Tallie Baram is a professor of neurophysiology and biophysics at the UC Irvine department of pediatrics. And she co-authored a recent study in the journal Neuropsychopharmacology with Ali Mortazavi, professor of developmental and cell biology at UC Irvine. Dr. Baram says that imaging studies show changes in brain structure and circuits, and cognitive and emotional tests also demonstrate a change in function. But it’s difficult to study the mechanism, to try to understand how this is happening, because scientists can’t take samples of brain tissue to determine how and when genes are expressed.

Related Link: https://www.nature.com/articles/s41386-019-0496-3

Although genetic sequencing has aided the diagnosis of many genetic diseases, only about one third of children with unknown or rare genetic diseases end up with a diagnosis after exome sequencing. To help these patients, Stanley Nelson, professor of human genetics at the David Geffen School of Medicine at UCLA, wanted to explore the genome more effectively. In a recent publication in GIM, Dr. Nelson and team show RNA sequencing helped to solve an additional 15% of cases that genome sequencing alone couldn't. On this month's podcast, Dr. Nelson and host Cynthia Graber discuss how transcriptome sequencing may be able to shorten the diagnostic odyssey for some rare disease patients and whether insurance companies should pay for the testing.

Related link - https://www.nature.com/articles/s41436-019-0672-1

One of the most common chromosomal deletions in humans happens on chromosome 22. It’s known as 22q and affects as many as one in 2,000 live births. People with the deletion can present with a wide variety of traits. Some have heart defects. Others have defects in the palate, while still others have developmental delays. But in 2005, Donna McDonald-McGinn, director of the 22Q and You Center at the Children’s Hospital of Philadelphia and clinical professor at the University of Pennsylvania, noticed some patients had rare, atypical clinical features such as limb differences and rectal malformations. Now, in a recent publication in GIM, she and an international team of scientists reveal variants in a gene called CDC45 on the non-deleted chromosome are responsible for the unusual traits. The 22q deletion had unmasked the effects of the CDC45 variants. On this month’s GenePod podcast, Dr. McDonald-McGinn and host Cynthia Graber chat about how this unmasking phenomenon may be responsible for other conditions as well.

Related article -

https://www.nature.com/articles/s41436-019-0645-4

Neonatal encephalopathy (NE) is associated with substantial morbidity and mortality and affects around 1.5/1000 live term births. Predicting the severity and outcome of neonates with NE is therefore vital in order to provide the best care for neonates with NE, and a biochemical marker obtained at birth would therefore be useful to bolster the current scoring system. In this episode, Geoff Marsh speaks to Early Career Investigator Dr. Imran Nazir Mir, from the University of Texas, Southwestern Medical Center. He's just published a paper testing the utility of two potential candidate proteins for determining the presence and severity of hypoxic NE, and to understand where these molecules are synthesized and cleared.

Related article:

https://www.nature.com/articles/s41390-019-0439-z

The recreational drug MDMA, also known as Ecstasy or Molly, is particularly popular in social settings and raves, in large part because of how socially connected it makes the users feel. It’s being studied for use in psychotherapy —there’s a phase III clinical trial for the use of MDMA to treat PTSD. What’s clear is that the drug affects how users experience social interactions. But there are questions: Does the drug make positive social interactions feel better, or reduce the negative feelings associated with negative social interactions?

Related link -

https://www.nature.com/articles/s41386-019-0402-z

Every year more than half a million people in the US have stents placed in narrow blood vessels to improve blood flow to the heart. Following the procedure, patients typically need treatment with anti-clotting drugs. The go-to medication is clopidogrel, a prodrug that requires activation by an enzyme called CYP2C19. However, about a third of patients carry variants that render CYP2C19 ineffective. These patients are at increased risk for future heart attacks, strokes and other cardiovascular events. Prasugrel and ticagrelor are examples of alternative anti-clotting medications, but these therapies have been shown to have higher bleeding rates and are typically more expensive than clopidogrel. In clinical practice, switching between clopidogrel and either prasugrel or ticagrelor has become common. In a recent study published in GIM, researchers demonstrate how using CYP2C19 genotyping to guide medication decisions can benefit patients. GenePod host Cynthia Graber chats with the study’s lead author, Dr. Craig Lee, about the work on this month’s podcast.

Article Link:

https://www.nature.com/articles/s41436-019-0611-1

For term-born infants, low birth weight has been shown to correlate with a broad array of adverse cardiometabolic outcomes, and excess glucocorticoid exposure has been linked to these relationships. Also, intra-uterine growth restriction (IUGR) in term-born infants has been linked to subsequent increases in adrenal androgen activity. In this episode, we meet Kristi Watterberg, a professor of Pediatrics at the University of New Mexico who evaluated the relationship between preterm birth to salivary cortisol and dehydroepiandrosterone (DHEA) at age 6, and assessed the relationship of cortisol and DHEA with blood pressure and measures of adiposity. The results suggest interventions to improve the cardiometabolic outcomes of infants born extremely preterm.

Article link:

https://www.nature.com/articles/s41390-018-0243-1

Over-the-counter (OTC) medications are used in an estimated 70% of pregnancies. Acetaminophen, also known as paracetamol is found in a large number of OTC and prescription drugs.

Given its prevalence and its ability to freely cross the placenta, researchers are now focusing on the safety of maternal exposure to this drug and its effects on fetal health. There have been inconsistent results in both human and animal studies on the short and long-term effects of acetaminophen use during pregnancy.

In this episode, we meet Early Career Investigator, Melissa Smarr, an assistant professor at the Emory University School of Public Health as she describes her study into the effects of prenatal acetaminophen use on fetal growth.

As the appetite for clinical genetic testing grows, it seems the demand for geneticists able to provide the needed services outpaces the supply. Yet health services do not have a way to measure that growth or the resources needed to provide those services. In a recent study published in GIM, researchers describe a new framework for evaluating the resource needs of clinical genetics services, including recent huge increases in genetic testing and the accompanying counseling. In the August Genepod, host Cynthia Graber talks with lead study author Andrew Fennell about the new framework, its current limitations and how clinicians can use it now to plan for the future.

Related link;

https://www.nature.com/articles/s41436-019-0602-2