An important step towards developing a rapid, inexpensive diagnostic method for autism has been take by Uppsala University, among other universities. Through advanced mass spectrometry the researchers managed to capture promising biomarkers from a tiny blood sample.
There are no acknowledged biomarkers for autism today. Researchers at Berzelii Centre and the Science for Life Laboratory in Uppsala who, in collaboration with colleagues at Linnaeus University in Sweden and the Faculty of Medicine in Tehran, Iran, who have discovered some promising biomarkers.
Many diseases are caused by protein alterations inside and outside the body’s cells. By studying protein patterns in tissue and body fluids, these alterations can be mapped to provide important information about underlying causes of disease. Sometimes protein patterns can also be used as biomarkers to enable diagnosis or as a prognosticating tool to monitor the development of a disease. In the current study disruptions of the nervous system were in focus when the scientists studied protein patterns in autism spectrum disorder (ASD).
To identify potential biomarkers (peptides or proteins), the researchers performed a detailed protein analysis of blood plasma from children with ASD compared with a control group. Using advanced mass spectrometric methods, they succeeded in identifying peptides consisting of fragments of a protein whose natural function is in the immune system, the complement factor C3 protein.
The study is based on blood samples from a relatively limited group of children, but the results indicate the potential of our methodological strategy. There is already a known connection between this protein and ASD, which further reinforces the findings, says Jonas Bergquist, professor of analytical chemistry and neurochemistry at the Department of Chemistry – BMC (Biomedical Centre) in Uppsala.
The hope is that this new set of biomarkers ultimately will lead to a reliable blood-based diagnostic tool. Uppsala University

Why do some people experience post-traumatic stress disorder (PTSD) while others who suffered the same ordeal do not? A new UCLA study may shed light on the answer.

UCLA scientists have linked two genes involved in serotonin production to a higher risk of developing PTSD. The findings suggest that susceptibility to PTSD is inherited, pointing to new ways of screening for and treating the disorder.

‘People can develop post-traumatic stress disorder after surviving a life-threatening ordeal like war, rape or a natural disaster,’ said lead author Dr. Armen Goenjian, a research professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA. ‘If confirmed, our findings could eventually lead to new ways to screen people at risk for PTSD and target specific medicines for preventing and treating the disorder.’

PTSD can arise following child abuse, terrorist attacks, sexual or physical assault, major accidents, natural disasters or exposure to war or combat. Symptoms include flashbacks, feeling emotionally numb or hyper-alert to danger, and avoiding situations that remind one of the original trauma.

Goenjian and his colleagues extracted the DNA of 200 adults from several generations of 12 extended families who suffered PTSD symptoms after surviving the devastating 1988 earthquake in Armenia.

In studying the families’ genes, the researchers found that persons who possessed specific variants of two genes were more likely to develop PTSD symptoms. Called TPH1 and TPH2, these genes control the production of serotonin, a brain chemical that regulates mood, sleep and alertness — all of which are disrupted in PTSD.

‘We suspect that the gene variants produce less serotonin, predisposing these family members to PTSD after exposure to violence or disaster,’ Goenjian said. ‘Our next step will be to try and replicate the findings in a larger, more heterogeneous population.’

PTSD affects about 7 percent of Americans and has become a pressing health issue for a large percentage of war veterans returning from Iraq and Afghanistan. The UCLA team’s discovery could be used to help screen people who may be at risk for developing PTSD.

‘A diagnostic tool based upon TPH1 and TPH2 could enable military leaders to identify soldiers who are at higher risk of developing PTSD and reassign their combat duties accordingly,’ Goenjian said. ‘Our findings may also help scientists uncover alternative treatments for the disorder, such as gene therapy or new drugs that regulate the chemicals responsible for PTSD symptoms.’

According to Goenjian, pinpointing genes connected with PTSD symptoms will help neuroscientists classify the disorder based on brain biology instead of clinical observation. Psychiatrists currently rely on a trial-and-error approach to identify the best medication for controlling an individual patient’s symptoms. UCLA

One in eight women will be diagnosed with breast cancer during her lifetime. The earlier cancer is detected, the better the chance of successful treatment and long-term survival. However, early cancer diagnosis is still challenging as testing by mammography remains cumbersome, costly, and in many cases, cancer can only be detected at an advanced stage. A team based in the Dept. of Biomedical Engineering at McGill University’s Faculty of Medicine has developed a new microfluidics-based microarray that could one day radically change how and when cancer is diagnosed.
For years, scientists have worked to develop blood tests for cancer based on the presence of the Carcinoembryonic Antigen (CEA), a protein biomarker for cancer identified over 40 years ago by McGill’s Dr. Phil Gold. This biomarker, however, is also found in healthy people and its concentration varies from person to person depending on genetic background and lifestyle. As such, it has not been possible to establish a precise cut-off between healthy individuals and those with cancer.
‘Attempts have been made to overcome this problem of person-to-person variability by seeking to establish a molecular ‘portrait’ of a person by measuring both the concentration of multiple proteins in the blood and identifying the signature molecules that, taken together, constitute a characteristic ‘fingerprint’ of cancer,’ explains Dr. David Juncker, the team’s principal investigator. ‘However, no reliable set of biomarkers has been found, and no such test is available today. Our goal is to find a way around this.’
Dr. Mateu Pla-Roca, the study’s first author, along with members of Juncker’s team, began by analysing the most commonly used existing technologies that measure multiple proteins in the blood and developing a model describing their vulnerabilities and limitations. Specifically, they discovered why the number of protein targets that can be measured simultaneously has been limited and why the accuracy and reproducibility of these tests have been so challenging to improve. Armed with a better understanding of these limitations, the team then developed a novel microfluidics-based microarray technology that circumvents these restrictions. Using this new approach, it then became possible to measure as many protein biomarkers as desired while minimising the possibility of obtaining false results.
Juncker’s biomedical engineering group, together with oncology and bioinformatics teams from McGill’s Goodman Cancer Research Centre, then measured the profile of 32 proteins in the blood of 11 healthy controls and 17 individuals who had a particular subtype of breast cancer (oestrogen receptor-positive). The researchers found that a subset of six of these 32 proteins could be used to establish a fingerprint for this cancer and classify each of the patients and healthy controls as having or not having breast cancer.
‘While this study needs to be repeated with additional markers and a greater diversity of patients and cancer subsets before such a test can be applied to clinical diagnosis, these results nonetheless underscore the exciting potential of this new technology,’ said Juncker.
Looking ahead, Juncker and his collaborators have set as their goal the development of a simple test that can be carried out in a physician’s office using a droplet of blood, thereby reducing dependence on mammography and minimizing attendant exposure to X-rays, discomfort and cost. His lab is currently developing a hand-held version of the test and is working on improving its sensitivity so as to be able to accurately detect breast cancer and ultimately, many other diseases, at the earliest possible stage. McGill University

Virginia Commonwealth University School of Medicine researchers have discovered that changes in the gene expression of a key enzyme may contribute to high blood pressure and increase susceptibility to forming blood clots in pregnant women with preeclampsia.
These findings could provide clues to the best treatment approaches for high blood pressure and the formation of blood clots that can block blood flow to a pregnant woman’s internal organs and lead to organ failure.
Researchers have been working to determine the root cause of preeclampsia on the molecular level and have now identified that epigenetic mechanisms may be at play. Epigenetics refers to changes in gene expression that are mediated through mechanisms other than changes in the DNA sequence.
In a study published, the VCU team reported that thromboxane synthase – an important inflammatory enzyme – is increased in the blood vessels of expectant mothers with preeclampsia. The thromboxane synthase gene codes for this enzyme, which is involved in several processes including cardiovascular disease and stroke. This enzyme results in the synthesis of thromboxane, which increases blood pressure and causes blood clots.
‘The present work is unique because it opens up a new concept as to the cause and subsequent consequences of preeclampsia relating to epigenetics,’ said corresponding author Scott W. Walsh, Ph.D., professor in the VCU Department of Obstetrics and Gynecology. ‘It is the first study to show that epigenetic alterations in the blood vessels of the mother are related to preeclampsia.’
According to Walsh, one of the main epigenetic mechanisms is methylation of the DNA, which controls the expression of genes. The increase of this enzyme in the blood vessels is related to reduced DNA methylation and the infiltration of neutrophils into the blood vessels. Neutrophils are white blood cells that normally help fight infection.
In the future, Walsh said some potential treatments for preeclampsia may include inhibition of thromboxane synthase, blockade of thromboxane receptors or dietary supplementation with folate. He said that folate supplementation could increase methylation donors to protect against adverse changes in DNA methylation that affect expression of the thromboxane synthase enzyme. Virginia Commonwealth University

Scientists have identified which strains of the Toxoplasma gondii parasite, the cause of toxoplasmosis, are most strongly associated with premature births and severe birth defects in the United States. The researchers used a new blood test developed by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, to pinpoint T. gondii strains that children acquire from their acutely infected mothers while in the womb.
Pregnant women can become infected with T. gondii through contact with cat faeces that contain infectious forms of the parasite or by eating undercooked meat. Women who become infected while pregnant may miscarry, give birth prematurely, or have babies with eye or brain damage.
‘If undetected or untreated, congenital toxoplasmosis can have serious consequences for a child’s quality of life,’ noted NIAID Director Anthony S. Fauci, M.D. ‘The findings from this study support the value of screening for toxoplasmosis to identify patients who could benefit from treatment.’
Currently available blood tests can determine whether a person has ever been infected with any strain of Toxoplasma parasite. The experimental test developed at NIAID improves upon the older tests because it can detect the presence of strain-specific antibodies that distinguish infecting strains from one another. The test was developed by Michael Grigg, Ph.D., of NIAID’s Laboratory of Parasitic Diseases, and his colleagues. It was applied to blood samples collected between 1981 and 2009 as part of the National Collaborative Chicago-Based Congenital Toxoplasmosis Study. The study of congenitally infected children was initiated by NIAID grantee Rima McLeod, M.D., of the University of Chicago, who is the first author of the new study.
At least 15 distinct T. gondii strain types have been found throughout the world. In France, where research has been done to establish which strains are most common, a strain called type II predominates. Type II parasites can be distinguished from all other strains, which are collectively termed not exclusively type II strains (or NE-II).
Using the new test, the researchers found evidence of either type II or NE-II infections in 183 of the mother-child pairs in the national congenital toxoplasmosis study. Statistical analysis revealed that NE-II parasites were more likely to be associated with premature birth, and infants infected with these strains were more likely to have severe manifestations of disease than infants infected by type II parasites. For example, severe eye damage was seen in 67 percent of NE-II cases (59 out of 88), while such eye damage was present in only 39 percent of type II cases (18 out of 46). The researchers noted, however, that the association is not absolute, and that mild, moderate or severe disease can result regardless of the infecting strain.
‘We knew that, in mice, certain parasite strains are clearly associated with severe disease,’ said Dr. Grigg. ‘But we didn’t know if the same association between strain type and disease severity would hold true for people. Until now, we had not systematically determined whether infected people in the United States had European-type strains or other types, and we also hadn’t determined whether strains found here would have more severe disease symptoms associated with them.’
When she helped start the congenital toxoplasmosis study in 1981, optimal drug treatment regimens were unknown, said Dr. McLeod. Now, thanks in part to controlled clinical trials run under the auspices of the study, the condition can be successfully treated and many babies who are diagnosed before or shortly after birth and who are treated suffer few or no ill effects. When the researchers looked at the clinical histories of those children in the long-term study who had been diagnosed with congenital toxoplasmosis during gestation and whose mothers had received drug treatment prior to giving birth, the association between NE-II and severe disease at birth vanished. ‘Our study demonstrates that outcomes are equally good following postnatal treatment for type II and NE-II parasites, although not all outcomes are favorable for all children,’ she said.
In France, all pregnant women are screened for Toxoplasma infection. Prompt treatment is offered to any woman who becomes infected while pregnant, thus lessening the chance that the parasite will damage the fetus, Dr. McLeod noted. ‘In the United States, obstetrical screening for Toxoplasma infection is rarely practiced. This new study underscores the value of identifying all patients who will benefit from treatment and suggests that widespread screening and treatment of pregnant women who are infected could prevent infants from suffering eye and brain damage due to congenital toxoplasmosis,’ she said. EurekAlert