Variants Indicate a Type II Diabetes Predisposition

An international team co-led by scientists from the University of Michigan has discovered 12 more regions on the genome with DNA variants that are associated with increased risk of Type II diabetes, bringing the number to 38.

Researchers also wanted to know if people who hadn't yet developed Type II diabetes, but did have the diabetes variant showed elevated blood glucose levels, a main predictor of diabetes. The study suggested that many of these variants are associated with changes in glucose levels long before people get diabetes.

One surprising finding was that the regions with diabetes variants also seemed to be associated with nonrelated diseases. Researchers looked at a database containing a list of all the genomewide association (GWA) studies to date. They examined regions where there was a Type II diabetes association to see if there was an increased association for other diseases and traits that have been studied thus far. Researchers reported finding an overlap, or predisposition, of not just related, but also apparently unrelated traits.

The next step is to take the research beyond GWA, which looks at a few million places on the genome, into genome sequencing. Genome sequencing will allow researchers to assay most of the 3 billion base pairs in the human genome and find less common variants that might be associated with disease. Currently, a three-study international team co-led by the Michigan group is sequencing 2,650 individuals with and without diabetes, in what is one of the largest sequencing projects underway in the world.

These findings appeared online June 27 in Nature Genetics.

Hallmark AD Changes Found in Retinas

The nerve cell-damaging plaque that builds up in the brain with Alzheimer's disease also builds up in the retinas of the eyes – and it shows up there earlier, leading to the prospect that noninvasive optical imaging of the eyes could lead to earlier diagnosis, intervention and monitoring of the disease, according to new research.

Scientists discovered characteristic amyloid plaques in retinas from deceased Alzheimer's disease patients and used a noninvasive optical imaging technique to detect retinal plaques in live laboratory mice genetically modified to model the human disease. The combined results suggested the possibility that noninvasive retinal imaging may be helpful in early diagnosis of the disease.

The research was conducted by a team of scientists at Cedars-Sinai Medical Center in collaboration with colleagues from the Weizmann Institute of Science in Israel and the University of Southern California. Results were published in NeuroImage.

Previous studies have suggested that changes in the brain may begin years or even decades before symptoms occur – emphasizing the need for earlier, reliable detection for early therapeutic intervention to achieve effective remedy. The new study suggested the possibility of monitoring Alzheimer's disease through a simple retinal imaging approach.

Beta-amyloid plaques, which damage cells and interrupt cell-to-cell communications, are recognized as a hallmark sign of the disease. However, because existing noninvasive brain-imaging technologies cannot provide sufficient detail about these changes, the most definitive diagnosis of Alzheimer's disease comes after an autopsy.

The research team considered the retina a better target for noninvasive imaging of Alzheimer's disease because it is readily accessible and, unlike other components of the eye, it is part of the central nervous system, having a direct connection and thus many similarities with the brain. Previous studies have documented nonspecific visual disturbances, eye disorders and certain types of retinal abnormalities occurring with Alzheimer's disease and other neurodegenerative conditions, but this is the first to identify human retinal plaque deposits that could provide a specific diagnostic marker of Alzheimer's disease.

The research team used a fluorescent compound called curcumin to label and detect retinal plaques. This is believed to be the first use of curcumin as an imaging agent to detect Alzheimer's disease-related plaques in the retinas of live animals. Observations from multiple genetically engineered mouse models of Alzheimer's disease demonstrated a correlation between retinal plaques and brain plaques as disease progressed.

Beta-amyloid plaques were also identified in retinal samples from human patients who had died from Alzheimer's disease, and their features correlated with the diagnosed stage of the disease. Importantly, plaques were clearly detected not only in patients who definitely had the disease, but also in the retinas of some people who were suspected of having early-stage Alzheimer's disease based on clinical diagnosis and microscopic examination of brain tissue after death.

Together, the results offer the first evidence for the existence of Alzheimer's-specific plaques in the retina of human patients and the ability to detect individual plaques in live mouse models, creating a strong basis for future research building on these findings.

Basis of Alopecia Areata Found

Using cases from the National Alopecia Areata Registry, a team of investigators from Columbia University Medical Center has found eight genes that contribute to alopecia areata, one of which has a possible role in the onset of the disease.

The findings were published July 1, 2010 in Nature Journal.

Alopecia areata is an autoimmune skin disease that may result in total or partial loss of hair, a condition for which there is no cure. Part of the significance of this recent finding is that many of the genes found to be associated with alopecia areata are also associated with other autoimmune diseases, including rheumatoid arthritis, Type I diabetes and celiac disease; all autoimmune diseases with pre-existing treatments. This discovery, therefore, is expected to lead to effective clinical trials.

Alopecia areata is a cyclical disease having bald patches appear and, in most cases grow back, only to appear again. In many instances, the bald patches can progress to a more extreme, yet rare, form of the disease, alopecia totalis which is total scalp hair loss or alopecia universalis, resulting in the total loss of all body hair. Included in the discovery is the ability to now predict with accuracy the progression of the disease in a patient. Using the number of genes associated with disease as the marker, a genetic test has been created that can indicate the severity of disease. For the patient, this means that one will be able to determine the likelihood of a bald patch progressing to complete body hair loss.

Stem Cell Therapy May Fight Infection

A new study from researchers in Ottawa and Toronto suggested that a commonly used type of bone marrow stem cell may be able to help treat sepsis, a deadly condition that can occur when an infection spreads throughout the body.

The study, published in the American Journal of Respiratory and Critical Care Medicine, showed that these cells can triple survival rates in an experimental model of sepsis.

This work was a collaboration between research groups at the Ottawa Hospital Research Institute, St. Michael's Hospital and the University Health Network in Toronto.

Mesenchymal stem cells were tested in mice with sepsis. Bacteria from the gut were released into the abdomen, resulting in severe infection, inflammation and organ damage throughout the body. Six hours after inducing the infection, approximately half the mice were given an intravenous injection of mouse mesenchymal stem cells, while the other half received a control injection of a salt solution. Both groups of animals also received antibiotics, which is the standard treatment for sepsis in the clinic. After five days, 50 percent of the animals that received the cells were alive, compared to just 15 percent of the control animals that did not receive the cells.

Other experiments showed that mice that were treated with mesenchymal stem cells had healthier lungs and other organs, lower levels of bacteria and a more moderate level of inflammation. Further analysis revealed that the treatment caused a global change in the expression of genes that are associated with inflammation, such that the damaging effects of inflammation were reduced while the ability to clear the infection was increased.

The results suggested that mesenchymal stem cells may provide a promising new approach for treating organ damage caused by severe infection and researchers are looking to test this in patients in the near future.

Silencing HBV and Liver Cancer

Previous studies have shown that antiviral treatment reduces the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). But now, researchers from the division of gastroenterology and hepatology at Thomas Jefferson University are reporting that the antiviral therapy also prevents recurrence of HCC and extends patients' lives.

The standard of care for patients with HCC is local ablation of the tumor, unless it is large or has metastasized. However, HCC tumors often recur, or new lesions develop. In the International Journal of Cancer scientists reported that the median survival in patients who received antiviral therapy after HCC diagnosis was 60 months. In those who did not receive antiviral therapy, the median survival was 12.5 months.

Before the antiviral drugs were developed, patients would often develop new lesions within a few months of tumor ablation because the underlying virus causing the liver cancer wasn't treated. By suppressing the virus and making it undetectable, survival is extended, according to the report.

The small study included 15 CHB patients who received local ablation of a single HCC tumor that was less than four cm. The first six patients were diagnosed between 1991 and 1997, prior to the development of antiviral therapy. These patients were considered historical controls.

The other nine patients were diagnosed between 2000 and 2004. These patients began ongoing antiviral therapy with lamivudine immediately after HCC diagnosis. Other antiviral medications, such as tenofovir and adefovir were added to the regimen if resistance to lamivudine developed, or even without drug resistance.

All patients who received the antiviral therapy maintained undetectable hepatitis B virus in serum and continued the therapy. Seven of the nine patients have not developed a new HCC or recurrence. The longest survivors are the two patients who came with HCC in 2000. They are doing well, free of cancer for more than 10 years.