Category Archives: Gene Medicine

New York, April 15 (IANS): Women born with a special gene are at greater risk of developing Alzheimer's disease than men with the same disease, a study reveals.

While women with ApoE4 gene were 81 percent more likely to develop Alzheimer's disease when compared to women who did not have the gene, in men, the gene increases the risk only by 27 percent compared with men without the gene, the study said.

Figuring out the reason for this sex difference may help researchers better understand what causes Alzheimer's disease, said researcher Andre Altmann from Stanford University School of Medicine.

For the study, the researchers examined information from more than 5,000 healthy older adults in the US who did not have Alzheimer's or other types of cognitive problems, and about 2,200 people with mild cognitive impairment.

The researchers noted that about 950 healthy older adults progressed to developing Alzheimer's disease or mild cognitive impairment.

The study, that appeared in the journal Annals of Neurology, indicates that doctors may need to change the way they interpret the finding of an ApoE4 gene in people, depending the patient's sex.

See original here:
Women more vulnerable to Alzheimer's gene: Study

PUBLIC RELEASE DATE:

14-Apr-2014

Contact: Bruce Goldman goldmanb@stanford.edu 650-725-2106 Stanford University Medical Center

STANFORD, Calif. Carrying a copy of a gene variant called ApoE4 confers a substantially greater risk for Alzheimer's disease on women than it does on men, according to a new study by researchers at the Stanford University School of Medicine.

The scientists arrived at their findings by analyzing data on large numbers of older individuals who were tracked over time and noting whether they had progressed from good health to mild cognitive impairment from which most move on to develop Alzheimer's disease within a few years or to Alzheimer's disease itself.

The discovery holds implications for genetic counselors, clinicians and individual patients, as well as for clinical-trial designers. It could also help shed light on the underlying causes of Alzheimer's disease, a progressive neurological syndrome that robs its victims of their memory and ability to reason. Its incidence increases exponentially after age 65. An estimated one in every eight people past that age in the United States has Alzheimer's. Experts project that by mid-century, the number of Americans with Alzheimer's will more than double from the current estimate of 5-6 million.

According to the Alzheimer's Association, it is already the nation's most expensive disease, costing more than $200 million annually. (The epidemiology of mild cognitive impairment is fuzzier, but this gateway syndrome is clearly more widespread than Alzheimer's.)

The number of women with Alzheimer's far exceeds that of men with the condition. That's partly because women on average live longer than men. But greater longevity explains only part of women's increased susceptibility to Alzheimer's. "Even after correcting for age, women appear to be at greater risk," said Michael Greicius, MD, assistant professor of neurology and neurological sciences and medical director of the Stanford Center for Memory Disorders.

Greicius was the senior author of a study, to be published April 14 in the Annals of Neurology, in which he and his colleagues analyzed records on more than 8,000 people, most of them older than 60, who have been monitored over time at any one of about 30 Alzheimer's centers nationwide. Postdoctoral scholar Andre Altmann, PhD, was the lead author.

The records were stored in two large, publicly available repositories. In one, the researchers analyzed clinical assessments of 5,000 people whose test results were normal at the outset and 2,200 people who had initially showed signs of mild cognitive impairment. In both groups, being an ApoE4 carrier increased the likelihood of Alzheimer's disease, as expected. But a closer look revealed that among those who initially tested normal, this increased risk was only marginal for men, whereas women who carried the ApoE4 variant had close to twice the likelihood of progressing to mild cognitive impairment or Alzheimer's disease as those who didn't.

Read more here:
Gene variant puts women at higher risk of Alzheimer's than it does men, study finds

PUBLIC RELEASE DATE:

14-Apr-2014

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center

STANFORD, Calif. As many as 10 percent of women with a personal or family history of breast or ovarian cancer have at least one genetic mutation that, if known, would prompt their doctors to recommend changes in their care, according to a new study by researchers at the Stanford University School of Medicine.

The women in the study did not have mutations in BRCA1 or BRCA2 (mutations in these genes are strongly associated with hereditary breast and ovarian cancer), but they did have mutations in other cancer-associated genes.

The study was conducted using what's known as a multiple-gene panel to quickly and cheaply sequence just a few possible genetic culprits selected by researchers based on what is known about a disease. Although such panels are becoming widely clinically available, it's not been clear whether their use can help patients or affect medical recommendations.

"Although whole-genome sequencing can clearly be useful under the right conditions, it may be premature to consider doing on everyone," said James Ford, MD, who directs Stanford's Clinical Cancer Genetics Program. "Gene panels offer a middle ground between sequencing just a single gene like BRCA1 that we are certain is involved in disease risk, and sequencing every gene in the genome. It's a focused approach that should allow us to capture the most relevant information."

Ford, an associate professor of medicine and of genetics, is the senior author of the study, which will be published April 14 in the Journal of Clinical Oncology. Allison Kurian, MD, assistant professor of medicine and of health research and policy, and associate director of the Clinical Cancer Genetics Program, is the study's lead author.

Ford was a co-author on a recent paper in the in The Journal of the American Medical Association that highlighted the challenges and opportunities of making whole-genome sequencing clinically available for seemingly healthy people. Although that study showed that whole-genome sequencing can be potentially life-saving, the challenges involved in sequencing the billions of nucleotides that make up all of a person's DNA, and then translating the results into clinical care recommendations, is significant.

"This study indicates that using gene panels to screen for potentially harmful variants can be clinically useful in certain groups of patients," said Kurian. "It also shows that patients, some of whom had given blood samples for research as many as 10 years earlier, are willing and interested to receive this type of follow-up information and to incorporate it into their health care plans."

Read the original:
Gene panels may be useful, cheaper alternative to whole-genome sequencing, study finds

Published: 10:00AM Sunday April 13, 2014 Source: John Hudson

When Angelina Jolie announced last year she'd had her healthy breasts removed to lower her risk of developing breast cancer it created headlines across the globe.

Not because Ms Jolie had the BRCA1 gene, nor because she was told she had an 87 per cent chance of getting breast cancer - it was because she is a major celebrity.

There are thousands of women who have elective surgery for the same reasons without getting a mention in the press.

However what the coverage highlighted is how genetic testing is changing medicine and how the speed of that change is increasing.

If you know you've got a gene that is going to mean you will almost certainly get bowel cancer by the time you are 50 you can start to do something about it.

So when I heard about a group of specialists here in New Zealand whose job is to hunt down mutant genes I was intrigued.

These gene detectives quietly get alongside families who have often been plagued by cancer-causing genes for generations and offer them solutions which will "hugely decrease" their chance of getting cancer.

Heading the Auckland-based team is Associate Professor Susan Parry, a gastroenterologist.

"Some people just want to deny what's going on, it's not pleasant and they don't want to face up to this condition running in the family, particularly as it involves unpleasant tests." Dr Parry says.

See the rest here:
My story - "Gene Detectives"

PUBLIC RELEASE DATE:

10-Apr-2014

Contact: Lee-Ann Donegan leeann.donegan@uphs.upenn.edu 215-349-5660 University of Pennsylvania School of Medicine

(PHILADELPHIA) Researchers at Penn Medicine have discovered that the tumor suppressor gene folliculin (FLCN) is essential to normal lung function in patients with the rare disease Birt-Hogg-Dube (BHD) syndrome, a genetic disorder that affects the lungs, skin and kidneys. Folliculin's absence or mutated state has a cascading effect that leads to deteriorated lung integrity and an impairment of lung function, as reported in their findings in the current issue of Cell Reports.

"We discovered that without normal FLCN the alveolar epithelial cells (AEC) in these patients' lungs began to die, leading to holes in the lungs that grow as increasing numbers of cells disappear. These holes can fill with air and burst, causing the lungs to collapse," says Vera Krymskaya, PhD, MBA, associate professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania, and researcher in the Airway Biology Initiative of the department of Pulmonary, Allergy and Critical Care.

Between 80 and 100 percent of patients with BHD will develop multiple holes or cysts in the lung.

Healthy human alveoli, the terminal ends of the respiratory tree, are lined with type I and type II alveolar epithelial cells (AECs), a renewable population of progenitors in these distal airspaces. AECs are known to maintain pulmonary alveolar homeostasis by regulating gas exchange and fluid transport in the lungs.

Previous studies have shown that there might be some crosstalk between FLCN and the master energy sensor AMP-activated protein kinase (AMPK). AMPK maintains epithelial cell to cell interactions and is essential for epithelial cell survival. It is regulated through LKB1, a tumor suppressor gene associated with 30 percent of lung cancers. E-cadherin, the "zipper" molecule that connects epithelial cells, directs LKB1 to cell junctions and its loss impairs LKB1-mediated AMPK activation. This implies that a loss of or mutation in FLCN can trigger a reaction that can impair AMPK activation, epithelial cell to cell interaction and structure, and as a result, promotes cell death.

Penn researchers set out to examine this hypothesis to determine how and why this occurs.

Krymskaya and her team tested both deleted FLCN in mouse lung type II alveolar epithelial cells and mutated FLCN that lacked normal function in both humans with BHD and mouse epithelial cell systems, and compared them with normal human and mouse control cells.

Read more:
Penn study finds mechanism that regulates lung function in disease Birt-Hogg-Dube syndrome

PUBLIC RELEASE DATE:

10-Apr-2014

Contact: Karen Kreeger karen.kreeger@uphs.upenn.edu 215-349-5658 University of Pennsylvania School of Medicine

PHILADELPHIA The consequences of modern life -- shift work, cell phone addiction, and travel across time zones -- all disturb internal clocks. These are found in the brain where they regulate sleep and throughout the body where they regulate physiology and metabolism. Disrupting the clocks is called circadian misalignment, which has been linked to metabolic problems, even in healthy volunteers.

Researchers from the Perelman School of Medicine at the University of Pennsylvania and the University of Memphis describe in PLOS Genetics the development of new cell models that track and report clock gene function. These engineered cells can be used with inexpensive, off-the-shelf recording devices, making them suitable for small basic labs to large-scale pharmaceutical firms to screen candidate small molecules to help the body's clock function normally.

The team started with liver cells and fat cells because they govern the body's energy processing and storing system and genetically engineered them to flash light with a daily rhythm much like an alarm clock. They validated the cell models and showed that changing clock gene function in these cells is similar to what happens in mice lacking clock genes.

"The previous cellular models were great," says co-senior author John Hogenesch, Ph.D., professor of Pharmacology at Penn. "But these older cell models needed high-end imaging equipment that is out of reach for most labs and early-stage startups." By expanding the number of labs that can do these studies, these models could catalyze better understanding of peripheral clocks, as well as new genetic and chemical tools to improve their function.

"We are very excited about the prospect of using these more physiologically relevant cell-based models for gene and small molecule drug discoveries," says co-senior author Andrew Liu, from the University of Memphis.

###

For more information, visit the University of Memphis FedEx Institute of Technology site summary.

See the original post:
New cell models for tracking body clock gene function will help find novel meds

Contact Information

Available for logged-in reporters only

Newswise (PHILADELPHIA) Researchers at Penn Medicine have discovered that the tumor suppressor gene folliculin (FLCN) is essential to normal lung function in patients with the rare disease Birt-Hogg-Dube (BHD) syndrome, a genetic disorder that affects the lungs, skin and kidneys. Folliculins absence or mutated state has a cascading effect that leads to deteriorated lung integrity and an impairment of lung function, as reported in their findings in the current issue of Cell Reports.

We discovered that without normal FLCN the alveolar epithelial cells (AEC) in these patients lungs began to die, leading to holes in the lungs that grow as increasing numbers of cells disappear. These holes can fill with air and burst, causing the lungs to collapse, says Vera Krymskaya, PhD, MBA, associate professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania, and researcher in the Airway Biology Initiative of the department of Pulmonary, Allergy and Critical Care.

Between 80 and 100 percent of patients with BHD will develop multiple holes or cysts in the lung.

Healthy human alveoli, the terminal ends of the respiratory tree, are lined with type I and type II alveolar epithelial cells (AECs), a renewable population of progenitors in these distal airspaces. AECs are known to maintain pulmonary alveolar homeostasis by regulating gas exchange and fluid transport in the lungs.

Previous studies have shown that there might be some crosstalk between FLCN and the master energy sensor AMP-activated protein kinase (AMPK). AMPK maintains epithelial cell to cell interactions and is essential for epithelial cell survival. It is regulated through LKB1, a tumor suppressor gene associated with 30 percent of lung cancers. E-cadherin, the zipper molecule that connects epithelial cells, directs LKB1 to cell junctions and its loss impairs LKB1-mediated AMPK activation. This implies that a loss of or mutation in FLCN can trigger a reaction that can impair AMPK activation, epithelial cell to cell interaction and structure, and as a result, promotes cell death.

Penn researchers set out to examine this hypothesis to determine how and why this occurs.

Krymskaya and her team tested both deleted FLCN in mouse lung type II alveolar epithelial cells and mutated FLCN that lacked normal function in both humans with BHD and mouse epithelial cell systems, and compared them with normal human and mouse control cells.

The control cells showed normal epithelial structure, while the mutated FLCN cells showed irregular and disrupted lung cell structure. In addition, the BHD lungs showed very little FLCN in the type II alveolar epithelial cells.

Read more:
Penn Researchers Determine Mechanism by Which Lung Function is Regulated in Rare Disease Known As Birt-Hogg-Dube ...

Researchers at Penn Medicine have discovered that the tumor suppressor gene folliculin (FLCN) is essential to normal lung function in patients with the rare disease Birt-Hogg-Dube (BHD) syndrome, a genetic disorder that affects the lungs, skin and kidneys. Folliculin's absence or mutated state has a cascading effect that leads to deteriorated lung integrity and an impairment of lung function, as reported in their findings in the current issue of Cell Reports.

"We discovered that without normal FLCN the alveolar epithelial cells (AEC) in these patients' lungs began to die, leading to holes in the lungs that grow as increasing numbers of cells disappear. These holes can fill with air and burst, causing the lungs to collapse," says Vera Krymskaya, PhD, MBA, associate professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania, and researcher in the Airway Biology Initiative of the department of Pulmonary, Allergy and Critical Care.

Between 80 and 100 percent of patients with BHD will develop multiple holes or cysts in the lung.

Healthy human alveoli, the terminal ends of the respiratory tree, are lined with type I and type II alveolar epithelial cells (AECs), a renewable population of progenitors in these distal airspaces. AECs are known to maintain pulmonary alveolar homeostasis by regulating gas exchange and fluid transport in the lungs.

Previous studies have shown that there might be some crosstalk between FLCN and the master energy sensor AMP-activated protein kinase (AMPK). AMPK maintains epithelial cell to cell interactions and is essential for epithelial cell survival. It is regulated through LKB1, a tumor suppressor gene associated with 30 percent of lung cancers. E-cadherin, the "zipper" molecule that connects epithelial cells, directs LKB1 to cell junctions and its loss impairs LKB1-mediated AMPK activation. This implies that a loss of or mutation in FLCN can trigger a reaction that can impair AMPK activation, epithelial cell to cell interaction and structure, and as a result, promotes cell death.

Penn researchers set out to examine this hypothesis to determine how and why this occurs.

Krymskaya and her team tested both deleted FLCN in mouse lung type II alveolar epithelial cells and mutated FLCN that lacked normal function in both humans with BHD and mouse epithelial cell systems, and compared them with normal human and mouse control cells.

The control cells showed normal epithelial structure, while the mutated FLCN cells showed irregular and disrupted lung cell structure. In addition, the BHD lungs showed very little FLCN in the type II alveolar epithelial cells.

Next, to evaluate the role of FLCN in the lung, the team isolated the alveolar epithelial cells from the mice with FLCN and deleted the gene in vitro to show the decreased cell to cell interactions and increased cellular permeability. They also examined activity of AMPK in these cells and saw that cells were dying without FLCN, so there was not proper activation of AMPK.

FLCN-deficient mice were also given a doxycycline supplement to conditionally delete FLCN specifically in alveolar epithelial type II cells both during embryonic development and as adults. Newborns experienced developmental changes induced by FLCN deletion in the lung epithelium. Over time, these morphed into changes that resembled emphysema, such as alveolar enlargement and a decline in lung elasticity and pulmonary function.

Here is the original post:
Mechanism that regulates lung function in disease Birt-Hogg-Dube syndrome found

By Dennis Thompson HealthDay Reporter Latest Diet & Weight Management News

WEDNESDAY, April 9, 2014 (HealthDay News) -- An enzyme in the fat and liver of mice could take a key role in future attempts to battle obesity and type 2 diabetes, according to a new study.

The enzyme -- nicotinamide N-methyltransferase, or NNMT -- appears to help regulate the ability of cells to burn energy efficiently, researchers report.

By hampering the gene that produces the enzyme, researchers were able to keep mice fed a high-fat diet from gaining weight. The mice also became better at using insulin to process blood sugar, which could lower their odds for developing diabetes.

"The mice were eating normally. It wasn't a food intake effect. They actually had increased energy expenditure," said senior author Dr. Barbara Kahn, vice chair of medicine at Beth Israel Deaconess Medical Center and a professor at Harvard Medical School. "For every calorie they ate, they burned up more energy."

Controlling levels of this enzyme could potentially help people reach and maintain a healthy weight by prompting the body to burn excess energy rather than store it, Kahn suggested.

"Diet and exercise will always be very key, but this opens up the possibility of a new way to speed up cellular metabolism so people don't store as much fat," she said.

Results of animal research do not necessarily apply to humans, however.

Kahn and her colleagues discovered this new role for the enzyme while researching the role of body fat in the development of type 2 diabetes.

Researchers studied thousands of genes present in the fat of mice to determine which ones affected the body's ability to convert glucose (blood sugar) into cellular energy, Kahn said.

See more here:
Obesity-Related Enzyme Targeted in Mouse Study

Drugs used to block copper absorption for a rare genetic condition may find an additional use as a treatment for certain types of cancer, researchers at Duke Medicine report.

The researchers found that cancers with a mutation in the BRAF gene require copper to promote tumor growth. These tumors include melanoma, the most dangerous form of skin cancer that kills an estimated 10,000 people in the United States a year, according to the National Cancer Institute.

"BRAF-positive cancers like melanoma almost hunger for copper," said Christopher M. Counter, Ph.D., professor of Pharmacology & Cancer Biology at Duke University School of Medicine and senior author of the study published April 9, 2014, in Nature.

The BRAF gene is involved in regulating cell division and differentiation. When mutated, the gene causes cells to grow out of control. Using animal models and cells, Counter and colleagues found that when they experimentally inhibited copper uptake by tumors with the BRAF mutation, they could curb tumor growth.

They achieved similar results with drugs used to treat patients with Wilson disease, a genetic disorder in which copper builds up in the tissue, primarily the brain and liver, causing damage.

"Oral drugs used to lower copper levels in Wilson disease could be repurposed to treat BRAF-driven cancers like melanoma, or perhaps even others like thyroid or lung cancer," said Donita C. Brady, Ph.D., lead author of the study.

Already, a clinical trial has been approved at Duke to test the copper-reducing drugs in patients with melanoma, although enrollment has not yet begun: http://1.usa.gov/1qefSJm

"This is a great example of how basic research moves from the laboratory to the clinic," Counter said.

Story Source:

The above story is based on materials provided by Duke Medicine. Note: Materials may be edited for content and length.

Read the original here:
Bad penny: Cancer's thirst for copper can be targeted