Category Archives: Transhuman News

PUBLIC RELEASE DATE:

12-Nov-2014

Contact: Julia Evangelou Strait straitj@wustl.edu 314-286-0141 Washington University School of Medicine @WUSTLmed

Rare mutations that shut down a single gene are linked to lower cholesterol levels and a 50 percent reduction in the risk of heart attack, according to new research from Washington University School of Medicine in St. Louis, the Broad Institute at Massachusetts Institute of Technology and Harvard, and other institutions.

The gene, called NPC1L1, is of interest because it is the target of the drug ezetimibe, often prescribed to lower cholesterol.

The study appears Nov. 12 in The New England Journal of Medicine.

Everyone inherits two copies of most genes -- one copy from each parent. In the study, the researchers found that people with one inactive copy of NPC1L1 appeared to be protected against high LDL cholesterol --the so-called "bad" cholesterol -- and coronary heart disease, a narrowing of the heart's arteries that can lead to heart attacks.

"This analysis demonstrates that human genetics can guide us in terms of thinking about appropriate genes to target for clinical therapy," said first author Nathan O. Stitziel, MD, PhD, a cardiologist at Washington University School of Medicine. "When people have one copy of a gene not working, it's a little like taking a drug their entire lives that is inhibiting this gene."

The investigators mined genetic data from large clinical trials to find individuals with naturally occurring mutations in the NPC1L1 gene that completely shut it down. They analyzed multiple existing studies, pooling data from about 113,000 people. Of these trial participants, only 82 were found to have a mutation that shut off one copy of the NPC1L1 gene. No one had two inactive copies of NPC1L1. Based on a subset of data in the analysis, the researchers estimate roughly 1 in 650 people carry one inactive version of the gene.

The investigators found that people with only one working copy of the gene had LDL cholesterol levels an average of 12 milligrams per deciliter lower than the wider population of people with two working copies of the gene. This approximately 10 percent reduction in LDL cholesterol is comparable to that seen in patients taking ezetimibe. But beyond simply lowering cholesterol, the 82 people with inactive copies also had about half the risk of coronary heart disease as people with two functional copies of the gene.

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Errors in single gene may protect against heart disease

PUBLIC RELEASE DATE:

13-Nov-2014

Contact: Matt Solovey msolovey@hmc.psu.edu 717-531-8606 Penn State @penn_state

Mice bred to carry a gene variant found in a third of ALS patients have a faster disease progression and die sooner than mice with the standard genetic model of the disease, according to Penn State College of Medicine researchers. Understanding the molecular pathway of this accelerated model could lead to more successful drug trials for all ALS patients.

Amyotrophic lateral sclerosis, commonly known as Lou Gehrig's disease, is a degeneration of lower and upper motor neurons in the brainstem, spinal cord and the motor cortex. The disease, which affects 12,000 Americans, leads to loss of muscle control. People with ALS typically die of respiratory failure when the muscles that control breathing fail.

Penn State researchers were the first to discover increased iron levels in the brains of some patients with the late-onset neurodegenerative disorders Parkinson's disease and Alzheimer's disease. A decade ago, they also identified a relationship between ALS and excess iron accumulation when they found that 30 percent of ALS patients in their clinic carried a variant of a gene known as HFE that is associated with iron overload disease.

For this study, the researchers crossbred mice with the HFE gene variant with the standard mice used in ALS research.

"When we followed the disease progression and the behavior of our crossbred mice compared to the standard mice, we saw significant differences," said James Connor, vice chair of neurosurgery research and director of the Center for Aging and Neurodegenerative Diseases. The crossbred mice performed significantly worse on tests of forelimb and hindlimb grip strength and had a 4 percent shorter life span. The researchers published their findings in BBA Molecular Basis of Disease.

"The disease progression was much faster in the crossbred mice than in the standard mice," Connor said. "What we found is that when ALS happens in the presence of the HFE gene variant, things go downhill more quickly."

The lead investigator on this project, graduate student Wint Nandar, noticed that the HFE gene variant sped up disease progression and death in females but not males. Males with ALS die faster, on average, than females.

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Genotype found in 30 percent of ALS patients speeds up disease progression

Published November 13, 2014

Scientists have discovered gene mutations that give people naturally lower cholesterol levels and cut their risk of heart disease in half.

That discovery may have a big implication: A blockbuster drug that mimics these mutations has long been sold without evidence that it cuts the chance of heart disease. Results of a large study that looked for that evidence will be revealed on Monday.

The drug is Merck & Co.'s Zetia, also sold in combination with another medicine as Vytorin.

When Zetia was designed, scientists knew how it worked to lower LDL, or bad cholesterol, and it won federal approval based on its ability to do that. But the existence of gene mutations that could do the same thing was not known, nor was it known if lowering cholesterol this way would translate to a lower risk of heart problems.

The new research gives a biological basis to suggest the drug could help.

Researchers found that people with mutations in a gene called NPC1L1 had LDL that was 12 milligrams per deciliter lower on average than others without a mutation. That is similar to how much Zetia lowers LDL.

The bigger finding was that the gene mutations lowered the risk of heart disease by 53 percent.

"It's a stunner," said Dr. Eric Topol, director of the Scripps Translational Science Institute in La Jolla, California. "We're learning more and more about protective mutations," and the effect these had on heart disease risk was far greater than the degree to which they lowered cholesterol, he said.

Topol had no role in the study, which was led by researchers from the Washington University School of Medicine in St. Louis, the Broad Institute at the Massachusetts Institute of Technology and Harvard, and other institutions. Results were published online Wednesday by the New England Journal of Medicine.

Read more:
Gene mutation discovery boosts interest in heart drug