Research Roundup: Inactive Drug Ingredients, Whole-Body Regeneration Genes, Alzheimer’s Tests and More
There are plenty of great scientific research stories out this week. Here’s a look at just a few of them.
Inactive Drug Ingredients May Cause Allergic and Adverse Reactions
Researchers at Brigham and Women's Hospital and the Massachusetts Institute of Technology found that the most common drugs in the U.S. have at least one ingredient that can cause an adverse reaction. These inactive ingredients are typically added to improve taste, shelf life, absorption or other improvements. They published their research in the journal Science Translational Medicine.
“When you’re a clinician, the last thing you want to do is prescribe a medication that could cause an adverse reaction or allergic reaction in a patient,” stated corresponding author C. Giovanni Traverso. “This project was inspired by a real-life incident where a patient with Celiac disease was prescribed a medication and the formulation of the pill they picked up from the pharmacy had gluten in it. We wanted to understand the problem and drill down to characterize the entire universe of inactive ingredients across thousands of drugs.”
They analyzed the inactive ingredients in 42,052 oral drugs containing more than 354,597 inactive ingredients. They found that more than 90 percent of all oral medications contained at least one ingredient that can cause allergic or gastrointestinal symptoms in sensitive individuals. These ingredients included lactose, peanut oil, gluten and chemical dyes. They identified 38 inactive ingredients that cause allergic reactions.
Improving Cancer Treatments
Sometimes, patients with cancer cells with identical genomes respond differently to the same treatments. Researchers with IBM and Mount Sinai found that the number of mitochondria in a cell plays a major role in how cancer responds to these drugs. They published their research in the journal Nature Communications.
“Enhancing our understanding of the relationship between mitochondria variability and drug response may lead to more effective targeted cancer treatments, allowing us to find new ways to tackle the problem of drug resistance,” stated Pablo Meyere, Adjunct Assistant Professor of Genetics and Genomic Sciences, at Mount Sinai and Team Leader of Translational Systems Biology at IBM Research.
The group treated different types of cells to six concentrations of a pro-apoptotic drug and measured the number of mitochondria inside the surviving cells. They found that the surviving cells had higher numbers of mitochondria than untreated cells, which suggested that cells with fewer mitochondria are more likely to respond to some drug treatments.
Genes That Control Whole-Body Regeneration
Some animals are capable of growing back limbs or tails, such as salamanders, geckos, and starfish. But some animals, such as planarian worms, jellyfish, and sea anemones can regenerate their entire bodies after being cut in half. Researchers at Harvard University published a paper in the journal Science identifying several DNA switches that control the genes used in whole-body regeneration.
The researchers worked with the three-banded panther worm. “What we found is that this one master gene comes on … and that’s activating genes that are turning on during regeneration,” stated Andrew Gehrke, a post-doctoral fellow in the laboratory of Mansi Srivastava, assistant professor of Organismic and Evolutionary Biology. “Basically, what’s going on is the non-coding regions are telling the coding regions to turn on or off, so a good way to think of it is as though they are switches.”
In order for that process to work, the worms’ DNA, usually tightly folded, has to change so new gene areas can be activated. In order to get to this level of understanding, the researchers had to first sequence the three-banded panther worm’s genome, which is the first from that phylum. In these worms, which are a relatively new-found model for genetic research, Gehrke identified as many as 18,000 regions that change.
Anti-Fungal May Have Applications to Treat Cystic Fibrosis
Individuals with cystic fibrosis (CF) are missing a protein in the lung lining that releases bicarbonate, which is central in fighting infection. CF makes patients susceptible to lung infections. In CF patients, the protein in the cell membrane that allows bicarbonate come to the surface is defective or missing. This protein is called CFTR and the disease is caused by mutations in the CFTR gene.
Researchers with the University of Illinois at Urbana-Champaign investigated the channel-forming properties of an anti-fungal drug, amphotericin, in CF. “Instead of trying to do gene therapy—which is not yet effective in the lung—or to correct the protein, our approach is different,” stated Martin D. Burke, professor of chemistry at Illinois and the associate dean for research at the Carle Illinois College of Medicine. “We use a small molecule surrogate that can perform the channel function of the missing protein, which we call a molecular prosthetic.”
The research, which was published in the journal Nature, found that amphotericin can form channels in the lung tissue’s surface membrane of CF patients. These resulted in bicarbonate being released, bringing down the pH and thickness of the airway surface liquid to normal ranges. These studies were conducted on lung tissue from CF patients. It was also studied in pigs with CF using a type of amphotericin formulated to deliver to the lungs.
Statins Lower Cholesterol, But What Else Can They Do?
Researchers at the University of Toledo, while investigating the side effects of statins, discovered previously unknown benefits. Statins are typically prescribed to lower blood cholesterol. Known side effects are blurred vision, short-term memory loss and increased risk of diabetes. But the research team found it may have an impact on cancer and the immune system. The research was published in the journal Molecular Pharmacology.
The researchers, led by Ajith Karunarathne, assistant professor in the university’s Department of Chemistry and Biochemistry found that statins may play a protective role after a heart attack because they suppress a biological process that disrupts cardiac function. It also suppressed G protein-coupled receptors (GPCRs) and G proteins. GPCR signaling pathways are a major pharmaceutical drug target because they regulate a large number of biological functions, including vision, heart rate and neurotransmission. But another major finding was that statins decreased the ability of migratory cells, such as cancer cells and immune cells, to travel.
“This indicated that GPCR-governed cancer cell migration also can be reduced by statins,” Karunarathne stated.
The Mechanism Linking Heart Disease and Depression
It is fairly common knowledge that depression and heart disease are linked, but the actual mechanism or cause of that connection wasn’t clear. Now, researchers at the University of Cambridge believe they’ve identified inflammation as the link. They published their research in the journal Molecular Psychiatry.
“It is possible that heart disease and depression share common underlying biological mechanisms, which manifest as two different conditions in two different organs—the cardiovascular system and the brain,” stated Golam Khandaker, a Wellcome Trust Intermediate Clinical fellow at the University of Cambridge. “Our work suggests that inflammation could be a shared mechanism for these conditions.”
The researchers used data from the UK Biobank of almost 370,000 middle-aged patients. They evaluated for family history of coronary heart disease associated with risk of major depression and found that people who reported at least one parent dying from a heart attack were 20 percent more likely to develop depression at some time in their life. They then developed a genetic risk score for coronary heart disease based on various genes and markers, looking for indications that would be factors. They found no strong link between the genetic predisposition for heart disease and the likelihood of depression. This suggested the link was something other than genetics.
They then investigated 15 biological markers associated with increased risk of coronary heart disease. They found that triglycerides, and two inflammation markers, IL-6 and CRP, were also risk factors for depression. “Although we don’t know what the shared mechanisms between these diseases are, we now have clues to work with that point towards the involvement of the immune system,” stated Stephen Burgess, a researcher in the group. “Identifying genetic variants that regulate modifiable risk factors helps to find what is actually driving disease risk.”
In particular, the connection between triglyceride levels and depression is puzzling.
Potential Eye Test to Detect Alzheimer’s Disease
Amyloid-beta and tau proteins are both associated with Alzheimer’s disease. Amyloid is typically found early and throughout the disease, while tau proteins appear to accumulate in the brains of patients later in the disease. But researchers at Boston Medical Center have linked low levels of amyloid-beta and tau in the eye fluid with low cognitive scores, which could be a way of testing for early signs of the disease. They published their research in the Journal of Alzheimer’s Disease.
“These findings could help us build an accessible, and minimally invasive test to determine Alzheimer’s disease risk, especially among patients with eye disease,” stated Lauren Wright, an ophthalmology fellow at BMC and first author on the study. “We noted that some of the participants who had low levels of protein biomarkers in their eye fluid already had signs of mild to moderate dementia based on their cognitive scores.”
Earlier research has shown a link between low levels of amyloid-beta and tau in cerebral spinal fluid and preclinical Alzheimer’s. However, a lumbar puncture is both expensive and inconvenient, and is unlikely to ever become a routine prescreening test. In this research, the team took samples of eye fluid from 80 patients previously scheduled for eye surgery. Typically, the fluid drawn during these procedures is discarded. The scientists tested the eye fluid to determine amyloid and tau levels and correlated them to a baseline cognitive test.