Every person’s genetic blueprint, or genome, is unique because of variations that occasionally occur in our DNA sequences. Most of those are passed on to us from our parents. But not all variations are inherited—each of us carries 60 to 100 “new mutations” that happened for the first time in us. Some of those variations can knock out the function of a gene in ways that lead to disease or other serious health problems, particularly in people unlucky enough to have two malfunctioning copies of the same gene. Recently, scientists have begun to identify rare individuals who have loss-of-function variations that actually seem to improve their health—extraordinary discoveries that may help us understand how genes work as well as yield promising new drug targets that may benefit everyone.
In a study published in the journal Nature, a team partially funded by NIH sequenced all 18,000 protein-coding genes in more than 10,500 adults living in Pakistan . After finding that more than 17 percent of the participants had at least one gene completely “knocked out,” researchers could set about analyzing what consequences—good, bad, or neutral—those loss-of-function variations had on their health and well-being.
Tags: All of Us, All of Us Research Program, APOC3, cardiology, cholesterol, DNA, drug development, drug targets, gene knockouts, gene mutations, genetics, genomics, heart attack, heart disease, human knockout, myocardial infarction, Pakistan, Pakistan Rise of Myocardial Infarction Study, PLA2G7, triglycerides
When you think of the causes of infectious diseases, what first comes to mind are probably viruses and bacteria. But parasites are another important source of devastating infection, especially in the developing world. Now, NIH researchers and their collaborators have discovered a new kind of treatment that holds promise for fighting parasitic roundworms. A bonus of this result is that this same treatment might work also for certain deadly kinds of bacteria.
The researchers identified the potential new therapeutic after testing more than a trillion small protein fragments, called cyclic peptides, to find one that could disable a vital enzyme in the disease-causing organisms, but leave similar enzymes in humans unscathed. Not only does this discovery raise hope for better treatments for many parasitic and bacterial diseases, it highlights the value of screening peptides in the search for ways to treat conditions that do not respond well—or have stopped responding—to more traditional chemical drug compounds.
Tags: anthrax, antibiotic resistance, Bacillus anthracis, bacteria, cell biology, chemistry, cofactor-independent phosphoglycerate mutase, cyclic peptides, drug design, drug development, drug discovery, drug targets, drugs, glycolysis, ipglycermides, iPGM, parasite, peptide, roundworm, small molecules, Staphylococcus aureus
People with type 2 diabetes are at increased risk for heart attacks, stroke, and other forms of cardiovascular disease, and at an earlier age than other people. Several years ago, the Food and Drug Administration (FDA) recommended that drug developers take special care to show that potential drugs to treat diabetes don’t adversely affect the cardiovascular system . The challenge in implementing that laudable exhortation is that a drug’s long-term health risks may not become clear until thousands or even tens of thousands of people have received it over the course of many years, sometimes even decades.
Now, a large international study, partly funded by NIH, offers some good news: proof-of-principle that “Big Data” tools can help to identify a drug’s potential side effects much earlier in the drug development process . The study, which analyzed vast troves of genomic and clinical data collected over many years from more than 50,000 people with and without diabetes, indicates that anti-diabetes therapies that lower glucose by targeting the product of a specific gene, called GLP1R, are unlikely to boost the risk of cardiovascular disease. In fact, the evidence suggests that such drugs might even offer some protection against heart disease.
Tags: anti-diabetes drugs, big data, cardiovascular disease, diabetes, diabetic heart disease, drug benefits, drug development, drug side effects, drug targets, genetic variant, genomics, GlaxoSmithKline, GLP1R, heart disease, investigational drugs, liraglutide, Mendelian randomization, PMI, precision medicine, Precision Medicine Initiative cohort, T2D, type 2 diabetes, Victoza
The proteins speckling the surface of a cancer cell reveal critical clues—the type of cancer cell and a menu of possible mutations that may have triggered the malignancy. Since these proteins are exposed on the outside of the cell, they are also ideal targets for so-called precision cancer therapies (especially monoclonal antibodies), optimized for the particular individual. But in the past, to analyze and identify these different proteins, large samples of tissue have been needed. Typically, these are derived from surgical biopsies. But biopsies are expensive and invasive. Furthermore, they aren’t a practical option if you want to monitor the effects of a drug in a patient closely over time.
Using a minimally invasive method of cell sampling called fine needle aspiration, physicians can collect miniscule cell samples frequently, cheaply, and safely. But, until now, these tiny samples only provided enough material to analyze a handful of cell surface proteins. So, it comes as particularly good news that NIH-funded researchers at Massachusetts General Hospital in Boston have developed a new technology that quickly identifies hundreds of these proteins simultaneously, using just a few of the patient’s cells . The key to this new method is a clever adaptation of the familiar barcode.
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