Nature’s Medicine Cabinet

More than 70 percent of new drugs approved within the past 30 years originated from trees, sea creatures and other organisms that produce substances they need to survive. Since ancient times, people have been searching the Earth for natural products to use—from poison dart frog venom for hunting to herbs for healing wounds. Today, scientists are modifying them in the laboratory for our medicinal use. Here’s a peek at some of the products in nature’s medicine cabinet.

Vampire bat

A protein called draculin found in the saliva of vampire bats is in the last phases of clinical testing as a clot-buster for stroke patients. Vampire bats are able to drink blood from their victims because draculin keeps blood from clotting. The first phases of clinical trials have shown that the protein’s anti-coagulative properties could give doctors more time to treat stroke patients and lower the risk of bleeding in the brain.

Sea squirts

Sea squirts in the crystal waters of West Indies coral reefs and mangrove swamps are the source of an experimental cancer drug called Yondelis. The drug binds to DNA and damages specific genes, which slows cancer cell division, growth and spread. The first set of clinical studies has shown that the drug is safe for use in humans. Additional phases of clinical testing are underway to evaluate whether Yondelis effectively treats tumors of the muscles, tendons, supportive tissues and other types of cancer.

Gila monster

A hormone found in the saliva of the gila monster, a venomous lizard from the woodlands and deserts of the American Southwest, was modified to help people with type 2 diabetes maintain healthy blood sugar levels. Since gila monsters only eat about twice a year, their sugar storage hormone is active for much longer than insulin is in humans. The hormone-derived drug, Byetta, also slows the movement of food from the stomach into the small intestine, which often results in weight loss in diabetics.

Guggul tree

The guggul tree is native to India and has been used in Ayurvedic medicine since at least 600 B.C. to treat obesity and lipid disorders. Scientists are conducting preliminary studies to explore the cholesterol-lowering properties of guggulsterone, a compound in the sap of the guggul tree. Researchers think guggulsterone blocks receptors in liver cells and alters cholesterol break down. Studies have also suggested that guggulsterone has anti-inflammatory properties and can lower triglyceride levels.

Cinchona tree

The bark of the cinchona tree, found in the Amazon rainforest, is the source of the antimalarial drug quinine. Isolated by French chemists in the early 19th century, quinine treats malaria by altering the life cycle of the malaria parasite. Since then, scientists have designed other antimalarial drugs including chloroquine, mefloquine and other derivatives that are chemically similar to quinine. Another natural product, sweet wormwood plant, is the basis of the malarial treatment artemisinin.

Yew tree

A chemical produced by the Pacific yew tree is now the cancer-treating drug paclitaxel (Taxol). The plant-derived drug works by inhibiting the function of microtubules, structural elements that are needed for cell division. By preventing cancer cells from dividing, Taxol stops the cancer from growing. Taxol is used to treat a variety of cancers including breast, lung, prostate and ovarian cancer.

Cone snail

Cone snails in the waters near Australia, Indonesia and the Philippines have toxin-packed venom that’s being studied as a treatment for chronic pain. Prialt, a synthetic compound modeled after a toxin in the venom, is 1,000 times more powerful than morphine in treating certain kinds of chronic pain. The snail-derived drug jams nerve transmission in the spinal cord and blocks certain pain signals from reaching the brain. It’s prescribed to help manage the pain of people suffering from multiple sclerosis, AIDS and cancer.

Bishop’s weed

Psoralen, derived from a Nile-dwelling plant called Bishop’s weed, is a key component of photodynamic therapy, which is used to treat several cancers. Once activated by light, psoralen attaches tenaciously to the DNA of rapidly dividing cancer cells and kills them. Psoralen is also prescribed to increase the ultraviolet absorptivity of skin so UV light can then be used to treat severe skin conditions like psoriasis and eczema.

Snowdrops

Galantamine, a compound extracted from the bulbs and flowers of daffodils, spider lilies and snowdrops, is prescribed to stabilize and improve cognitive function in Alzheimer’s patients. It works by preventing the breakdown of acetylcholine, a chemical that sends messages between certain nerve cells and is important for learning and memory.

The vampire bat, gila monster, bishop’s weed and snowdrop images courtesy of iStock; Sea squirt image courtesy of Pharmamar; Commiphora wightii (guggul tree) Exit icon image courtesy of Vinayaraj V R under CC BY SA 3.0; Cone snail image courtesy of Kerry Matz, University of Utah; Cinchona tree Exit icon image courtesy of U.S. Geological Survey; Pacific yew tree image courtesy of Virginia Tech, Department of Forest Resources and Environmental Conservation.

Data-Mining Study Explores Health Outcomes from Common Heartburn Drugs

Results of a data-mining study suggest a link between a common heartburn drug and heart attacks. Credit: Stock image.

Scouring through anonymized health records of millions of Americans, data-mining scientists found an association between a common heartburn drug and an elevated risk for heart attacks. Their preliminary results suggest that there may be a link between the two factors.

For 60 million Americans, heartburn is a painful and common occurrence caused by stomach acid rising through the esophagus. It’s treated by drugs such as proton-pump inhibitors (PPIs) that lower acid production in the stomach. Taken by about one in every 14 Americans, PPIs, which include Nexium and Prilosec, are the most popular class of heartburn drugs.

PPIs have long been thought to be completely safe for most users. But a preliminary laboratory study published in 2013 suggested that this may not be the case. The study, led by a team of researchers at Stanford University, showed that PPIs could affect biochemical reactions outside of their regular acid suppression action that would have harmful effects on the heart.

To find out if people who took these drugs were more likely to have a heart attack, a bioinformatics team led by Nigam Shah of the Stanford University School of Medicine used data-mining techniques that were previously tested to comb through anonymized electronic medical records of 2.9 million people.

The results, published in PLOS ONE on June 10, suggest a link between PPI use and elevated risk of heart attacks, regardless of the age of the user. The researchers didn’t find a link between another widely used family of heartburn drugs, H2 blockers, and heart attacks.

It is important to note that the results suggest only an association, not a cause-and-effect relationship—many other variables may contribute. “The association we found with PPI use and increased chances of a subsequent heart attack doesn’t in and of itself prove causation,” explains Shah in a Stanford news release Exit icon about the work.

To further explore the results, Shah and colleagues have initiated pre-clinical studies to quantify the extent to which PPIs may modify the biochemical reactions that affect vascular health.

“This research shows the value of mining large amounts of medical data that are already collected and using that information as a springboard to make new discoveries,” says NIGMS’ Rochelle Long.

It also provides an example of how a combination of experimental and data-mining studies can be used to explore, detect and analyze adverse drug events.

This work was funded in part by NIH grants R01GM101430 and U54HG004028.

From Basic Research to Bioelectronic Medicine

Kevin Tracey
Kevin J. Tracey of the Feinstein Institute for Medical Research, the research branch of the North Shore-LIJ Health System, helped launch a new discipline called bioelectronic medicine. Credit: North Shore-LIJ Studios.

By showing that our immune and nervous systems are connected, Kevin J. Tracey Exit icon of the North Shore-LIJ Health System’s Feinstein Institute for Medical Research helped launch a new discipline called bioelectronic medicine. In this field, scientists explore how to use electricity to stimulate the body to produce its own disease-fighting molecules.

I spoke with Tracey about his research, the scientific process and where bioelectronic medicine is headed next.

How did you uncover the connection between our immune and nervous systems?

My lab was testing whether a chemical we developed called CNI-1493 could stop immune cells from producing inflammation-inducing molecules called TNFs in the brain of rats during a stroke. It does. But we were surprised to find that this chemical also affects neurons, or brain cells. The neurons sense the chemical and respond by sending an electrical signal along the vagus nerve, which runs from the brain to the internal organs. The vagus nerve then releases molecules that tell immune cells throughout the body to make less TNF. I’ve named this neural circuit the inflammatory reflex. Today, scientists in bioelectronic medicine are exploring ways to use tiny electrical devices to stimulate this reflex to treat diseases ranging from rheumatoid arthritis to cancer. Continue reading

Designing Drugs That Kill Invasive Fungi Without Harming Humans

Top to bottom: Cryptococcus, Candida, Aspergillus, Pneumocystis
Invasive fungal infections kill more than 1 million people worldwide every year. Almost all of these deaths are due to fungi in one of these four groups. Credit: Centers for Disease Control and Prevention.

Invasive fungal infections—the kind that infect the bloodstream, lung and brain—are inordinately deadly. A big part of the problem is the lack of drugs that are both effective against the fungi and nontoxic to humans.

The situation might change in the future though, thanks to the work of a multidisciplinary research team led by chemist Martin Burke at the University of Illinois. For years, the team has focused on an antifungal agent called amphotericin B (AmB for short). Although impressively lethal to fungi, AmB is also notoriously toxic to human cells.

Most recently, the research team chemically modified the drug to create compounds that kill fungi, but don’t disrupt human cells. The scientists explain it all in the latest issue of Nature Chemical Biology.

Invasive fungal infections are so intractable because most antifungal drugs aren’t completely effective. Plus, fungi have a tendency to develop resistance to them. AmB is a notable exception. Isolated 50 years ago from Venezuelan dirt, AmB has evaded resistance and remains highly effective. Unfortunately, it causes side effects so debilitating that some doctors call it “ampho-terrible.” At high doses, it is fatal.

For decades, scientists believed that AmB molecules kill fungal cells by forming membrane-piercing pores, or ion channels, through which the cells’ innards leak out. Last year, Burke’s group overturned this well-established concept using evidence from nuclear magnetic resonance, chemistry and cell-based experiments. The researchers showed that AmB molecules assemble outside cells into lattice-like structures. These structures act as powerful sponges, sucking vital lipid molecules, called ergosterol, right out of the fungal cell membrane, destroying the cell. Continue reading

Scientists Shine Light on What Triggers REM Sleep

Illustration of a brain.

While studying how the brain controls REM sleep, researchers focused on areas abbreviated LDT and PPT in the mouse brainstem. This illustration shows where these two areas are located in the human brain. Credit: Wikimedia Commons. View larger image

Has the “spring forward” time change left you feeling drowsy? While researchers can’t give you back your lost ZZZs, they are unraveling a long-standing mystery about sleep. Their work will advance the scientific understanding of the process and could improve ways to foster natural sleep patterns in people with sleep disorders.

Working at Massachusetts General Hospital and MIT, Christa Van Dort Exit icon, Matthew Wilson Exit icon and Emery Brown Exit icon focused on the stage of sleep known as REM. Our most vivid dreams occur during this period, as do rapid eye movements, for which the state is named. Many scientists also believe REM is crucial for learning and memory.

REM occurs several times throughout the night, interspersed with other sleep states collectively called non-REM sleep. Although REM is clearly necessary—it occurs in all land mammals and birds—researchers don’t really know why. They also don’t understand how the brain turns REM on and off. Continue reading

Meet Maureen L. Mulvihill

Maureen L. Mulvihill, Ph.D.
Credit: Actuated Medical, Inc.
Maureen L. Mulvihill, Ph.D.
Fields: Materials science, logistics
Works at: Actuated Medical, Inc., a small company that develops medical devices
Second job (volunteer): Bellefonte YMCA Swim Team Parent Boost Club Treasurer
Best skill: Listening to people
Last thing she does every night: Reads to her 7- and 10-year-old children until “one of us falls asleep”

If you’re a fan of the reality TV show Shark Tank, you tune in to watch aspiring entrepreneurs present their ideas and try to get one of the investors to help develop and market the products. Afterward, you might start to think about what you could invent.

Maureen L. Mulvihill has never watched the show, but she lives it every day. She is co-founder, president and CEO of Actuated Medical, Inc. (AMI), a Pennsylvania-based company that develops specialized medical devices. The devices include a system for unclogging feeding tubes, motors that assist MRI-related procedures and needles that gently draw blood.

AMI’s products rely on the same motion-control technologies that allow a quartz watch to keep time, a microphone to project sound and even a telescope to focus on a distant object in a sky. In general, the devices are portable, affordable and unobtrusive, making them appealing to doctors and patients.

Mulvihill, who’s trained in an area of engineering called materials science, says, “I’m really focused on how to translate technologies into ways that help people.” Continue reading

A Bright New Method for Rapidly Screening Cancer Drugs

Illustration of red, green and blue fluorescent proteins.
Chemists have devised a new approach to screening cancer drugs that uses gold nanoparticles with red, green and blue outputs provided by fluorescent proteins. Credit: University of Massachusetts Amherst.

Scientists may screen billions of chemical compounds before uncovering the few that effectively treat a disease. But identifying compounds that work is just the first step toward developing a new therapy. Scientists then have to determine exactly how those compounds function.

Different cancer therapies attack cancer cells in distinct ways. For example, some drugs kill cancer cells by causing their outer membranes to rapidly rupture in a process known as necrosis. Others cause more subtle changes to cell membranes, which result in a type of programmed cell death known as apoptosis.

If researchers could distinguish the membrane alterations of chemically treated cancer cells, they could quickly determine how that chemical compound brings about the cells’ death. A new sensor developed by a research team led by Vincent Rotello Exit icon of the University of Massachusetts Amherst can make these distinctions in minutes. Continue reading

New Streamlined Technique for Processing Biological Samples

Illustration of Slug flow microextraction.
Researchers have discovered a faster, easier and more affordable technique for processing biological samples. Credit: Weldon School of Biomedical Engineering, Purdue University.

It’s not unusual for the standard dose of a drug to work well for one person but be less effective for another. One reason for such differences is that individuals can break down drugs at different rates, leading to different concentrations of drugs and of their breakdown products (metabolites) in the bloodstream. A promising new process Exit icon called slug-flow microextraction could make it faster, easier and more affordable to regularly monitor drug metabolites so that medication dosages could be tailored to each patient’s needs, an approach known as personalized medicine. This technique could also allow researchers to better monitor people’s responses to new drug treatments during clinical trials. Continue reading

Outwitting Antibiotic Resistance

Marine scene with fish and corals
The ocean is a rich source of microbes that could yield infection-fighting natural molecules. Credit: National Oceanic and Atmospheric Administration Exit icon.

Antibiotics save countless lives and are among the most commonly prescribed drugs. But the bacteria and other microbes they’re designed to eradicate can evolve ways to evade the drugs. This antibiotic resistance, which is on the rise due to an array of factors, can make certain infections difficult—and sometimes impossible—to treat.

Read the Inside Life Science article to learn how scientists are working to combat antibiotic resistance, from efforts to discover potential new antibiotics to studies seeking more effective ways of using existing ones.

 

New Research Sheds Light on Drug-Induced Salivary Issues

Open human mouth
Scientists have discovered a possible mechanism behind the bad taste and dry mouth caused by some drugs. Credit: Stock image.

The effects some medicines have on our salivary glands can at times extend beyond the fleeting flavor we experience upon ingesting them. Sometimes drugs cause a prolonged bad taste or dryness in the mouth, both of which can discourage people from taking medicines they need. Now, a research team led by Joanne Wang of the University of Washington has discovered a possible mechanism behind this phenomenon. Working primarily with mice and using a commonly prescribed antidiabetic drug known to impair taste, the scientists identified a protein in salivary gland cells that takes up the drug from the bloodstream and secretes it in saliva. Wang and her colleagues were also able to pinpoint a specific gene that, when removed, hindered this process. They hope their new insights will aid efforts to develop medicines that do not cause salivary issues.

This work also was funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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