Archive for the ‘University of Iowa Hospitals and Clinics’ Category

by Jennifer Brown

The recent Ebola outbreak in West Africa has claimed more than 11,300 lives—a stark reminder of the lack of effective options for treating or preventing the disease.

Progress has been made on developing vaccines, but there is still a need for antiviral therapies to protect health care workers and local populations in the event of future outbreaks.

Now, a new study suggests that gamma interferon, an FDA-approved drug, may have potential as an antiviral therapy to prevent Ebola infection when given either before or after exposure to the virus.

The findings, published in the journal PLOS Pathogens, show that gamma interferon, given up to 24 hours after exposure, inhibits Ebola infection in mice and completely protects the animals from death.

Ebola infection appears to be a stepwise process. First, the virus targets and infects macrophages or dendritic cells, two types of immune system cells found in the liver, spleen, and lymph nodes. Ebola then replicates in those cells. Following this initial infection, which happens at day 3 or 4 in non-human primates, Ebola virus is released into the blood and infects a plethora of other different cell populations.

“It goes from an early stage with a very targeted infection of only these few cell types, to everything being infected,” says Wendy Maury, professor of microbiology at the University of Iowa.

“We think what’s happening with gamma interferon is that it’s targeting macrophages and blocking the infection of those initial cell targets so you don’t get the second round of infection.”

The University of Iowa does not have a specializing BioSafety Level 4 (BSL4) lab that is required for experiment using Ebola virus, so the researchers made their initial findings using a surrogate virus, which targets and infects the same cells as Ebola, but does not cause the disease.

This Ebola lookalike—a sheep in wolf’s clothing—consists of a less dangerous vesicular stomatitis virus (VSV) that expresses Ebola glycoproteins on its surface.

All of the results found using the surrogate virus were then repeated using mouse-adapted Ebola virus in the BSL4 lab of Maury’s longtime collaborator Robert Davey at Texas Biomedical Institute in San Antonio, Texas.

Gamma interferon inhibits the virus’s ability to infect human and mouse macrophages, in part by blocking virus replication in the cells. Pre-treating mice with interferon gamma 24 hours before exposure protects the animals from infection and death. The researchers were surprised to find that treatment up to 24 hours after what would have been a lethal exposure also completely protected the animals from death, and they could no longer detect any Ebola virus in the mouse’s cells.

The findings suggest that interferon gamma may be useful both as a prophylaxis and post-exposure treatment against Ebola. The team still has to determine how late gamma interferon can be given to the mice and still prevent infection. However, the results suggest a window of time after exposure when gamma interferon may be an effective antiviral therapy.

“My guess is that if you delay the gamma interferon too much, you miss this window of opportunity to block the infection in macrophage cells and the gamma interferon can no longer provide protection,” Maury says.

Maury and colleagues investigated how gamma interferon might be helping the cells fight off the Ebola virus. They identified that the expression of more than 160 genes in human macrophages is stimulated by gamma interferon. Introduction of some of these genes into cells was sufficient to prevent Ebola infection.

“This mechanistic information might suggest more precise drug targets rather than the broad effects, including adverse side-effects, that are produced by gamma-interferon,” she says.

Gamma interferon is already approved by the FDA to treat chronic granulomatous disease (an immune disease) and severe malignant osteopetrosis.

In addition to moving the studies into larger animal models, Maury next plans to study the ability of gamma interferon to inhibit Ebola infection in conjunction with other developing antivirals.

“Right now, there are no FDA-approved antiviral therapies for Ebola, but there are some being developed that target virus entry,” she says. “We know that gamma interferon blocks replication but not entry into cells. So combining an entry inhibitor with gamma interferon may allow us to reduce amount of gamma interferon needed and target two different steps in the virus’s life cycle, which has been shown in HIV to be critically important for controlling the virus.”

http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005263

http://now.uiowa.edu/2015/12/fda-approved-drug-protects-mice-ebola

A placenta sustained you and every person ever born for 9 months, serving as your lungs and kidneys and pumping out hormones while you developed in the womb. Problems with this disk-shaped mass of tissue can contribute to everything from preterm births to diseases of middle age. Yet when a baby is born, hospitals usually throw the placenta away.

“It’s the least understood human organ,” says Alan Guttmacher, director of the National Institute of Child Health and Human Development (NICHD) in Bethesda, Maryland. “A large part of the scientific community never thinks about the placenta at all.” He and others hope to change that, however, by rallying researchers and funders, including other parts of the National Institutes of Health (NIH), around an effort to better understand the underappreciated organ. At an NICHD-sponsored workshop last week, some 70 researchers laid out their ideas for what NICHD calls the Human Placenta Project, including ways to better monitor the placenta during a pregnancy, and drugs to bolster it when it falters.

The human placenta forms primarily from cells that develop from the outer layer of fetal cells that surround an early embryo. Early in pregnancy, these trophoblasts invade the uterine wall and later develop a complex network of tiny projections called villi, which contain fetal blood vessels. This treelike structure of villi absorbs oxygen and nutrients from maternal blood; fetal waste and carbon dioxide meanwhile diffuse into the maternal bloodstream. Other specialized cells link the developing placenta to the umbilical cord. To avoid rejection by the mother’s immune system, the placenta employs various tricks, such as not expressing certain proteins. The placenta’s role during pregnancy is “an incredibly interesting biological time” that offers lessons for everything from cancer to organ transplantation, says physician-scientist Kimberly Leslie of the University of Iowa in Iowa City.

A malfunctioning, too small, or weakly attached placenta can starve the fetus, stunting its growth, and can also contribute to preeclampsia, or pregnancy-related high blood pressure, a condition that occurs in up to 6% of pregnancies and can require premature delivery of a baby. Adult diseases, too, ranging from cardiovascular disease to insulin resistance, seem to be linked to abnormal placenta morphology for poorly understood reasons.

During recent strategic planning at NICHD, researchers concluded that the placenta deserved closer study. “It came up repeatedly,” Guttmacher says. He expects that the Human Placenta Project will focus on understanding both the normal and abnormal placenta in real time during the course of pregnancy. It will also look for possible interventions—for example, a drug that would spur the growth of an abnormally small placenta.

Some at the workshop hope to adapt ultrasound and magnetic resonance imaging techniques now used to study the heart and brain to measure blood flow and oxygenation in the placenta. Injecting tracers, however, may be sensitive ethical territory. “People are very scared of doing things to pregnant women,” said placenta researcher Nicholas Illsley, of Hackensack University Medical Center in New Jersey, at the meeting. Another idea is to probe the mother’s bloodstream for cells and nucleic acids shed by the placenta as a window into the function of the organ.

Researchers also mused about creating a “placenta on a chip” that would mimic the tissue in the lab or developing molecular sensors that could monitor the placenta throughout pregnancy. “This sounds like science fiction, but if you showed me an iPhone 20 years ago, I would have said this was science fiction,” said Yoel Sadovsky, of the Magee-Womens Research Institute in Pittsburgh, Pennsylvania, at the meeting.

Attendees described a few immediate goals. One is to come up with standard definitions of a normal and abnormal placenta. Placenta morphology varies widely, and those from a healthy pregnancy can still have visible abnormalities, whereas those from sick babies often look completely normal, says systems biologist Brian Cox of the University of Toronto in Canada. Even before the NICHD meeting, the international community of placenta researchers had begun to coordinate their efforts by planning a website that will list existing placenta biobanks and help match collaborators.

At a time when NICHD’s budget is flat, money could be a limiting factor for the Human Placenta Project, which Guttmacher hopes will fund its first grants in 2016 and go for a decade or more. He expects that in addition to setting aside new money for the project, NICHD may give extra weight to high-quality grant applications focusing on the placenta. NICHD’s own contribution may be only “in the millions” of dollars, Guttmacher says. But he says eight other NIH institutes have expressed interest in contributing, as has the March of Dimes, an organization long focused on maternal and infant health. At long last, a throwaway organ may get the attention it deserves.

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.

http://news.sciencemag.org/biology/2014/06/nih-gears-closer-look-human-placenta

Scientists probing the link between depression and a hormone that controls hunger have found that the hormone’s antidepressant activity is due to its ability to protect newborn neurons in a part of the brain that controls mood, memory, and complex eating behaviors. Moreover, the researchers also showed that a new class of neuroprotective molecules achieves the same effect by working in the same part of the brain, and may thus represent a powerful new approach for treating depression.

“Despite the availability of many antidepressant drugs and other therapeutic approaches, major depression remains very difficult to treat,” says Andrew Pieper, associate professor of psychiatry and neurology at the University of Iowa Carver College of Medicine and Department of Veterans Affairs, and co-senior author of the study.

In the new study, Pieper and colleagues from University of Texas Southwestern Medical Center led by Jeffrey Zigman, associate professor of internal medicine and psychiatry at UT Southwestern, focused on understanding the relationship between depression, the gut hormone ghrelin, and the survival of newborn neurons in the hippocampus, the brain region involved in mood, memory, and eating behaviors.

“Not only did we demonstrate that the P7C3 compounds were able to block the exaggerated stress-induced depression experienced by mice lacking ghrelin receptors, but we also showed that a more active P7C3 analog was able to complement the antidepressant effect of ghrelin in normal mice, increasing the protection against depression caused by chronic stress in these animals,” Zigman explains.

“The P7C3 compounds showed potent antidepressant activity that was based on their neurogenesis-promoting properties,” Pieper adds. “Another exciting finding was that our experiments showed that the highly active P7C3 analog acted more rapidly and was more effective [at enhancing neurogenesis] than a wide range of currently available antidepressant drugs.”

The findings suggest that P7C3-based compounds may represent a new approach for treating depression. Drugs based on P7C3 might be particularly helpful for treating depression associated with chronic stress and depression associated with a reduced response to ghrelin activity, which may occur in conditions such as obesity and anorexia nervosa.

Future studies, including clinical trials, will be needed to investigate whether the findings are applicable to other forms of depression, and determine whether the P7C3 class will have antidepressant effects in people with major depression.

The hippocampus is one of the few regions in the adult brain where new neurons are continually produced – a process known as neurogenesis. Certain neurological diseases, including depression, interfere with neurogenesis by causing death of these new neurons, leading to a net decrease in the number of new neurons produced in the hippocampus.

Ghrelin, which is produced mainly by the stomach and is best known for its ability to stimulate appetite, also acts as a natural antidepressant. During chronic stress, ghrelin levels rise and limit the severity of depression caused by long-term stress. When mice that are unable to respond to ghrelin experience chronic stress they have more severe depression than normal mice.

In the new study, Pieper and Zigman’s team showed that disrupted neurogenesis is a contributing cause of depression induced by chronic stress, and that ghrelin’s antidepressant effect works through the hormone’s ability to enhance neurogenesis in the hippocampus. Specifically, ghrelin helps block the death of these newborn neurons that otherwise occurs with depression-inducing stress. Importantly, the study also shows that the new “P7C3-class” of neuroprotective compounds, which bolster neurogenesis in the hippocampus, are powerful, fast-acting antidepressants in an animal model of stress-induced depression. The results were published online April 22 in the journal Molecular Psychiatry.

Potential for new antidepressant drugs

The neuroprotective compounds tested in the study were discovered about eight years ago by Pieper, then at UT Southwestern Medical Center, and colleagues there, including Steven McKnight and Joseph Ready. The root compound, known as P7C3, and its analogs protect newborn neurons from cell death, leading to an overall increase in neurogenesis. These compounds have already shown promising neuroprotective effects in models of neurodegenerative disease, including Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and traumatic brain injury. In the new study, the team investigated whether the neuroprotective P7C3 compounds would reduce depression in mice exposed to chronic stress, by enhancing neurogenesis in the hippocampus.

http://now.uiowa.edu/2014/04/protecting-new-neurons-reduces-depression-caused-stress

A new study has found that a compound in green tomatoes, tomatidine, not only boosts muscle growth and strength, it protects against muscle wasting caused by illness, injury or aging. A research team at the University of Iowa found that healthy mice given supplements containing tomatidine grew bigger muscles, became stronger and could exercise longer. Even better, the mice did not gain any weight due to a corresponding loss of fat, suggesting that the compound may also have potential for treating obesity. Nice bonus.

The research team used a systems biology tool called the Connectivity Map to identify tomatidine and discovered it stimulated growth of cultured human muscle cells. (The same screening method previously identified a compound in apple peel as a muscle-boosting agent – but green tomatoes were found to be even more potent.) In fact, the team discovered that tomatidine generates changes in gene expression that are essentially opposite to the changes that occur in muscle cells when people are affected by muscle atrophy.

“Green tomatoes are safe to eat in moderation. But we don’t know how many green tomatoes a person would need to eat to get a dose of tomatidine similar to what we gave the mice,” study chief Dr. Christopher Adams said in a statement “We also don’t know if such a dose of tomatidine will be safe for people, or if it will have the same effect in people as it does in mice. We are working hard to answer these questions, hoping to find relatively simple ways that people can maintain muscle mass and function, or if necessary, regain it.”

The end goal is “science-based supplements,” or even simply incorporating tomatidine “into everyday foods to make them healthier.”

Muscle atrophy, or muscle-wasting, is a significant health issue. It can be caused by aging, injury, cancer or heart failure and makes people weak and fatigued, prohibits physical activity and predisposes them to falls and fractures. It affects more than 50 million Americans annually, including 30 million elderly.

Exercise can help but it’s not enough and is not an option for those who are ill or injured, Adams said.

The findings were published April 9 in the Journal of Biological Chemistry.

http://www.laweekly.com/squidink/2014/04/15/green-tomatoes-may-build-bigger-muscles

heart infection

University of Iowa researchers have discovered what causes the lethal effects of staphylococcal infective endocarditis – a serious bacterial infection of heart valves that kills approximately 20,000 Americans each year. According to the UI study, the culprits are superantigens — toxins produced in large quantities by Staphylococcus aureus bacteria — which disrupt the immune system, turning it from friend to foe.

“The function of a superantigen is to ‘mess’ with the immune system,” says Patrick Schlievert, PhD, UI professor and chair of microbiology at the UI Carver College of Medicine. “Our study shows that in endocarditis, a superantigen is over-activating the immune system, and the excessive immune response is actually contributing very significantly to the destructive aspects of the disease, including capillary leakage, low blood pressure, shock, fever, destruction of the heart valves, and strokes that may occur in half of patients.”

Other superantigens include toxic shock syndrome toxin-1, which Schlievert identified in 1981 as the cause of toxic shock syndrome.

Staph bacteria is the most significant cause of serious infectious diseases in the United States, according to the Centers for Disease Control and Prevention (CDC), and infective endocarditis is the most serious complication of staph bloodstream infection. This dangerous condition affects approximately 40,000 people annually and has a death rate of about 50 percent. Among patients who survive the infection, approximately half will have a stroke due to the damage from the aggressive infection of the heart valves.

Despite the serious nature of this disease, little progress has been made over the past several decades in treating the deadly condition.

The new study, led Schlievert, and published Aug. 20 in the online open-access journal mBio, suggests that blocking the action of superantigens might provide a new approach for treating infective endocarditis.

“We have high affinity molecules that neutralize superantigens and we have previously shown in experimental animals that we can actually prevent strokes associated with endocarditis in animal models. Likewise, we have shown that we can vaccinate against the superantigens and prevent serious disease in animals,” Schlievert says.

“The idea is that either therapeutics or vaccination might be a strategy to block the harmful effects of the superantigens, which gives us the chance to do something about the most serious complications of staph infections.”

The UI scientists used a strain of methicillin resistant staph aureus (MRSA), which is a common cause of endocarditis in humans, in the study. They also tested versions of the bacteria that are unable to produce superantigens. By comparing the outcomes in the animal model of infection with these various bacteria, the team proved that the lethal effects of endocarditis and sepsis are caused by the large quantities of the superantigen staphylococcal enterotoxin C (SEC) produced by the staph bacteria.

The study found that SEC contributes to disease both through disruption of the immune system, causing excessive immune response to the infection and low blood pressure, and direct toxicity to the cells lining the heart.

Low blood flow at the infection site appears to be one of the consequences of the superantigen’s action. Increasing blood pressure by replacing fluids reduced the formation of so-called vegetations – plaque-like meshwork made up of cellular factors from the body and bacterial cells — on the heart valves and significantly protected the infected animals from endocarditis. The researchers speculate that increased blood flow may act to wash away the superantigen molecules or to prevent the bacteria from settling and accumulating on the heart valves.

In addition to Schlievert, the research team included Wilmara Salgado-Pabon, PhD, the first author on the study, Laura Breshears, Adam Spaulding, Joseph Merriman, Christopher Stach, Alexander Horswill, and Marnie Peterson.

The research was funded in part by grants from the National Institutes of Health (AI74283, AI57153, AI83211, and AI73366).

http://www.infectioncontroltoday.com/news/2013/08/bacterial-toxins-cause-deadly-heart-disease.aspx

panic-attack

By JAMES GORMAN
Published: February 3, 2013
New York Times

In the past few years, scientists have learned a lot about fear from a woman who could not experience it. A rare illness had damaged a part of her brain known as the amygdala and left her eerily unafraid.

Both in experiments and in life, the woman, known as SM, showed no fear of scary movies, snakes, spiders or very real domestic assaults, death threats, and robberies at knife- and gunpoint.

Although she lived in an area “replete with crime, drugs and danger,” according to an earlier study, because she lacked a functioning amygdala, an evolutionarily ancient part of the brain long known to process fear, nothing scared her.

But recently SM had a panic attack. And the simple fact that she was able to feel afraid without a working amygdala, experts say, illuminates some of the brain’s most fundamental processes and may have practical value in the study of panic attacks.

SM’s moments of fear occurred during an experiment that involved inhaling carbon dioxide through a mask in amounts that are not harmful but create a momentary feeling of suffocation. Not only SM, but two other women, identified as AM and BG, identical twins with amygdala damage similar to SM’s, showed all the physical symptoms of panic, and reported that, to their surprise, they felt intense fear.

The researchers, who report on the experiment in the current issue of Nature Neuroscience, had hypothesized that SM would not panic. John A. Wemmie, a neuroscientist at the University of Iowa and the senior author of the paper, said, “We saw the exact opposite.”

Antonio Damasio, of the University of Southern California, who had worked with SM and some of the researchers involved in this study on previous papers but did not participate in this research, said he was delighted with the results. It confirmed his own thinking, he said, that while the amygdala was central to fear generated by external threats, there was a different brain path that produced the feeling of fear generated by internal bodily experiences like a heart attack. This idea was put forth in a 2011 paper about SM on which he was a co-author.

“I think it’s a very interesting and important result,” he said.

Dr. Joseph E. LeDoux, of New York University, who has extensively studied the amygdala but was not involved in the research, said in an e-mail, “This is a novel and important paper” in an area where there is much left to learn. He said scientists still did not understand “how the brain creates a conscious experience of fear,” whether the amygdala or other systems are involved.

SM scores in the normal range on I.Q. and other tests, and she voluntarily participated in this and earlier studies, all of which showed her lacking in any sort of fear response until now. In one, for example, she walked through a Halloween haunted house and never gasped, recoiled or screamed, as others did, when a person in a costume leapt out of the dark. She also did not seem to learn fear from life experiences.

So what was so unusual about carbon dioxide?

The answer seems to lie in the way the brain monitors disturbances in the world outside the body — snakes and robbers — compared with the way it monitors trouble inside the body — hunger, heart attacks, the feeling of not being able to breathe. External threats clearly are processed by the amygdala. But she had never been tested for internal signals of trouble.

In the experiment that SM and others participated in, they took one deep breath with plenty of oxygen but much more carbon dioxide than air usually contains. Humans are actually not sensitive to how much oxygen they are breathing, but they are sensitive to how much carbon dioxide is accumulating in the body, since it builds up quickly when a person cannot breathe. The sensation is familiar to people who have tried to hold their breath.

The researchers suggest that excess carbon dioxide produces signals that may be picked up in the brainstem and elsewhere, activating a fear-generating system in the brain that a venomous snake or a mugger with a gun would not set off.

One puzzling aspect of the results is that SM and the two other women all reacted so strongly. Among people with normal brains, only those with panic disorder are reliably terrified in carbon dioxide experiments. Most people are not so susceptible, said Colin Buzza, a co-author of the study and a medical student at the University of Iowa Carver College of Medicine, suggesting that perhaps the amygdala is not functioning properly in people with panic disorder.

http://www.nytimes.com/2013/02/04/health/study-discovers-internal-trigger-for-the-previously-fearless.html?_r=0

hippneuron-640x447

As a teenager growing up in New Mexico, Zach Weinberg had the same thing for breakfast every day of high school. Next to his tortilla and cream cheese, which he insists is delicious, was a small, round, yellow pill – an antidepressant called Lexapro. By his senior year, the only thing different was the color of his pill, now a shiny white. This one was Wellbutrin. He’d traded one antidepressant for another. If the pills work, they certainly don’t work for long. Now, at age 23, he’s frustrated at still having to play around with different drug combinations and doses.

The odds are that you know someone in the same situation. According to the National Institutes of Health, approximately one in 10 men and one in four women in the U.S. will suffer from depression at some point in their lives. Clinical depression can come at any time, lasting anywhere from months to years, and is characterized by low self-esteem and a loss of interest in things that were once enjoyable.

Along with various forms of therapy, antidepressant drugs are the most effective treatment. But even when they work, they come with side effects – such as weight gain and trouble sleeping – that can make the symptoms of depression worse. So for people like Weinberg, choosing between one kind of antidepressant and another isn’t really much of a choice.

But that may be changing. New insights into how traditional antidepressants – including the wildly popular SSRIs, or selective serotonin reuptake inhibitor, drugs like Prozac, Paxil and Lexapro – work inside the brain are stimulating the development of a new generation of medications that may work faster and more effectively.

Contrary to what their developers originally thought, many antidepressants have a surprising, indirect way of altering brain chemistry: by stimulating the growth of new neurons and protecting those neurons from dying. “The SSRI hypothesis is really falling apart,” says Paul Currie, a neuroscientist at Reed College in Portland, Ore. He explains that these new ideas have researchers trying something a little different to treat depression.

SSRIs work by manipulating serotonin, one of the most important chemical messengers in the brain. Serotonin is at least partly responsible for everything from eating disorders to the pretty colors and patterns people see while on psychedelic drugs.

When serotonin is released from one neuron and picked up by another in the course of transmitting a message between them, some is taken back up into the original neuron. By blocking this mechanism, SSRIs force more serotonin to circulate in the system, supposedly reducing feelings of depression.

Similar drugs use the same reuptake-blocking technique with other neurotransmitters, usually dopamine and norepinephrine. The success of drugs that target this system provides the basis of the monoamine hypothesis of depression – the idea that depression is a result of a chemical imbalance. That’s why decades of research have been aimed at balancing out our monoamine neurotransmitters, including serotonin.

But it takes a week or two for antidepressants to have any noticeable effect, suggesting that it’s not that immediate boost in serotonin that’s making people feel better. Recently, studies have suggested a different explanation: using antidepressants seems to correlate with having more new neurons in the hippocampus, an area of the brain responsible for many memory processes. Those suffering from depression tend to lose neurons in their hippocampi, so researchers have started to think that the effectiveness of monoamine drugs actually comes from their repairing of damaged brain areas.

Rene Hen is one of those curious researchers. A neuroscientist at Columbia University, Hen used radiation to block neurogenesis – the process of growing, repairing, and protecting new neurons – in mice. Later, when given antidepressants, these mice still showed signs of anxiety and depression, unlike the mice that were generating new neurons. This suggested that neurogenesis is actually essential for antidepressants to have any effect. Instead of waiting for the slower, indirect effect on neurogenesis patients get from SSRIs, researchers are now experimenting with drugs that take more direct routes to stimulate neuron growth.

“If you don’t have to do it through the back door, then absolutely that’s the way to go,” says Reed’s Currie. The aim now is to nail down the indirect effect that Hen identified and make it as direct as possible.

And the first drugs specifically targeting neurogenesis for all sorts of disorders, including depression, are starting to appear. In 2010, Andrew Pieper, a psychiatrist at the University of Iowa, ran a massive screening test on 1,000 small molecules. He discovered eight that had positive effects on neurogenesis in the hippocampus. He picked one, called P7C3, and ran with it. When given to mice that lacked a gene necessary for neurogenesis, P7C3 helped them create new neurons and keep them alive.

“There’s a huge unmet need for treatments that block cell death,” Pieper says. And the hope is that treatments for depression derived from P7C3 will work faster, better, and with fewer side effects than SSRIs. Although Peiper and his team have only tested P7C3 on mice, he’s optimistic about its effects in humans and is on the hunt for a commercial partner to develop it.

Neuralstem Inc., a Maryland-based pharmaceutical company, has just announced that their first round of human clinical testing on a similar drug was successful. Their drug, NSI-189, targets neurogenesis in the hippocampus by actually creating new neurons and has been successful in animal models, but these are the first tests in humans.

Despite the early success of these treatments, other scientists are concerned that a drug targeting neurogenesis might be meddling with that system prematurely. “I’m a little worried that, again, we have an oversimplified model,” Currie says. It’s like stirring up a bowl of soup, he continues, “without any thought as to what makes it taste good.”

Brian Luikart at Dartmouth College’s Geisel School of Medicine agrees. “One possibility,” he says, “is that there are global changes in the brain that enhance neurogenesis in the hippocampus.” If that’s true, then more neurogenesis could just be one of many effects of SSRIs without being the key to their success. Although the links between neurogenesis and antidepressants are well established, there is still no evidence to suggest that solely enhancing neurogenesis can help fight depression in humans. “Increasing neurogenesis does not increase happiness,” he says.

Luikart also worries that, while a neurogenesis drug may have fewer side effects, the ones it does have could be even more damaging – especially for cancer patients. A drug that keeps neurons alive could potentially do the same to tumor cells.

But Pieper says he hasn’t seen any negative effects. Neuralstem also says there haven’t been any health concerns in their trials. And even if there are side effects like those Luikart is worried about, it might be worth the risk for those with severe depression.

Neurogenesis drugs are still years from being commercially available, however. Pieper’s is still in pre-clinical testing, and Neuralstem’s, while farther along, is still years away from patients. Until then, Zach Weinberg and the rest of us are just going to have to stick with our reuptake inhibitors and cream cheese tortillas.

http://scienceline.org/2013/01/shiny-happy-neurons/