Back in the 1980s, gene therapy was one of science’s greatest hopes and hypes, and researchers predicted the technique would be used to cure a huge range of illnesses. During the 90s, many early gene therapy trials were effective or downright dangerous, some causing cancer or even death. But more recently, scientists who stuck with gene therapy have started to see positive results, with promising treatments for malformed hemoglobin, color blindness, and depression. (See the DISCOVER magazine feature “The Second Coming of Gene Therapy” for more.) Now, researchers have announced that they’ve successfully treated the symptoms of Parkinson’s disease in a small group of people—a far cry from a cure, but still a step in the right direction.

I Once Was Blind but Now I See

The theory behind gene therapy is simple: A healthy gene hitches a ride into the patient’s genome on a virus, replacing the genes responsible for some genetic disease or disorder. Actually doing this is more difficult, because humans have a little thing called an immune system that’s remarkably efficient at finding and destroying foreign bodies. After the first U.S. death from gene therapy in 1999, and leukemia cases in France the same year, many started to think that gene therapy was more of a problem than an answer.

The early and awful failures forced all of the researchers in the field to retreat and reconsider the staggering complexity that challenged them. They could not just replace a bad gene with a good gene, as some early pundits had hoped—they also had to orchestrate the nuanced and elaborate dance between the gene products (proteins) and the patient’s immune system, which could recognize a foreign body and viciously attack it. After that was settled, gene therapists still had to find a suitable virus, or vector, to carry replacement genes into human cells without inciting a damaging or deadly immune response…. It was this new perspective more than anything else that turned gene therapy from a simple but failed and frustrated hope into, once again, medicine’s next big thing—a stunning spectacle of hubris, ignominy, and redemption on the scientific stage. [DISCOVER]

New: Gene Therapy and Parkinson’s Disease

While there’s no cure for Parkinson’s as of yet, doctors have an arsenal of methods, ranging from drugs, brain stimulation, and (now) gene therapy that help reduce the disease’s symptoms. Hopes for using gene therapy to alleviate Parkinson’s effects aren’t new. What is new is that scientists have successfully completed the first randomized, controlled, double-blind trial of treating Parkison’s patients with gene therapy—and they found that it significantly improved debilitating symptoms such as tremors, motor skill problems, and rigidity. (more…)

In a society where pill-popping is the answer to many a medical malady, severely dysfunctional or damaged organs are especially frustrating—they’re usually beyond the reach of any known drugs. Cell-based therapy, though, is no drug: Using patients’ own cells, medical experts have successfully grafted the first engineered-from-scratch urethras.

The story starts with five Mexican boys, aged 10 to 14, whose urethras were damaged beyond repair because of accidents.

“When they first came in, they had a leg bag that drains urine, and they have to carry this bag everywhere they go,” says Dr. Anthony Atala of Wake Forest University in North Carolina. “It’s uncomfortable and painful. So these children were mostly sitting or bed-bound.” [NPR]

Currently the usual treatment calls for an artificial graft, which has a failure chance as high as 50% (and failure here means a lifetime of infections and incontinence). “When an organ or tissue is irreparably damaged or traumatically destroyed, no amount of drugs or mechanical devices will restore the patient back to normal,” regenerative medicine expert Chris Mason, from University College London, told the BBC. (more…)

From the perspective of a kidney cell, light is a toxic substance: It spends its life hidden under layers of skin and guts, far away from any kind of intense illumination. As a result, biologists using microscopes to study kidney cells and other living cells are always racing the clock—the very light required to see the cell will also kill it. But light toxicity is no longer an issue with the invention of a new microscope that uses focused sheets of light to create 3-D movies of living cells.

The technique is called Bessel beam plane illumination microscopy, and it works by shooting thin planes of light toward the side of a cell, illuminating the specific plane the microscope is focusing on, instead of drowning the entire cell in top-down light.

“We have for the first time a technology that allows you to look at the three-dimensional complexity of what’s going on, at the sort of rates at which things happen within cells,” Dr [Eric] Betzig [the Howard Hughes Medical Institute (HHMI) physicist who led the research] said. [BBC]

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Earlier this week at a scientific conference in Boston, HIV researchers announced a remarkable success in countering the virus’ drain on the immune system. But this early step is far from a cure.

Why it’s exciting:

Carl June and colleagues tested six male patients who already had HIV and were taking a standard antiviral regimen. Like many HIV patients, the drugs helped them, but their counts of immune cells stayed low. June’s team tested a therapy created by Sangamo BioSciences in Richmond, California, that alters a patient’s actual white blood cells to make them more HIV-resistant.

Researchers removed a sample of CD4⁺ T cells, the type of immune cells affected by HIV, from each man and used Sangamo’s enzyme to disrupt the CCR5 gene, which encodes a protein that HIV uses to enter CD4⁺ cells. The engineered cells were then infused back into the patients. Immune-cell counts subsequently rose for five of the six patients who received the therapy. “It’s very exciting,” says John Rossi, a molecular biologist at the City of Hope’s Beckman Research Institute in Duarte, California. “If they did this several times in a given patient, you could establish a high percentage of resistant cells.” [Nature]

The idea came from the “Berlin Patient,” who we’ve written about before at 80beats. He became famous after receiving a donation of bone marrow from someone who carried a mutation in CCR5 that made them resistant to HIV.

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Swine flu is not gone, and it is not stagnant. Though the public health scare about the 2009 swine flu pandemic subsided, the virus—like avian flu—remains in pockets of animals, shuffling its genes while hidden from the watchful eyes of virus experts. Virologists call this genetic switcheroo “reassortment,” and it’s how new and dangerous strains of flu snuck up on humankind in the past—and how they could do it again. This time, though, virologist Jinhua Liu and colleagues are trying to get a jump on the viruses.

For a new study in the Proceedings of the National Academy of Sciences today, this team of Chinese researchers simulated what could be a dire situation for humans: swine flu (H1N1) and avian flu (H9N2) together in one animal. When these flu strains are together they can exchange genetic material. So to test what that mixing might produce, Liu’s team swapped genes between the two and created 127 hybrid viruses, testing each on mice.

Eight of these hybrid strains turned out to be more virulent and dangerous in the mice than their parent strains of swine flu and bird flu. [National Geographic]

According to Dutch virologist Ab Osterhaus, we can’t be sure that these eight nasty strains are the ones that would hit humans hardest—animal studies aren’t perfect.

“Mice mirror, to a certain extent, what happens in humans,” he says, but they are not perfect model animals. Liu agrees. He plans to investigate how contagious his new viral blends are in guinea pigs and ferrets—animals whose respiratory system better reflects our own feverish battle with flu. [ScienceNOW]

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A study of an experimental drug from the company Vertex, called VX-770, successfully reduced lung problems in CF patients, and the company hopes to try for approval of the drug later this year. If all goes well, doctors may soon have their first drug to treat the cause of this devastating disease, instead of just combatting the symptoms.

Cystic fibrosis is a genetic disease that impairs lung and digestive function. In particular, the normally thin layer of mucus in the lungs thickens up and impairs breathing; this happens because patients have a faulty version of a protein that helps clear mucus.

About 1800 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been implicated in the disease. The gene encodes a molecular channel that shuttles chloride ions across cellular membranes, and people with two mutated copies develop mucus-filled lungs susceptible to infection. Few patients live to see their 30s. In 1989, CF became the first disease pinned to a specific gene mutation, without the benefit of knowing the protein first. [Nature]

This newest test was a Phase III trail of Vertex’s drug, which was funded in part by the Cystic Fibrosis Foundation. The treatment goes after one major genetic mutations that causes the disease, called G551.

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Even with 15 percent of their hearts removed, newborn mice possess the extraordinary ability to mend themselves, researchers report today in the journal Science. It’s the first time that mammals outside of the womb have shown the regenerative ability to repair the heart.

Only newborn mice could regenerate part of their hearts, and they lost this ability after about a week after birth. Still, the results were quite impressive: Olson’s team removed 15 percent of the heart one day after birth, and when the researchers checked up three weeks later, the whole heart was repaired in 99 percent of the mice. Until now, scientists had seen fish and amphibians regenerate heart tissue as adults, but only embryonic mammals had been spotted doing the same.

“When a person has a heart attack and heart muscle cells are lost, the heart loses pump function, causing heart failure and eventual death,” said Eric Olson, a molecular biologist at Southwestern Medical Centre in Dallas, Texas. “Now that we know that the mammalian heart indeed possesses the potential to regenerate, at least early in life, we can begin to search for drugs or genes or other things that might reawaken this potential in the adult heart of mice and eventually of humans.” [The Guardian]

First they have to understand what the newborn rodent’s bodies are up to. Initially, Olson and colleagues weren’t sure how the mice were mending themselves—with stem cells, or cells that had already become muscle cells. But the appearance of the cells gave them away, says Dr. Stephen Badylak, who wasn’t involved in the study.

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If a vaccine injures a child, should the parents be allowed to sue in state court? That’s a question lawyers, vaccine makers, parents, and Congress have wrestled over for a quarter century. This week, the United States Supreme Court brought forth a ruling that keeps the status quo: No, you can’t.

The justices, voting 6-2, said a 1986 federal law preempts claims that a drugmaker should have sold a safer formulation of a vaccine. The law, designed to encourage vaccine production by limiting patient suits, channels most complaints into a company- financed no-fault system that offers limited but guaranteed payments for injuries shown to be caused by a product. [Bloomberg]

The case in question, which has been kicking around for nearly two decades, was brought by Russell and Robalee Bruesewitz on behalf of their daughter, Hannah. In 1992 she began experiencing seizures after receiving a diphtheria, pertussis and tetanus shot made by  Wyeth [part of Pfizer]. At the time, her parents tried to file a claim with that government-created system.

When a special Vaccine Court within the Court of Federal Claims ruled that her injuries couldn’t be linked with the vaccine, her parents tried to move the case to Pennsylvania state court. The Third Circuit Court of Appeals eventually ruled that the claim was pre-empted by federal law, a decision upheld by the Supreme Court. [Wall Street Journal]

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A bilingual brain is a healthy brain. (Un cerebro bilingüe es un cerebro sano.)

Speakers of two languages may have extra defenses against the onset of dementia and Alzheimer’s disease—that’s according to new research announced this weekend at the American Association for the Advancement of Science meeting in Washington, DC. Psychologist Ellen Bialystok and her team studied more than 200 Alzheimer’s patients with about the same level of mental acumen, about half of whom were bilingual and half of whom were monolingual. The result: On average, the speakers of multiple languages had been diagnosed four years later in their lives. Says Bialystok:

“Being bilingual has certain cognitive benefits and boosts the performance of the brain, especially one of the most important areas known as the executive control system. We know that this system deteriorates with age but we have found that at every stage of life it functions better in bilinguals. They perform at a higher level. It won’t stop them getting Alzheimer’s disease, but they can cope with the disease for longer.” [The Guardian]

To get a look at that system, the team took CT scans of the patients’ brain. That’s when they found something curious: The physical ravages of Alzheimer’s were actually more advanced in the brains of bilinguals, despite the fact that they were mentally more protected.

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They’re about three and a half feet tall and their origins are mysterious, but an isolated group of Ecuadorians with a genetic mutation causing dwarfism are making news for another reason: They hardly ever get cancer or diabetes. Medical researchers say the villagers’ genetic protection from these diseases could lead to preventative treatments for the general population–and could therefore increase human longevity.

The villagers’ condition is called Laron syndrome, which is caused by an insensitivity to growth hormone.

Laron syndrome results from a mutation in the gene that codes for growth hormone receptor (GHR), a protein that binds with the human growth hormone and ultimately results in the production of the insulin-like growth factor 1 (IGF1), causing cells to grow and divide. When a person has two of these mutated and non-working genes, they can develop the disease. [LiveScience]

Jaime Guevara-Aguirre, the leader of the study about the Ecuadorians appearing in Science Translational Medicine, has been looking into their condition and extraordinary resistance to age-related diseases for more than two decades, since his serendipitous discovery of the people while riding horseback in Ecuador.

“I discovered the population in 1987,” Dr. Guevara-Aguirre said in an interview from Ecuador. “In 1994, I noticed these patients were not having cancer, compared with their relatives. People told me they are too few people to make any assumption. People said, ‘You have to wait 10 years,’ so I waited. No one believed me until I got to Valter Longo in 2005.” [The New York Times]

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It was a stroke of serendipity that may one day help those who hide under comb overs or wear wigs: scientists studying how mice bowels react to a stress-reducing chemical have inadvertently discovered a cure to baldness. But unfortunately, it looks like this cure won’t apply to genetic baldness, which is by far the main cause of most hairless pates. Still, researchers hope the lucky find will eventually be used to battle at least some of the bare heads of humans.

The story begins with mice that were genetically modified to produce too much corticotrophin-releasing factor, or CRF–a type of stress hormone. Normally, as these stressed-out rodents age, their backs lose hair. But a group of researchers from the Veterans Administration and the University of California at Los Angeles didn’t care about hair, they just wanted to study the effects of a chemical on the modified mice.

Researchers at the Salk Institute developed a peptide called “astressin-B”, which blocks the action of CRF, and the teams injected the peptide into the bald mice. They weren’t thinking about baldness at all — they wanted to test whether the astressin had any impact on the mice’s gastrointestinal tracts. The first injection did nothing, so the team gave the mice additional injections over five days, and then measured the effects on the newly de-stressed mice’s colons. [Popular Science]

With most of the experiment done, the researchers forgot about the mice for three months. Then they returned for some follow-up tests:

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Villagers living in Ecuador’s remote rainforests won a victory in one of the longest-running, most complex environmental lawsuits ever this week. A judge in Ecuador awarded $8.6 billion—with the possibility of another $10 billion or so on top of that—to plaintiffs suing Chevron for polluting the Amazon region during decades of energy exploration. But in a turn of events befitting the tangled web of international environmental law and fights over who should pay for pollution, there’s no guarantee the plaintiffs will actually see that money.

Judge Nicolas Zambrano awarded the $8.6 billion to pay for cleanup and for health care for Ecuadorians made sick by the pollution, plus 10 percent of that total added on top as reparations to the Amazon Defense Coalition. If Chevron doesn’t publicly apologize within 15 days of the ruling—and it isn’t going to—the ruling tacks on another $8.6 billion in punitive damages.

The pollution case itself is full of weird twists and turns. The first thing to know about this mess is that “Chevron” didn’t pollute the region—at least, not under that name.

Chevron does not, in fact, operate in Ecuador today; the American company acquired the lawsuit when it bought Texaco in 2001. Texaco started oil exploration activities with Ecuador’s state oil company Petroecuador back in 1964, and for the next three decades, the 47 plaintiffs say, the company contributed to dumping billions of gallons of waste oil in the region, causing loss of livelihood, widespread health problems and up to 1400 deaths. [TIME]

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Sometimes, even a tiny cut can have serious and unexpected consequences. New research reveals that even a minor flesh wound can cause previously dormant cancer cells to develop into tumors.

The study, published in the Proceedings of the National Academy of Sciences,  focuses on basal cell carcinoma, a variety of skin cancer associated with hair follicle cells. Basal cell carcinoma is the most common type of skin cancer, and while it rarely metastasizes or kills it’s still considered malignant.

Biochemists Sunny Wong and Jeremy Reiter, from the  University of California, San Francisco, wanted to see how tumors develop from cancerous mutations. To do that, they genetically modified mice so that their hair follicle stem cells expressed the human basal cell carcinoma gene. After giving some of the mice a small cut, and leaving others alone, they discovered that tumors only formed on the hurt mice.

When skin is cut, hair-follicle stem cells migrate to the injury. Wong says pre-cancerous cells can lie dormant in the body until a trigger, such as radiation or a build up of mutations, pushes them into forming a tumour. “In this case, wounding got cancerous cells out of their resting phase,” he says. [New Scientist]

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The bacterium called Neisseria gonorrhoeae is what gives humans the sexually transmitted infection gonorrhea. And it also takes something: human DNA. Northwestern University researchers report in the journal mBio that they’ve found pieces of human DNA in samples of the bacteria.

Gonorrhea is one of very few diseases exclusive to our species, and is one of the oldest recorded diseases in human history. An ancient disease that resembles gonorrhea’s symptoms is even described in the Bible, according to Hank Seifert, senior author of a paper on the gene transfer. [Popular Science]

Seifert and colleague Mark Anderson looked at 14 different samples of N. gonorrhoeae. Three of them possessed the chunk of human DNA. And they only saw it in the gonorrhea bacteria:

The pair looked for the same human DNA fragment in the genetically related bacterium Neisseria menigitidis, known to cause meningitis. “We screened many isolates and it wasn’t present,” says Seifert. That means the transfer to N. gonorrhoeae must have occurred since the two bacterial species diverged around 200,000 years ago. [New Scientist]

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As more hospitals have begun using DNA testing to analyze babies with birth defects, doctors have occasionally discovered that a family’s little bundle of joy is also a product of incest. Since this is a new dilemma brought on by the spread of technology, doctors are now debating how to handle these incest surprises.

Geneticist Arthur Beaudet at Baylor College of Medicine addressed the issue yesterday in an article in the medical journal The Lancet. The genetic test, the single nucleotide polymorphism-based array, helps doctors identify missing genes (and can therefore help explain a child’s birth defect or disability)–but it also identifies swaths of identical DNA that a child may have inherited from two closely related parents.

In the few months that Baylor has been performing these detailed genetic tests, there have been fewer than 10 cases of consanguinity — the phenomenon of inheriting the same gene variations from two closely related people, said Dr. Arthur L. Beaudet, chairman of Baylor’s department of molecular and human genetics. However, wider use of such testing in children with disabilities is expected to identify additional cases of incestuous parentage. [ABC News]

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