Reversing Age Related Memory Loss

Researchers estimate that roughly 20 to 30 percent of people age 75 and older have elevated glucocorticoid levels (more precise figures aren't available). Most affected is so-called declarative memory, the ability to learn new facts and remember, for example, lists. People who suffer age-related memory loss are at higher risk for developing Alzheimer's and other forms of dementia, though the condition is not itself considered a form of dementia. _TechnologyReview

A research team at the University of Edinburgh have developed a new compound that appears to prevent and reverse age-related memory decline in mice. Their approach utilises a "gene knockout" approach against an amplifier of glucocorticoid effect present in brain cells.

"What's most surprising is that even short-term inhibition was able to reverse memory loss in old mice," says Jonathan Seckl, a professor of molecular medicine who was involved in the research. "I don't think people had realized this was so reversible. It takes [the animals] back to being relatively young."

The researchers hope to develop equivalent human therapies and are now more extensively studying the safety of a closely related compound in animals. They aim to begin human testing within a year.

Scientists have long known that glucocorticoids--a class of steroid hormones that mediate our response to stressful situations--play a role in age-related memory decline. Although short-term exposure to glucocorticoids enhances the formation of memories during stressful situations, chronically high levels of the hormones are linked to greater memory loss with age, both in humans and animals. The exact mechanism underlying this link is unclear, but researchers theorize that excess exposure to the hormones makes parts of the brain more vulnerable to damage.

Seckl and his collaborators focused on an enzyme called 11β-hydroxysteroid dehydrogenase type 1 (11 β-HSD1). This enzyme generates an active version of the key glucocorticoid hormone within brain cells and some other tissues, providing a target for fine-tuning the system without blocking the overall stress response. Tinkering with the enzyme seems to have little effect on blood levels of glucocorticoids, which are produced in the adrenal glands. Instead, "this enzyme acts as an intracellular amplifier of glucocorticoids," says Seckl. "If you take out the amplifier, you still have stress hormones, but they shout less loudly and cause less wear and tear."

The Edinburgh team showed that knocking out either one or both copies of the gene for this enzyme in mice preserved the animals' memory into old age. To determine whether blocking the enzyme could improve memory in already aged animals, researchers then developed a compound designed to cross into the brain and inhibit the enzyme. Just 10 days of treatment in two-year-old mice--the maximum lifespan for a typical lab mouse--was enough to improve the animals' performance on a test of spatial memory. The treatment "returned mice to the equivalent of when they were young and fully functioning," says Brian Walker, another researcher involved in the study. "It's important to emphasize that we are trying to target the pathology--the role that glucocorticoids play in age-related memory decline--not just globally improving memory." The research was published last week in the Journal of Neuroscience. _TechnologyReview

Brian Wang looks at another approach to augmenting human brainpower

Also published at Al Fin

Open Source Biotechnology: The Wonder and the Terror

As recently as a decade ago, the tools and techniques for such fiddling were confined to a handful of laboratories like those at leading research universities. Today, do-it-yourself biology clubs have sprung up where part-timers share tips on how to build high-speed centrifuges, isolate genetic material, and the like. The movement has been aided by gear that can turn a backyard shed into a microbiology lab. _WSJ

With the emergence of open-source biohacking, a number of scientists and authorities are starting to worry about the possibility that a biohacker will create some type of super-microbe which could cause a significant disease outbreak. Here you can find a zipped download introduction to biohacking.

The new fear, though, is that scientific advances that enable amateur scientists to carry out once-exotic experiments, such as DNA cloning, could be put to criminal use. Many well-known figures are sounding the alarm over the revolution in biological science, which amounts to a proliferation of know-how—if not the actual pathogens.

"Certain areas of biotechnology are getting more accessible to people with malign intent," said Jonathan Tucker, an expert on biological and chemical weapons at the James Martin Center for Nonproliferation Studies.

Geneticist Craig Venter said last month at the first meeting of a presidential commission on bioethics, "If students can order any [genetic sequences] online, somebody could try to make the Ebola virus."

Mr. Venter is a pioneer in the field whose creation of a synthetic organism this spring helped push the debate about the risks and rewards of bioscience from scientific journals to the corridors of power in Washington. "We are limited more by our imagination now than any technological limitations," Mr. Venter said.

Scientists have the ability to manipulate genetic material more quickly and more cheaply all the time. Just as "Moore's Law" describes the accelerating pace of advances in computer science, advances in biology are becoming more potent and accessible every year, experts note. _WSJ

Of all the things likely to escape from garage biohacking outposts, none are likely to bring about the end of the human species. Some of them may even be beneficial for health and long life.

Just as some of the fastest developments in personal computing emerged from basements and garages, so is it possible for home-based biohackers to make important contributions to bioscience and biomedicine. Curiosity drives most small scale hacking of all kinds -- the desire to understand how things work.

For humans who are interested in going beyond the ordinary in terms of lifespan, intelligence, sleep requirements, strength, speed, etc. the answers may well arise from small scale independent labs -- given how over-regulated and over-restricted all aspects of government sanctioned biomedicine are becoming in western countries.

Is there a danger? Yes, there is always a danger, and all of us should stay alert for persons who seem to be several cards short of a full deck. But that shouldn't stop us from pushing the limits.

Regenerative Medicine Advances

The promise of regenerative medicine involves a future where replacement organs and tissues can be re-grown in a lab from a person's own cells, then transplanted into the person as brand-new, fully functioning replacement tissue. Replacement lung tissue, replacement heart tissue, replacement ligaments and tendons, replacement skin, kidneys, muscle, intestine, bladders, and on and on. But first, scientists have to find a good way to grow millions and billions of healthy stem cells from a person's own cells, and keep them alive long enough to turn them into the proper tissue, and grow them on a proper scaffold into the proper replacement organs.

Investigators from the Massachusetts Institute of Technology (MIT) recently developed a new type of support structure for stem cells, which allows them to remain alive for weeks without using any foreign genetic material.

Generally, substrates for growing stem cells contain animal cells or tissue, but these can easily contaminate the samples themselves, which means that they can lose some of their capabilities.

This is an especially serious consequence for induced pluripotent stem cells, which are biological units that can transform into any type of tissue in the human body.

Only environmental conditions dictate whether they will turn into nerve cells, or into pancreatic tissue.

Due to this amazing differentiation ability they have, these cells hold great promise for treating a number of disorders, such as for example Parkinson's, multiple sclerosis and spinal cord injuries.

But, in order to make the best of them, researchers need to be able to grow them in sufficiently large quantities, and this is proving to be extremely difficult due to the lack of proper substrates.

One of the main issues in this field of research is the fact that human stem cells are now grown with the aid of cells or proteins derived from mice embryos. If these foreign chemicals would interact with the human body, they would definitely cause an allergic reaction.

Thanks to the MIT collaborations, which includes biologists, materials engineers and chemists, scientists now have a synthetic surface that features no material from mice or other animals.

The data the team recorded of the new surfaces show that they promote and sustain “all-natural” stem cell growth and reproduction for at least three months. Longer periods are also possible, the group says.

Another impressive feat the MIT experts achieved with their new material is the fact that it allows for researchers to separate colonies of identical cells from each other. The surface allows single cells to form colonies of cells of that type with considerable ease.

Details of the new investigation appear in the August 22 issue of the esteemed scientific publication Nature Materials, e! Science News reports. _Softpedia

Another report from ScienceDaily

“For therapeutics, you need millions and millions of cells. If we can make it easier for the cells to divide and grow, that will really help to get the number of cells you need to do all of the disease studies that people are excited about,' says MIT postdoctoral associate Krishanu Saha, one of the co-first authors of the paper. 

The work was led by MIT professors Robert Langer, Rudolf Jaenisch and Daniel G. Anderson, in collaboration with Saha and postdoctoral researcher Ying Mei. _Softpedia

This report from Brian Wang on Swiss stem cell research, suggests that mature tissue-derived stem cells can be programmed across germ layer boundaries. This finding hints at the possibility of creating virtually any type of cell or tissue from any other type of tissue -- including easily sampled tissues such as skin or blood.

Cross-posted at Al Fin

The Aging Brain: Endangered by Runaway Development?

Mehmet Somel, a Turkish researcher doing post-doctoral work in Shanghai, has uncovered some fascinating genetic evidence suggesting that inappropriate-for-age gene regulation may be endangering aging brains:

Researchers have now identified a gene regulatory link between changes in the young and aging brain.

The brain undergoes rapid growth and development in the early years of life and then degenerates as we progress into old age, yet little is known about the biological processes that distinguish brain development and aging.

Underlying brain development is the complex and coordinated process of gene regulation.

"In development, many genes are turned on and off by regulators, such as transcription factors and microRNAs. The question is, do all of these regulatory processes cease once adulthood is reached, or are they still active in aging?" said Mehmet Somel, postdoctoral researcher at the Shanghai Institutes for Biological Sciences.

The researchers investigated messenger RNA (mRNA), microRNA, and protein expression changes in the prefrontal cortex of humans and rhesus macaque monkeys over the life span of each species.

The group found that distinct patterns of gene regulation in the prefrontal cortex do not stop at maturity, instead persisting into old age, a phenomenon that was observed for many different functional processes.

...The researchers showed that this process begins as early as three to four years of age, suggesting that these changes may be normal developmental regulation that continues long into old age.

While this regulation is likely to be beneficial during development, at old age continuation of the gene regulation, or "runaway" development, might be detrimental.

Interestingly, they found the runaway neuronal development to be conserved in macaques, but it occurs an accelerated rate.

Because the regulatory processes progress much faster, the authors suggest that this could be a significant contributor toward limiting the life span of macaques to only about one-third that of humans. _SiFy

Researchers will now need to determine whether a more "age-appropriate" pattern of gene regulation would allow for persistence of normal brain functioning further into old age.

It is known that DNA repair loses efficiency with increasing age. If inappropriate genes are consistently "over-clocked" at levels more appropriate to younger ages, the compounding of genetic errors due to inefficient DNA repair would occur more quickly and take on more significance.

This is a fascinating area of study, well worth following.

Can Delaying Puberty & Extending Childhood Increase Lifespan?

Puberty seems to be arriving at earlier ages for both boys and girls. There are many reasons why puberty onset is earlier now, but most of these reasons are still unclear. The problems that arise from premature puberty include violence, higher risks of cancer and diabetes, increased behavioural problems (drugs, alcohol, delinquency etc), isolation from peer groups -- even a change in growth rates for the children of girls with premature onset of puberty.

ImageSource

...children who go into early puberty are prematurely sexualised and too immature to deal with the implications. They are more vulnerable to sexual abuse, inappropriate sexual behaviour, sexually transmitted diseases and teenage pregnancy. “It means that children develop sexually much earlier,” Stanhope says. “They are physically ready for sexual reproduction but mentally completely unready.”

Studies have shown that adolescents who go through puberty earlier are involved in more risk-taking behaviour, such as taking drugs, binge drinking and breaking the law. A premature increase in testosterone can lead to aggression in boys who lack the maturity to control impulses. “We all realise that testosterone is a very difficult hormone to learn to live with,” Stanhope says, tapping a pencil vigorously on his pockmarked table, “and if you get a rise in testosterone outside the normal physiological age, then it’s even more of a problem.”

Research published this year in the Australian and New Zealand Journal of Criminology also found increased aggression in girls who reached puberty early. In Britain the uncomfortable reality that children are becoming sexually mature earlier has been overlooked in the recent debate about the over-sexualisation of children. Instead of simply focusing on cynical manufacturers producing padded bras for seven-year-olds, perhaps we should also consider how to respond to the new reality that some girls are now growing breasts at this age.

Stanhope also points out that for women there may be long-term health problems, because early puberty increases exposure to oestrogen. According to Cancer Research UK, a girl who has her first period a year later than her contemporaries has 5% less risk of developing breast cancer in later life. “There may be an important link with breast and ovarian cancer,” Stanhope says. “The earlier a girl has her period, the longer her exposure to oestrogen and this may well have very important sequelae for oestrogen-dependent tumours. This increases her risk of breast cancer, ovarian cancer and of developing cardiovascular problems.”

Girls who reach puberty early are also more likely to develop type 2 diabetes. A 37-year-long study of 61,000 Norwegian women showed that women who got their first period at ten or 11 had a 10% higher mortality rate than those who got their period four years later. _PubertyBlues

Scientists are beginning to home in on the physiological initiators of puberty, and have found a way to delay puberty in mice. By "knocking out" a specific gene, IGF-1R, researchers have both delayed puberty and maintained normal reproductive function after puberty in these knockout mice.

Pubertal onset, initiated by pulsatile gonadotropin-releasing hormone (GnRH), only occurs in a favorable, anabolic hormonal milieu. Anabolic factors that may signal nutritional status to the hypothalamus include the growth factors insulin and IGF-1. It is unclear which hypothalamic neuronal subpopulation these factors affect to ultimately regulate GnRH neuron function in puberty and reproduction. We examined the direct role of the GnRH neuron in growth factor regulation of reproduction using the Cre/lox system. Mice with the IR or IGF-1R deleted specifically in GnRH neurons were generated. Male and female mice with the IR deleted in GnRH neurons displayed normal pubertal timing and fertility, but male and female mice with the IGF-1R deleted in GnRH neurons experienced delayed pubertal development with normal fertility. With IGF-1 administration, puberty was advanced in control females, but not in females with the IGF-1R deleted in GnRH neurons, in control males, or in knockout males. These mice exhibited developmental differences in GnRH neuronal morphology but normal number and distribution of neurons. These studies define the role of IGF-1R signaling in the coordination of somatic development with reproductive maturation and provide insight into the mechanisms regulating pubertal timing in anabolic states. _JCI

Scientists will find additional triggers for pubertal onset besides insulin and IGF-1, and some of those factors may provide a more benign approach to the delaying of puberty.

Paradoxically, IGF-1 is vital for normal development of mice, but knocking out IGF-1 receptors in certain flies and worms can increase lifespan. That paradox is still being studied.

So -- how long should puberty be delayed, if at all? If childhood could be extended for several more years without impairing the ability of the child to learn and mature psychologically, would the potential health and societal benefits be worth the postponement of sexual development of the child?

What if aging itself were to be postponed along with puberty? If total lifespan were extended by the number of extra years a person spent in childhood, would that be beneficial to society or not? What if a person could live an extra 20, 30, or 50 years -- but had to spend those extra years as a pre-pubertal child. Would it be worth it?

Those who see increased longevity as a sure path to overpopulation collapse of Earth's ecosystem, would insist upon some form of sterilisation for those who opt for longevity. In some countries, laws of that type -- mandating permanent sterilisation for anyone undergoing longevity treatments -- should be expected.

Extended pre-puberty is a form of time-limited and (probably) reversible sterilisation, so any longevity approach that also delayed puberty significantly, should not raise the hackles of those suffering from overpopulation anxiety too much. But there are likely to be a large number of objections to such treatments, all the same.

Modern societies appear to see children in a schizoid manner. Fewer children are born, so the one or two children a family does have, are cherished and pampered. On the other hand, children are seen as a hindrance to a hedonic lifestyle, an exorbitant expense and often a great bother. Overall, most children do not seem to be raised or educated very well in modern societies, judging by observable results.

While childhood is not prolonged in modern societies, an incompetent adolescence is certainly prolonged -- in many cases indefinitely. Given the choice between a prolonged childhood leading into an accelerated but prepared-for adolescence, and the current state of lifelong incompetent adolescence commonly seen in the affluent world, most Al Fin mental health professionals would choose the prolonged childhood combined with a prepared-for adolescence that leads into a responsible and competent adulthood.

Previously published at Al Fin

A New Class of Molecules that May Cure Alzheimer's

New nerve cells are constantly born in the hippocampus, but even in the normal adult brain, most of these newborn neurons die before they become functional.

And they fare much worse in the hippocampus of Alzheimer's patients.

Physical activity, an active social life and other intellectually and emotionally enriching experiences promote the birth and maturation of new neurons.

The scientists wanted to find compounds that can protect newborn neurons from dying.

P7C3 was selected from among about 1,000 compounds tested on mice.

The compound was found to help the survival of neurons in adult mice, which were genetically engineered to lack a gene that is crucial for the survival of newborn nerve cells. _IndiaToday

ScienceDaily
University of Texas Southwestern have reported in Cell the discovery of a molecule -- P7C3 -- that has the ability to protect brain cells, and trigger the production of new neurons. The scientists believe that new compounds in the same class as P7C3 may hold the key to slowing or temporarily reversing the progress of Alzheimer's Disease and other neurodegenerative conditions.

In a new study published today in the journal Cell, researchers screened 1000 molecules in mice to see which ones enhanced production of new neurons in a brain area involved in learning and memory. This region, known as the hippocampus, is one of two spots known to birth new neurons in the adult mammalian brain. It takes 2 to 4 weeks for the cells to migrate to the appropriate location and integrate into the existing neural circuitry, and many of them die along the way.

The researchers found that one compound, dubbed P7C3, protected these newborn neurons from dying. When given to mice genetically engineered to have very little new nerve cell growth, the compound seemed to repair the abnormal hippocampus. It could also increase birth and survival of new neurons in older rats, according to a press release from UT Southwestern Medical Center. The animals also had improved memory: they could better remember the location of a platform submerged in water, a standard test of learning and memory in rodents.

...

According to a release from the journal Cell, where the paper was published;

Two other drugs (Dimebon and Serono compounds) - both of which bear structural similarities to P7C3 -also encourage the growth of new neurons. It's tempting to think that all three compounds work in the same way.

In fact, Dimebon first came to the attention of researchers based on anecdotal reports by Russian physicians that the drug may ameliorate the symptoms of age-related cognitive decline. Unfortunately, unpublished reports from a phase 3 clinical trial have since failed to provide evidence that the drug could stave off the memory loss that comes with Alzheimer's disease.

In light of the new findings, it may be worth another look. "The speculative idea that these chemicals share a common mode of action will only be rigorously tested upon identification of their molecular target(s)."

 _TechnologyReview

Pieper, McKnight and colleagues tested more than 1000 small molecules in living mice. One of the compounds, designated P7C3, corrected deficits in the brains of adult mice engineered to lack a gene required for the survival of newborn neurons in the hippocampus. Giving P7C3 to the mice reduced programmed death of newborn cells -- normalizing stunted growth of branch-like neuronal extensions and thickening an abnormally thin layer of cells by 40 percent. Among clues to the mechanism by which P7C3 works, the researchers discovered that it protects the integrity of machinery for maintaining a cell's energy level.
To find out if P7C3 could similarly stem aging-associated neuronal death and cognitive decline, the researchers gave the compound to aged rats. Rodents treated with P7C3 for two months significantly outperformed their placebo-treated peers on a water maze task, a standard assay of hippocampus-dependent learning. This was traced to a threefold higher-than-normal level of newborn neurons in the dentate gyrus of the treated animals. Rats were used instead of mice for this phase of the study because the genetically engineered mice could not swim.
Prolonged treatment of aged rats with P7C3 also enhanced the birth of new neurons. "Aged rats normally show a decline in neurogenesis associated with an inability to form new memories and learn tasks," Pieper explained.

In their study, rats treated with P7C3 each day showed evidence of an increase in the formation of newborn neurons and significant improvements in their ability to swim to the location of a missing platform, a standardized test of learning and memory in rats.

The researchers pinpointed a derivative of P7C3, called A20, which is even more protective than the parent compound. They also produced evidence suggesting that two other neuroprotective compounds eyed as possible Alzheimer's cures may work through the same mechanism as P7C3. The A20 derivative proved 300 times more potent than one of these compounds currently in clinical trials for Alzheimer's disease. This suggested that even more potent neuroprotective agents could potentially be discovered using the same methods. Following up on these leads, the researchers are now searching for the molecular target of P7C3 -- key to discovering the underlying neuroprotective mechanism. _ScienceDaily

The study was two-tiered: First the scientists screened over a thousand small molecules in knockout mice, to find the one that provided the best protection for new hippocampal neurons. Then they tested the compound in senescent rats, looking for both behavioural improvements and better survival of new hippocampal neurons. They were successful on all counts.

H/T Brian Wang of NextBigFuture

Cross-posted to Al Fin

Bortezomib Prunes Inflammatory T Cells: Hope for Inflammatory Diseases that Make the Young Old and Make the Old Want to Die

Inflammatory diseases such as arthritis, inflammatory bowel disease, multiple sclerosis, lupus, and many more, can strike at any time. Such diseases can create such suffering and disability that they make young people old very quickly, and can make old people wish they were dead.

A fairly new drug in the proteasome inhibitor class, Bortezomib, is used to treat a cancer of the bone marrow cells, multiple myeloma. But now, scientists have discovered a new use for Bortezomib: killing off active and proliferating T cells that cause so much damage in inflammatory diseases -- while leaving the resting T cells alone.

Those looking for a new treatment for a range of inflammatory diseases like arthritis, multiple sclerosis, inflammatory bowel disease, and lupus may need to look no further than a drug already available for treating cancer. In a research report published in the July 2010 print issue of the Journal of Leukocyte Biology (http://www.jleukbio.org), Japanese scientists use mice to show that bortezomib, currently used to treat cancers that affect white blood cells, induces cell death only in harmful (active and proliferating) T cells, leaving the rest unharmed. If the results prove true in humans, it offers hope that this drugs or others similar to it might be used to treat inflammatory diseases without the side effects of current drugs that affect all T cells equally.

"Unfortunately, there are a lot of people who are suffering from autoimmune and inflammatory disease," said Koichi Yanaba, M.D., Ph.D., a scientist from the Department of Dermatology at Nagasaki University Graduate School of Biomedical Sciences who was involved in the research. "We believe that this new-type remedy for autoimmune and inflammatory disease could successfully treat them in the near future."

To make this discovery, scientists used two groups of mice—the first treated with bortezomib and the second with saline. Researchers induced contact hypersensitivity reaction with oxazolone, a chemical allergen used for immunological experiments and found that bortezomib significantly inhibited the contact hypersensitivity responses. Results strongly suggest that bortezomib treatment enhanced T cell death by inhibiting NF-kappa B activation, which plays a key role in regulating the immune response to infection. This in turn led to the suppression of inflammatory responses in immune cells by reducing interferon-gamma production. _Eurekalert

Inflammation complicates many diseases of old age, including Alzheimer's, heart disease, lung and other respiratory diseases, digestive system diseases, and so on. Finding better and more specific treatments for blocking excessive inflammation while allowing normal immune function to continue, would extend life for many and reduce morbidity for many more.

Another Way to Add Years to Your Life

Physorg
Most people spend a third of their lives sleeping. Doing without sleep does not seem to work well, in terms of achieving optimal focus and concentration. The brain seems to need that "down time" for some reason. This may be the reason:

Levels of adenosine triphosphate (ATP), the energy currency of cells, in rats increased in four key brain regions normally active during wakefulness. Shown here is the energy surge measured in the frontal cortex, a brain region associated with higher-level thinking. Credit: Courtesy, with permission: Dworak et al. The Journal of Neuroscience 2010.

In the initial stages of sleep, energy levels increase dramatically in brain regions found to be active during waking hours, according to new research in the June 30 issue of the Journal of Neuroscience. These results suggest that a surge of cellular energy may replenish brain processes needed to function normally while awake.

The authors measured levels of adenosine triphosphate (ATP), the energy currency of cells, in rats. They found that ATP levels in four key brain regions normally active during wakefulness increased when the rats were in non-REM sleep, but were accompanied by an overall decrease in brain activity. When the animals were awake, ATP levels were steady. When the rats were gently nudged to stay awake three or six hours past their normal sleep times, there was no increase in ATP.
The authors conclude that sleep is necessary for this ATP energy surge, as keeping the rats awake prevented the surge. The energy increase may then power restorative processes absent during wakefulness, because brain cells consume large amounts of energy just performing daily waking functions. _Physorg

Now that scientists have a clue as to where to look for sleep's regenerative effects on the brain, they can begin to devise alternative ways of stimulating that regeneration -- other than to consume 1/3 of every 24 hour day for that purpose.

Alternative schedules of sleep / wake cycles, napping strategies, electromagnetic stimulation, nutritional or exercise strategies, etc -- there is likely to be workable ways by which an individual could achieve brain ATP regeneration AND redeem some of those 8 hours of sleep for productive or leisure activity. More living, in other words, without endangering one's health.

It is a mere glimpse behind the curtain of sleep, but it could prove to be a useful one. Two extra hours of productive wakefulness over 30 years can give you two and a half extra years of intentional living. If you are just as rested and just as healthy, then there are few reasons not to have more awake time.

Printing Out New Organs and Other Adventures in New Biology

It may not be long before severely burned persons will be able to lie back and watch while an entirely new skin is printed onto their body -- saving their lives.

The same printer technology that sits on your desk could soon be a common fixture in rebuilding human tissue, treating burns by laying down layers of a patients' own skin or even rebuilding whole organs.

A team at Wake Forest University has built a "bioprinter" that uses cells instead of ink. It even uses an ordinary, off-the-shelf printhead, connected to test tubes full of different cell types instead of wells full of colored inks.

Led by Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine in Winston–Salem, N.C., the team is working on treating burns. Such wounds can be hard to treat, because in severe cases there might not be enough healthy skin on the patient to harvest or culture for a graft.Grafting skin to cover burn wounds is also important for preventing infections, which can be a source of complications. Printing out cells grown in culture would eliminate these problems. Another application is repairing scar tissue.

The breakthrough in using bioprinting for tissue regeneration is the gel used to contain the cells: The mixture must hold the cells in place when they are laid down as well as provide a viable medium where they can be kept alive while they are held in the reservoirs. "It took us seven years," he says. "There's lots of trial and error; this isn't trivial chemistry," he adds.

For building tissue, several printing methods were tried, including three-dimensional CAD and laser printing. But once the group hit on the inkjet method, it turned out to work so well that some of the early work on building tissue was done on modified inkjet printers from a local office supply store.

Other organs have been constructed from cultured cells, but they were built on a scaffolding to give them their three-dimensional shape. Skin doesn't require a matrix because it is relatively flat to begin with.

So far, the system has been tested on mice, which are given wounds similar to burns. Those that were treated with printer-generated cells healed in three weeks, whereas those that were allowed to recover naturally required five weeks. The researchers plan to test the system on bigger animals in the future. The technology is still in the early stages, Atala says. As of yet there is no timetable for human tests or for the publication of the mouse research results.

The Wake Forest group is not just working on skin. Bone tissue and a two-chambered mouse heart have both been successfully printed. The heart was stimulated to beat when the cells were shocked with electricity, and the printed bones have been implanted in mice. _SciAm

Another approach to tissue regeneration is the use of biodegradable polymers as a scaffolding for the growth of replacement cells and tissues.

Here is an idea that is genuinely visionary -- which is exactly the sort of thinking we need to promote if we are ever to get to where we want to go. If we can take our biology to the level that allows us to grow living, breathing, thinking buildings that keep us comfortable and safe, imagine the level of accomplishment that human tissue engineering will have achieved.

A healthy, vibrant, and expansive society requires the best from all of its citizens. We cannot afford to be overly focused upon just one goal. We need to also be developing ideas and processes that may have no immediate use -- but which may indeed be earthshaking and earth saving sometime in the future.

Regenerative Medicine Roadmap

PDFRegen-RoadmapPDF
FightAging presents a look at what it describes as "The Dawn of the Age of Tissue Engineering", and presents a roadmap of regenerative medicine in PDF format. via Brian Wang

Regenerative medicine is one of several different approaches to life extension and improved human longevity.

Cell therapy involves the adding of younger or progenitor cells, the removal of senescent or destructive cells, and the genetic reprogramming of cells in situ. New and reprogrammed cells then grow within the pre-existing matrix.

Tissue engineering involves the growth of tissues or entire organs within artificial scaffolding. This growth may occur outside the body (for later transplant) or inside the body with in situ tissue engineering.

Cell therapy is the easier approach, but may take several decades of development to achieve the regenerative power that tissue engineering promises to provide within one decade.

Hormonal and growth factor regenerative medicine use chemicals to alter the cells from the outside, in a therapeutic sequence. This approach is even easier than cell therapy, but is also more limited.

There are other regenerative therapies which work via the immune system, and via epigenetic systems, and some of these will come into use within the next decade or two.

Other life extension strategies -- such as cryonics, mitochondrial rejuvenation, technological prostheses, and the total redesign of the human body -- will continue to receive varying levels of support. One should also keep an eye on SENS.

Thymosin Beta 4 Helps Regenerate Damaged Brain in Rats

The small protein thymosin beta 4 has multiple functions: it moonlights to repair injured tissues [6], has anti-inflammatory efficacy in monocyte/macrophages [7], promotes wound healing [8] and mediates angiogenesis [9]. Tβ4 has been also shown to play a relevant role during the development of different neural cell types in the rat brain [10]. In particular, Tβ4 plays a neurotrophic and antiapoptotic role during the development of the nervous system [11]. __PLoSONE

New research to be reported June 3 at the Annual Meeting of the Society for Academic Emergency Medicine in Phoenix, showed that in adult rats, thymosin beta-4 assisted in the repair of nerve fibres in the brain and in growing new blood vessels.

A synthetic version of a naturally occurring peptide promoted the creation of new blood vessels and repaired damaged nerve cells in lab animals, according to researchers at Henry Ford Hospital in Detroit.

"This successful experiment holds promise for treating clot-induced strokes in humans," says study lead author Daniel C. Morris, M.D., senior staff physician in the Department of Emergency Medicine at Henry Ford Hospital. "Neurorestorative therapy is the next frontier in the treatment of stroke." _SD

This is a potentially important finding for regenerative medicine, given how common cerebral vascular accident is in humans, and how dismal the prognosis typically is afterward.

Thymosin beta-4 is an immune modulating protein, which demonstrates once again how important the brain and the immune system are to one another. Given that Thymosin beta-4 is not a growth factor, as such, it will be important to generate a picture of the entire mechanism involved, for a complete understanding of potential therapies for brain damage, using this protein.

Neural Stimulators Control Inflammatory Processes

Scientists have known about the connection between the mind-brain and the immune system for many decades. From the "laughter cure" devised by Norman Cousins to mitigate a severe inflammatory disease to the decades old scientific discipline of psychoneuroimmunology, the importance of the connection between the brain and the immune system has been known. A malfunctioning immune system leads to both suffering and an early death, so discovering better ways to dampen an out of control immune response is vital to achieving long and healthy lives.

But finding the best way of controlling immune function by way of the brain has not always been easy. One of the latest attempts at such control comes from a business startup in Boston called Setpoint Medical.

The technology is based on a decade of research elucidating how the brain controls the immune system, particularly inflammation. The treatment has not yet been tested in patients, but based on animal research, scientists hope it will provide an alternative treatment that is more effective and have fewer side effects than existing drugs.

...Over the last decade, Kevin Tracey, an immunologist and neurosurgeon at the Feinstein Institute for Medical Research in Manhasset, NY, has shown that inflammation is controlled in part by the vagus nerve, which carries signals between the brain and a number of visceral organs. Most notably for immune function, it makes direct connections to the spleen, which houses different types of immune cells poised for release at times of infection.

Numerous animal studies have shown that stimulating the vagus nerve can put a brake on the immune system, stopping the rapid recruitment of immune cells to the site of injury or infection. "Think of it as a thermostat for the immune system," says James Broderick, interim president of the company and a partner at Morgenthaler Ventures, Setpoint's key investor. "This reflex puts a damper on the immune system."

The effect is similar to that of a popular class of drugs, called TNF alpha blockers, used to treat arthritis and other autoimmune diseases. These drugs block the release of an immune signaling molecule that is central to inducing inflammation. While they work effectively in 50 to 70 percent of patients, the drugs can lose their effectiveness over time and have been linked to some serious side effects, such as infection and cancer. Vagus nerve stimulation blocks both the signal molecule and other cytokines involved in inflammation. _TechnologyReview

This novel approach to treating autoimmune diseases and hyper-immune responses may be used instead of drug treatment, or along with drug treatment to allow lower doses of drugs.

Brain Cell Regeneration Using Reprogrammed Astroglia

The brain consists of two major cell types: neurons, which transmit information, and glial cells, which support and protect neurons. Interestingly, evidence suggests that some glial cells, including astroglia, can be directly converted into neurons by specific proteins, a transformation that may aid in the functional repair of damaged brain tissue. However, in order for the repaired brain areas to function properly, it is important that astroglia be directed into appropriate neuronal subclasses. In this study, we show that non-neurogenic astroglia from the cerebral cortex can be reprogrammed in vitro using just a single transcription factor to yield fully functional excitatory or inhibitory neurons. We achieved this result through forced expression of the same transcription factors that instruct the genesis of these distinct neuronal subtypes during embryonic forebrain development. Moreover we demonstrate that reactive astroglia isolated from the adult cortex after local injury can be reprogrammed into synapse-forming excitatory or inhibitory neurons following a similar strategy. Our findings provide evidence that endogenous glial cells may prove a promising strategy for replacing neurons that have degenerated due to trauma or disease. _PLOS

Scientists from the Helmholtz Center and Ludwig-Maximilians University in Munich, have used a virus to reprogram brain helper cells -- astroglia -- into actual neurons. They were able to convert astroglia from early post-natal and adult mouse brains into either excitatory or inhibitory neurons, depending upon the transcription factors which were introduced.

The study adds to growing evidence that certain cell types can be transformed directly into other cell types without first being converted into stem cells. Researchers have previously transformed skin cells into neurons, and one type of pancreatic cell into another. Marius Wernig, a coauthor of the skin cell study and a stem cell biologist at Stanford University, says there's a growing awareness that it may not be necessary to erase a cell's existing identity before giving it a new one.

...this latest study "means that these astroglial cells could be converted in the brain" without the need for a transplant. Berninger says that one of the next challenges is to determine whether these reprogrammed neurons can survive and function in a living brain.

Fortunately, the brain seems to have a ready source of astroglia. When the brain is injured, these cells proliferate, similar to the way the skin repairs itself after a wound. The researchers found they could also derive neurons from injury-induced astroglia taken from the brains of adult mice. _TechnologyReview

More:

we first aimed at a more potent neuronal reprogramming by inducing higher and more persistent expression of neurogenic fate determinants in astroglial cells. This allowed us not only to obtain fully functional neurons that also establish synapses from astroglial cells in vitro but also to demonstrate that distinct neurogenic transcription factors, such as on the one hand Neurog2 and on the other Dlx2 alone or in combination with Mash1, can indeed instruct the selective generation of different neuronal subtypes, such as glutamatergic and GABAergic neurons, respectively. Moreover, we found that the reprogramming efficiency of postnatal cortical astroglia towards GABAergic neurons by Dlx2 could be enhanced by first expanding the astroglial cells under neurosphere conditions prior to forced expression of Dlx2. Given that following brain injury reactive astroglia from the adult cerebral cortex de-differentiate, resume proliferation, and can give rise to self-renewing neurospheres in vitro [16], we finally show that neuronal reprogramming and subtype specification are not restricted to postnatal stages but can also be achieved from adult cortical astroglia responding to injury. _PLOS

The findings are a striking reminder that nature offers us many more possibilities than we can presently conceive of. But perhaps we will grow in our conceptual capacity, over time.

The possibility of regenerating brain tissue in situ -- without the need for inserting new cells from elsewhere -- offers new hope for brain trauma, infection, infarct, atrophy, and senility. But it also offers a distinctly new possibility which most observors are not quite ready to think about -- much less discuss.

I am referring to the possibility of growing entirely new neural networks in situ, from astroglia. The possibility that humans can induce their own brains to create entirely new brain centers and pathways, using more advanced forms of such techniques, should not be overlooked.

There is currently a race between biological methods of repairing and enhancing human organs, and technological methods of compensating for organ damage or loss -- the cyborg approach. A cyborg may utilise nano-technological enhancement, and thus manifest no outward sign of distinction from standard normal humans. The same would be true for most biological enhancements or remediation.

This lack of overt differences between ordinary persons and enhanced persons is quite important to most military uses of enhanced individuals, and to virtually all covert uses by government and other organisations.

But these tools of transformation are not likely to remain limited to deep pocketed groups and individuals. Garage biohackers are not as uncommon as you might think, and are performing a similar service for bio-hacking as the garage techno-hackers performed for microcomputers in the early days. And it is also extremely likely that persons involved in expensive and large scale research into bio-transformation technologies will set off on their own as they discover the ability to profit from their technical knowledge and skills.

Cross-posted at Al Fin

Tricks of Epigenetic Memory

It is common knowledge that a person's memory tends to get a bit foggy as he ages. A young person's memory tends to be crisper and quicker than that of a person in senescence. But it is possible that there is a means within our grasp by which we can turn back the clock in the aging brain -- back to a time of quicker and clearer recall, and a stronger grasp of new knowledge.

A new study published in Science sheds some light on how “memory disturbances” in an aging mouse brain are associated with altered “hippocampal chromatin plasticity” — the combination of DNA, histones, and other proteins that make up the chromosomes associated with the hippocampus. Specifically, the study describes an acetyl genetic switch that produces memory impairment in aging 16-month-old mice. Because the acetyl wasn’t present in young 3-month-old mice, the study concludes that it acts as a switch for a cluster of learning and memory genes.

...Dr. Fischer’s research shows that when young mice are learning, an acetyl group binds to a particular point on the histone protein. The cluster of learning and memory genes on the surrounding DNA ends up close to the acetyl group. This acetyl group was missing in the older mice that had been given the same tasks. By injecting an enzyme known to encourage acetyl groups to bind to any kind of histone molecule, Fischer’s team flipped the acetyl genetic switch to the “on” position in the older mice and their learning and memory performance became similar to that of 3-month-old mice. _hplus

More:

Dr Fischer, of the European Neuroscience Institute in Goettingen, Germany, pinpointed a tiny protein called H4K12 that controls genes key to memory and learning in the mouse brain.

...In an accompanying article, Professor David Sweatt , a U.S. neurobiologist, said that turning on H4K12 was likely to help with both Alzheimer's and age-related memory loss.
He said the German results 'provide important proof of principle that this might be a viable approach to therapeutic interventions in ageing'.
'These studies will hopefully lead to more effective prevention strategies to improve quality of life in the aged, as well as contribute to a better understanding of memory function,' he added.
The treatment of other brain conditions, such as schizophrenia and Parkinson's disease, could be improved by finding other switches that act in a similar way.
Dr Marie Janson, of the Alzheimer's Research Trust, said: 'Although in mice, this research gives us clues about how memories are formed and function in the brain.
'We now need to find out if the same processes happen in the human brain.
'This understanding is vital if we are to develop ways to protect the ageing brain from cognitive decline.
'Alzheimer's and other dementias are complex, with many things happening in the brain, so it's likely that we'll need several drugs to treat them effectively._DailyMail

Brain function is inextricably tied to genetic function. The relationship is certainly of a circular nature. If we are to learn to live long and fulfilling lives, we will need to undertand ourselves better, at a much deeper level than we once thought possible.

Stem Cells to Restore Your Hearing, Your Heart, Your Teeth

Stanford University researchers have developed a way to grow replacement "hair cells" for the inner ear, in mice. The hair cells are responsible for hearing, and the cumulative loss of hair cells over a lifetime result in permanent hearing loss. If humans could learn to regenerate the hair cells in the inner ear, hearing loss could be reversed without the need for electronic devices such as cochlear implants or hearing aids. Source via Brian Wang

Geron scientists have demonstrated the safety of GRNCM1 (cardiomyocites or stem cells) for replacing damaged heart tissue. This treatment, once approved, is likely to be used to treat chronic heart failure -- a significant cause of death and disability worldwide.
Source 1 (via Brian Wang), Source 2

Columbia University researchers are developing a method for growing replacement teeth "in place", inside the actual socket of the lost tooth. The method utilises stem cells to re-grow the tooth along with accompanying soft tissue support. This approach will do away with the need to use hardware implants, or to grow teeth outside the body in culture media.
Source via Brian Wang

The re-growth of body organs in place -- using the original tissue matrix as a scaffolding -- is a safer approach than re-growing organs outside the body, then surgically implanting them. Both approaches will probably become common, but in circumstances where in situ stem cell replacement is effective, most persons will likely opt for that approach.

Stem Cells from Endometrial Tissue Reverse Parkinson's?

Scientists at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), have injected endometrial stem cells into the brains of mice with an induced form of Parkinson's Disease. The injected stem cells began producing dopamine -- the neurotransmitter that is deficient in Parkinson's.

The finding raises the possibility that women with Parkinson's disease could serve as their own stem cell donors. Similarly, because endometrial stem cells are readily available and easy to collect, banks of endometrial stem cells could be stored for men and women with Parkinson's disease.

"These early results are encouraging," said Alan E. Guttmacher, M.D., acting director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NIH Institute that funded the study. "Endometrial stem cells are widely available, easy to access and appear to take on the characteristics of nervous system tissue readily."

Parkinson's disease results from a loss of brain cells that produce the chemical messenger dopamine, which aids the transmission of brain signals that coordinate movement. This is the first time that researchers have successfully transplanted stem cells derived from the endometrium, or the lining of the uterus, into another kind of tissue (the brain) and shown that these cells can develop into cells with the properties of that tissue. The findings appear online in the Journal of Cellular and Molecular Medicine. _SD

An optimal form of brain regeneration would likely combine the use of exogenous growth factors and stem cells, along with the stimulation of endogenous stem cell and growth factor production. There is a lot to be learned about how the brain works normally, and what goes wrong in degenerative conditions, trauma, ischemia, and aging.

Even an Old Hippocampus Continues Making New Neurons

The brain maintains neuronal stem cells throughout life, according to scientists at Max Planck Institute who studied the phenomenon of lifelong neurogenesis in mouse brains.

The precise factors that influence the reactivation of dormant stem cells are not yet clear. The cells can, however, be stimulated to divide again. The scientists observed more newborn hippocampal neurons in physically active mice than in their inactive counterparts. "Consequently, running promotes the formation of new neurons," says Verdon Taylor. Pathological brain activity, for example that which occurs during epileptic seizures, also triggers the division of the neuronal stem cells.

...The presence of neurons that are formed over the course of life has also been demonstrated in the human hippocamus. Therefore, scientists suspect that different types of active and inactive stem cells also arise in the human brain. It is possible that inactive stem cells in humans can also be activated in a similar way to inactive stem cells in mice. _Physorg

If increased physical activity can stimulate new nerve cell generation, a strong argument could be made for encouraging a more active physical regimen throughout a person's lifetime. Such a finding argues for the importance of physical rehabilitation as a treatment for neurodegenerative diseases, and after a stroke or other necrotising brain injury.

Making new neurons is not the same thing as being sure the neurons are healthy and optimally functioning. Scientists are learning more about the micro-differences between healthy neurons and those that are not so healthy. The delicate micro-structures called dentritic trees or arbours, are important to good communication within the neuronal networks. And the health of these dendritic trees depends upon optimal quantities of certain cell proteins -- which are under genetic control.

And that genetic control is of course under the control of transcription factors which are influenced by a number of other things -- some under genetic control, and some influenced by the evironment.

Finding more ways that a person can optimise the generation of healthy new neurons -- and to maintain the health of those in existence -- will be worth all the time it will take.

A Second Level of Gene Transcription Control

Controlling gene expression is an important key to controlling ageing, cancer, diseases of degeneration and autoimmunity, and virtually any other mechanism of human health and pathology. As scientist learn more about the mechanisms of gene expression, they also discover new ways of intervening to prevent or treat disease. The following article discusses the ongoing clarification of an important added complexity of gene expression that will certainly be exploited for good effect before long.

A new study published online today (April 29) in Cell helps drive home just how widespread this second level of gene control is, and implicates a cancer-causing transcription factor as a major player in the process.

"This is another piece in the puzzle that demonstrates controlling the elongation phase of transcription" -- the production of messenger RNA as the transcriptional apparatus propagates down the gene -- "is one of the more important control mechanisms," said biochemist David Price of the University of Iowa, who was not involved in the study. "[This] paper is going to help convince the field that this is just the way it is."

Scientists once believed that transcription factors promoted gene expression simply by recruiting RNA polymerase II (Pol II) machinery to the promoter region of their target genes, and letting the Pol II take over from there. But over the last 20 years, several lines of evidence indicated that once bound to the promoter, Pol II pauses, or stalls, just a little ways down the transcript, and needs another signal (such as a transcription factor) to continue transcribing the gene. Recent evidence suggests that this pause is a widespread phenomenon in the genome, but "there's been some reluctance in the transcription community to accept that there are these polymerases poised [just past the start site] all throughout the human genome," Price said.

Exploring the role of this mechanism of gene control in mouse embryonic stem cells (ESCs), molecular biologist Richard Young of the Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology and his colleagues have all but eliminated that doubt. They found evidence of paused polymerases on the vast majority of genes -- both those actively being transcribed and those that remained silent.

"We're thinking now that at all genes where RNA polymerase II initiates transcription, there is a pause step," Young said. "So even genes that are being currently and actively transcribed, polymerase initiates [transcription], but must go through this pause checkpoint before it's allowed to proceed to elongation."

The team further showed that the well-studied transcription factor c-Myc, which is involved in cell self-renewal and proliferation and has been implicated in 15-30 percent of human cancers, is an example of the additional factor needed to push Pol II past the pause. Instead of promoting gene expression by recruiting Pol II to the genes, c-Myc appears to release already-initiated polymerases from this paused stage. It does so by recruiting a protein known as positive transcription elongation factor b (P-TEPb) to release the Pol II to finish what it started.

Understanding the details of this mechanism of gene control could thus have important implications for the treatment of a variety of ailments, said molecular biologist and clinician B. Matija Peterlin of the University of California, San Francisco, who also did not participate in the research. "I think it brings a whole new aspect to not just cancer [research] but" other diseases as well, Peterlin said. "If you attenuate the activity of P-TEFb, you might be able to [develop] a non-gene-modifying way treat a lot of human diseases."

P.B. Rahl, et al., "c-Myc regulates transcriptional pause release," Cell:141,1-14,2010.

Read more: More support for transcription trick - The Scientist - Magazine of the Life Sciences http://www.the-scientist.com/blog/display/57384/#ixzz0malxMCbC _the-scientist

Nano-Magnets Lead Stem Cells to Damaged Heart

A promising way of healing damaged heart tissue involves combining stem cells with nano-magnets.  The magnetised stem cells are then steered to the site of damage, using magnetic fields.

"Stem cell therapies show great promise as a treatment for heart injuries, but 24 hours after infusion, we found that less than 10 percent of the stem cells remain in the injured area," said Eduardo Marbán, M.D., director of the Cedars-Sinai Heart Institute. "Once injected into a patient's artery, many stem cells are lost due to the combination of tissue blood flow, which can wash out stem cells, and cardiac contraction, which can squeeze out stem cells. We needed to find a way to guide more of the cells directly to the area of the heart that we want to heal."
Marbán's team, including Ke Cheng, Ph.D. and other researchers, then began a new animal investigation, loading cardiac stem cells with micro-size iron particles. The iron-loaded cells were then injected into rats with a heart attack. When a toy magnet was placed externally above the heart and close to the damaged heart muscle, the stem cells clustered at the site of injury, retention of cells in the heart tripled, and the injected cells went on to heal the heart more effectively.
"Tissue viability is enhanced and heart function is greater with magnetic targeting," said Marbán, who holds the Mark Siegel Family Foundation Chair at the Cedars-Sinai Heart Institute and directs Cedars-Sinai's Board of Governors Heart Stem Cell Center. "This remarkably simple method could easily be coupled with current stem cell treatments to enhance their effectiveness." _Physorg

Image Source

The combination of stem cells with nanotechnology provides another synergistic surprise, loaded with hope for future cures and life extension potential.

Tomorrow's medical treatments will be more individualised, more targeted to specific systems and tissues. As a result, the collateral damage will be lessened, interventional dosing and exposure can be moderated, and a desired outcome can be made more likely.

Switching Off Cancer Using Nanoparticles

Cuanas
Scientists at Cal Tech in Pasadena have used targeted nanoparticles to alter the gene expression of cancer cells in human cancer patients. Their phase 1 clinical trial established the efficacy of their targeting approach and was published in the 21 March advanced online Nature.

Lead author Dr Mark E Davis, the Warren and Katharine Schlinger Professor of Chemical Engineering at Caltech, told the press that in principle:

"Every protein now is druggable because its inhibition is accomplished by destroying the mRNA."

"And we can go after mRNAs in a very designed way, given all the genomic data that are and will become available," he added.

However, as is often the case, what looks straightforward in theory is fraught with obstacles when you try and apply it in practice. One such difficulty, when trying to apply RNAi technology to humans is, how do you deliver such tiny, fragile molecules, the small interfering RNAs (siRNAs), to the tumors?

Senior author Dr Antoni Ribas, an associate professor of medicine and surgery and a researcher at UCLA's Jonsson Comprehensive Cancer Center, said:

"There are many cancer targets that can be efficiently blocked in the laboratory using siRNA, but blocking them in the clinic has been elusive."

Davis and colleagues had a solution: they had already been working on ways to deliver nucleic acids into cells before RNAi was discovered. They eventually came up with a method featuring four components, one of which is a unique polymer that can assemble itself into a targeted nanoparticle that carries siRNA.

Davis explained that their nanoparticles can take the siRNAs into the targeted site within the body, and when they reach their target, the cancer cells inside the tumor, the nanoparticles enter the cells and release the siRNAs.

The researchers used a new method developed at Caltech to find and image the nanoparticles inside cells biopsied from the tumors of several patients taking part in the trial.

They also found that the more nanoparticles a patient was given, the more were present in the tumor cells: thus establishing there was a dose-dependent response.

But what was even better, said Davis, was they found evidence the siRNAs had done their job: in the cells they analyzed, which had been targeted to prevent production of the cell-growth protein ribonucleotide reductase, they found the corresponding mRNA had been degraded. Thus effectively the siRNAs had silenced the gene that was fuelling cancer growth.

Davis explained that this was the first time that anyone has found an RNA fragment from patient cells showing that the RNAi mechanism had severed the mRNA at exactly the correct base:

"It proves that the RNA interference mechanism can happen using siRNA in a human," said Davis.

Ribas said:

"This research provides the first evidence that what works in the lab could help patients in the future by the specific delivery of siRNA using targeted nanoparticles."

"We can start thinking about targeting the untargetable," he added. _MedicalNews

As the authors say, this is just the beginning. Silencing gene expression by targeting the mRNA is only a temporary approach. If such treatment kills all of the cancer cells -- and leaves normal cells alone -- then being only temporary will not be an impediment.

But in many types of cancer -- and other disease -- it will not be enough merely to block the offensive mRNA. You will want to alter the DNA itself to put a permanent stop to the flow of a particular unwanted mRNA. That will require a different approach altogether.

The challenge is vast and seemingly unending. But it is worthwhile.

H/T Cuanas