Australian and American Researchers Team to Advance Regenerative Medicine Strategies

When humans can grow new organs to replace tired or damaged organs, we will transcend one of the reasons for too-early death: organ failure. Every advance in the field of regenerative medicine is a positive step toward that goal.

John Foster's Bio/Polymer Research Group at the University of NSW worked out in 2004 the correct wavelength of infra-red laser to seal sheets of the university's patented discovery, SurgiLux, over wounds.

Now Foster is teaming up with Stephen Badylak, pioneer of the extra-cellular matrix, at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. Badylak creates ECM from ground-up pig organs. It acts as a scaffolding material for wounds and can be absorbed by the body. Cells spontaneously regrow on it and adult stem cells are attracted from other parts of the body, developing into tissue similar to the original.

These scaffolds have helped more than one million people regrow cartilage, rebuild urethras and repair hernias.

Foster and Badylak hold high hopes for the marriage of their technologies now that Foster has been awarded aFulbright senior scholarship that will fund him for up to four months' work with Badylak's group from June next year. The aim is to develop the technology to support the surgical repair ofnerves. _Australian

Growing new cells and tissues in the proper mix of cell types with neurovascular and lymphatic support, will require precise methods and timing. Learning how to best attach the new cells, tissues, and organs to the rest of the body is a vital part of the regenerative picture.

Gamma Secretase Inhibitors: Meant for Alzheimer's but Also Helpful for Brain Trauma?

Georgetown University scientists have studied the use of gamma secretase inhibitors (GSIs) to prevent permanent brain injury after head trauma, in mice. GSIs prevent the formation of amyloid buildup in the brain, in order to prevent or mitigate the amyloid plaques of Alzheimer's disease.

Interestingly, amyloid also accumulates in the brains of persons with brain injuries -- even very young victims of head injury.

Researchers at Georgetown University Medical Center will publish their findings in an advance online publication of Nature Medicine.

They say the results suggest that this class of drugs could potentially do something no other drug has been able to do — prevent the long-term and continuing damage that often follows a serious injury to the brain.

That is because the agents, known as gamma secretase inhibitors, are designed to prevent buildup of amyloid, a toxic peptide found in the brain. This peptide clogs the brains of Alzheimer’s patients but it is also found in people who have died from traumatic brain injury, says the study’s lead author, neuroscientist Mark Burns, Ph.D, an assistant professor at GUMC.

“No one knows why it occurs, but abnormal amounts of amyloid plaque have been found during an autopsy in about a third of brain injury victims, some of whom were children who would ordinarily never have had these deposits,” says Burns. _PsychCentral

Amyloid deposits can begin building as soon as 1 day after injury -- demonstrating how dynamic a contribution amyloid may make to long term brain damage.

It is hoped that rapid diminution of amyloid deposits will lead to brain recovery in both Alzheimer's patients and in victims of traumatic brain injury. For mice, the treatment was successful in blocking permanent brain damage.

GSIs are currently investigational drugs. If they can demonstrate efficacy for both Alzheimer's and traumatic brain injury, clinicians can hope for a dual approval when the drugs are released.

Turbocharging Antibody Response to Cancer etc

The human immune system is a powerful deterrent to a wide range of diseases, including cancer. But it takes time to build an immunity to new diseases. Researchers at Scripps Research Institute have devised a synthetic adaptor that can generate an almost instant immune response to the protein target of one's choice.

Most vaccines - like those for measles or smallpox - prompt the immune system to build a standing army of antibodies against a virus or bacterium by injecting a deactivated version of the bug into the body.

But it can take weeks or months to build up immunity, and you have to catch people before they get infected. What's more, the approach doesn't always work - cancer and HIV vaccines have proved elusive.

So instead, Carlos Barbas and colleagues at the Scripps Research Institute in La Jolla, California, have developed dumb-bell shaped "adaptor" molecules that bind mouse antibodies to proteins on the surface of disease-causing agents, redirecting the antibodies' killing focus. In an earlier experiment they attached these molecules to a single kind of antibody in the lab, and injected these "retrofitted" antibodies into the mouse to kill tumour cells.

Now they have demonstrated that these synthetic molecules can bind many kinds of antibodies to cancer cells inside mice and reduce the size of implanted human tumours.

Four weeks after the molecules were injected, the colon tumours had shrunk by up to 90 per cent, and melanomas by 78 per cent (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0900147106). _NS

Even if this new immune therapy does not completely eradicate a tumour, by shrinking its size it gives the patient's medical team more time to chance upon the magic bullet treatment for that particular patient. Each person is different, so it is natural that a person's response to disease and therapy will be unique.

A Realistic Look at Obama's Stem Cell Order

President Obama's long anticipated and much heralded signing of new federal guidelines for the financing of embryonic stem cell research will help US scientists learn more of the mysteries of embryonic cell differentiation and manipulation. But in reality, the effect of the new rules will be far less significant for the future of regenerative medicine than most gullible news consumers will ever know.

.....the president’s support of embryonic stem cell research comes at a time when many advances have been made with other sorts of stem cells. The Japanese biologist Shinya Yamanaka found in 2007 that adult cells could be reprogrammed to an embryonic state with surprising ease. This technology “may eventually eclipse the embryonic stem cell lines for therapeutic as well as diagnostics applications,” Dr. Kriegstein said. For researchers, reprogramming an adult cell can be much more convenient, and there have never been any restrictions on working with adult stem cells.

For therapy, far off as that is, treating patients with their own cells would avoid the problem of immune rejection.

Members of Congress and advocates for fighting diseases have long spoken of human embryonic stem cell research as if it were a sure avenue to quick cures for intractable afflictions. Scientists have not publicly objected to such high-flown hopes, which have helped fuel new sources of grant money like the $3 billion initiative in California for stem cell research.

In private, however, many researchers have projected much more modest goals for embryonic stem cells. Their chief interest is to derive embryonic stem cell lines from patients with specific diseases, and by tracking the cells in the test tube to develop basic knowledge about how the disease develops.

Despite an F.D.A.-approved safety test of embryonic stem cells in spinal cord injury that the Geron Corporation began in January, many scientists believe that putting stem-cell-derived tissues into patients lies a long way off. Embryonic stem cells have their drawbacks. They cause tumors, and the adult cells derived from them may be rejected by the patient’s immune system. Furthermore, whatever disease process caused the patients’ tissue cells to die is likely to kill introduced cells as well. All these problems may be solvable, but so far none have been solved.

Restrictions on embryonic stem cell research originated with Congress, which, each year since in 1996, has forbidden the use of federal financing for any experiment in which a human embryo is destroyed. This includes the derivation of human stem cell lines from surplus fertility clinic embryos, first achieved by Dr. James Thomson of the University of Wisconsin in 1998.

President Clinton contemplated but never implemented a policy that would have allowed N.I.H.-financed researchers to study human embryonic stem cells derived by others. Research was able to begin only in August 2001, when President Bush, seeking a different way around the Congressional restriction, said researchers could use any lines established before that date.

Critics said the distinction between the Clinton and Bush policies lacked moral significance, given that each was intended to get around the Congressional ban, based on a religious and moral argument. The proposed Clinton policy amounted to: “Stealing is wrong, but it’s O.K. to use stolen property if someone else stole it.” The Bush policy was: “Stealing is wrong, but it’s O.K. to use stolen property if it was stolen before Aug. 9, 2001.”

Mr. Obama has put the proposed Clinton policy into effect, but Congressional restrictions remain. Researchers are still forbidden to use federal financing to derive new human embryonic stem cell lines. They will, however, be allowed to do research on new stem cell lines grown in a privately financed lab. _NYT

More research on embryonic stem cells will help scientists understand the intricate mechanisms of cell development. They will acquire a fabulous treasure trove of knowledge about many diseases -- both rare and less rare. The knowledge spinoffs from this research will stretch far beyond regenerative medicine (RM) to cancer treatments, life extension technologies other than RM, and a much deeper understanding of biological mechanisms in general.

But all of that would have occurred without that much celebrated penstroke yesterday. And it is undeniable that the flow of NIH funds to non-embryonic stem cell research has been a boon to technologies that are more immediately applicable to the everyday regenerative cell and tissue treatments of the future -- treatment using the patient's own cells.

Science under Obama is every bit as political as science under any other president -- and will probably only grow more political with time. Obama's promotion of carbon penalties (disguised as "cap and trade") are a politicised hyping of the pseudo science of catastrophic global warming from anthropogenic CO2. Obama's carbon hysteria-based political meddling in the energy industry is likely to make Americans far more miserable, leaving them with far less resources to deal with exigencies, than if he had done nothing at all.

So let's celebrate the abundant biological future that will eventually come to us via all the avenues of research being followed. And let us not fall for the hype surrounding the gilded age of Obamanation.

Taken from an earlier posting at Al Fin

More Engineered Stem Cell News

Toronto's Samuel Lunenfeld Research Institute at Mt. Sinai Hospital is the site of groundbreaking research on engineered stem cells.

"We hope that these stem cells will form the basis for treatment for many diseases and conditions that are currently considered incurable," said Dr. Nagy, Senior Investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Investigator at the McEwen Centre for Regenerative Medicine, and Canada Research Chair in Stem Cells and Regeneration. "This new method of generating stem cells does not require embryos as starting points and could be used to generate cells from many adult tissues such as a patient's own skin cells."

Dr. Nagy discovered a new method to create pluripotent stem cells (cells that can develop into most other cell types) without disrupting healthy genes. Dr. Nagy's method uses a novel wrapping procedure to deliver specific genes to reprogram cells into stem cells. Previous approaches required the use of viruses to deliver the required genes, a method that carries the risk of damaging the DNA. Dr. Nagy's method does not require viruses, and so overcomes a major hurdle for the future of safe, personalized stem cell therapies in humans.

"This research is a huge step forward on the path to new stem cell-based therapies and indicates that researchers at the Lunenfeld are at the leading edge of regenerative medicine," said Dr. Jim Woodgett, Director of Research for the Samuel Lunenfeld Research Institute of Mount Sinai Hospital. Regenerative medicine refers to enabling the human body to repair, replace, restore and regenerate its own damaged or diseased cells, tissues and organs. _PO

The new method avoids the risks of tumourogenesis that come with using viruses for reprogramming cells into stem cells. Various new and potent techniques of producing virtually any stem cell type from adult cells bring modern biomedicine ever closer to the ability to replace and / or rejuvenate virtually any tissues in the body -- using the person's own cells!

There is still much to be learned about the genetic switching mechanisms involved. Until we are certain that the re-programming techniques can truly provide safe, long-lived replacement cells for the various tissues of the body, we will need to continue experimenting with embryonic stem cell lines as well as with the re-programmed stem cells.

New Alzheimer's Disease Model Offers Hope for a New Array of Therapeutic Targets

Biomedical research is learning a great deal about how the brain works at the cellular level. Alzheimer's Disease, for example, is being seen more as an imbalance within normal cell processes -- like cancer. A better understanding of these processes should allow more precise targeting of drug research.

One of the mysteries of AD has been the normal function of the amyloid precursor protein (APP) which are concentrated at the points where neurons connect. Even though the sticky amyloid plaques which have been viewed as a hallmark sign of AD result from APP, it seems unlikely that APP exists simply to cause Alzheimer's disease. In their study, scientists from the Buck Institute and the CNRS (Centre Nationale de la Recherche Scientifique) show that APP binds to netrin-1, a protein that helps to guide nerves and their connections in the brain, as well as helping nerve cells to survive. When netrin-1 was given to mice that have a gene for Alzheimer's disease their symptoms were reversed, and the sticky amyloid was reduced. These results suggest that the long-held belief that AD is caused by brain cell damage inflicted by the amyloid plaques may be wrong; instead, it is beginning to appear that the disease stems from an imbalance between the normal making and breaking of connections in the brain, with netrin-1 supporting the connections and the amyloid breaking the connections -- both by binding to APP and activating normal cell programs. Not only did the netrin-1 binding to APP keep the nerve cells alive and connected, but it also shut down the production of the amyloid, all of which makes it an interesting potential therapeutic. _Scientistlive

In the past few decades, the therapeutic viewpoint toward Alzheimer's has paced the rapidly growing knowledge of the underlying mechanisms of the disease. Already we have gone through multiple generations of treatments, with several radically new treatments in the pipeline. If "netrin-1" or its analogues can be delivered to the proper brain regions, and can at least partially reverse both the histological and the clinical pathology in AD, we will not only have a better treatment, but we will have one more promising lead to follow.

New Stem Cell Hope For Parkinson's

Researchers in Bonn have developed a method of culturing an indefinite supply of replacement neural stem cells -- including the cells that fail in Parkinson's -- from a single embryonic source.

"The new cells, in contrast, serve as an inexhaustible source: they provide a supply of human neural cells over periods of months and years without demanding any recourse to supplementary embryonic stem cells", declares Professor Dr. Oliver Brüstle, head of the research team at the Institute for Reconstructive Neurobiology at Bonn University.

Using animal experiments, the researchers in Bonn provided direct proof that these artificially derived neural cells will also function. Transplanted into the brain of a mouse, these cells made contact with the recipient brain and were subsequently able both to send and receive signals. "This is the first direct evidence that neural cells derived from human stem cells are capable of synaptic integration in the brain", declares Dr. Philipp Koch, the original author of the study. The scientists in Bonn are now also hoping to exploit this inexhaustible cell source to study neurodegenerative diseases and possible active agents directly in human neural cells. _MNT

If scientists can prevent the rejection of donor stem cells, the pathway toward routine replacement of aging brain tissue is now being constructed. Adult induced pluripotent stem cells from the patient herself is the best means for preventing rejection of tissue and stem cell implants. But if embryonic cell and tissue banks are able to carry a large "on-demand" supply of suitable cells, they will be quite useful.

Clearly the promise of stem cell research applies to other diseases besides Parkinson's, and to other organs besides the brain.

The problem for the US -- where funding for the development of new embryonic stem cell lines is expected to be expanded -- is the overall economy. The new government appears not to understand how a market economy recovers from a recession -- a recession that was brought on by bad government policies to begin with. A helpful hint to Obama and Pelosi: get rid of those bad government policies! (CRA etc)

Interferon Makes Dormant Cells Vulnerable

Dormancy is an important protection mechanism of stem cells. First, it protects their genetic material from genetic alterations, which happen primarily during cell division. In addition, dormancy helps them escape attacks of many cytotoxins, which act only on dividing cells. _MNT

Many cancer stem cells are likewise dormant, which can protect them from chemotherapy. Waking these cancer stem cells up before chemotherapy is one way to kill more of them, and increasing chances for a remission. Interferon seems to wake stem cells up from a dormant state, and force them to divide. This makes them vulnerable to mutation and to cytotoxins.

Patients suffering from a type of blood cancer called chronic myelogenous leukemia who are treated with a drug called Gleevec almost always relapse after drug treatment has ended. Several patients were given interferon-alpha prior to the Gleevec treatment. Surprisingly, these patients experienced long relapse-free phases without any medication. "We believe that the leukemia stem cells were awakened by the interferon administration and, thus, were sensitized to elimination by Gleevec," Andreas Trumpp explains. _MNT

The other side of the story is that interferon makes normal stem cells vulnerable to cytotoxic agents, so that blood forming stem cells in the bone marrow will be killed by some chemotherapeutic agents such as 5-FU, if interferon is given first. This can cause severe anemia and death.

This knowledge can lead one to speculate about the effects of viral infections and natural interferon on stem cells in other locations, such as the brain. The constant infectious assault experienced in the tropics, for example, may lead to chronic depletion of stem cells with all of the failure of normal regeneration that such depletion implies.

Each scientific discovery becomes the trigger for new exploration. The contemporary human mind cannot keep up with the multiple ongoing chain reactions of knowledge, but computers should be of some help.

Skin Cells Programmed to Become Heart Cells

Using techniques of induced pluripotent stem cell conversion, scientists at the University of Wisconsin created heart cells out of skin cells. The idea is to take a person with heart failure, make functioning replacement heart cells from abundant skin cells, and give the person what is in essence a new heart.

"This is the first demonstration that human induced cells can form different types of heart cells in a dish," said study co-author Tim Kamp, a University of Wisconsin cell biologist.

The latest findings, published Thursday in Circulation Research, suggests that failing hearts might be mended.

"We didn't know whether they could form heart cells efficiently," said Kamp. "But they successfully formed heart cells with all the electrical and organizational properties we'd expect."

In the last few years, induced pluripotency has been hailed as an uncontroversial alternative to embryonic stem cells, production of which requires the destruction of embryos.

Reprogramming flakes of skin would be a far easier alternative. _Wired

Novel Alzheimer's Drugs Coming

• As many as 5.2 million people in the United States are living with Alzheimer’s.

• 10 million baby boomers will develop Alzheimer's in their lifetime.

• Every 71 seconds, someone develops Alzheimer’s.

• Alzheimer's is the sixth-leading cause of death.

• The direct and indirect costs of Alzheimer's and other dementias to Medicare, Medicaid and businesses amount to more than $148 billion each year. _Alz

The older you get, the more likely that you will suffer some form of cognitive impairment -- most likely Alzheimer's. With the aging of North America and the developed world, the need for better ways to diagnose and treat Alzheimer's is critical.

New cognitive tests are being developed to determine whether a person with early cognitive impairment can drive safely. Special MRI techniques can show the early tell-tale signs of Alzheimer brain atrophy.

On the treatment side, "brain games" that develop short term memory appear helpful in reversing early cognitive impairment.

Another hopeful bit of news is that Rember and Dimebon -- two novel drug treatments for Alzheimer's -- are working their way through human drug trials, and show some promise.

A bit further in the future is the promise of Ampakines. Cortex Pharmaceuticals is the foremost developers of Ampakines for a wide range of disorders -- including Alzheimer's in the long run.

Further into the future, an even wider array of drugs are being developed to target several pathological mechanisms that are believed to contribute to Alzheimer's.

The main question at this time appears to involve financing for drug discovery and testing in the midst of an international financial crisis. US governmental policies under the new administration suggest that US pharmaceutical research and research into other vital innovative technologies will be short-changed. New drug development may well move offshore from the US to East and South Asia, where capital is less likely to be diverted to non-productive ends.

It is ironic that just when a relaxation of stem cell research regulations occurs, that draconian economic re-structuring should threaten the future of technological development in the biosciences and most other high tech fields.

Genetically Modified Regenerative Skin Graft Material Designed to Resist Infection

Stratatech’s StrataGraft® tissue is a second-generation human skin substitute that exhibits normal human skin structure and function. It is manufactured using the company’s proprietary NIKS® human keratinocytes, which were discovered at the University of Wisconsin. Keratinocytes are the cells that make up approximately 90 percent of the epidermis, the outer layer of human skin. NIKS® cells are a consistent source of pathogen-free, non-tumor-producing, long-lived adult progenitor cells. These cells faithfully reproduce normal human skin tissue architecture and barrier function when cultured appropriately. _StratatechCorp.

Regenerative medicine company Stratatech Corporation has developed a genetically tweaked living skin substitute for use in skin grafting. The genetic modifications of the living skin replacement makes it far more resistant to infection than currently available skin graft materials -- including autologous skin grafts.

The anti-infective capacity of Stratatech’s genetically-engineered tissue, which is being developed and commercialized by the company as ExpressGraft™ Enhance skin substitute through a worldwide exclusive license from the Wisconsin Alumni Research Foundation, or WARF, is produced by genetically engineering the elevated expression of a naturally-occurring antimicrobial host defense peptide called hCAP-18/LL-37. hCAP-18/LL-37 was selected because of its broad antimicrobial activity against both Gram-positive and Gram-negative bacteria, including methicillin-resistant S. aureus (MRSA), vancomycin-resistant E. faecalis (VRE) and other antibiotic-resistant hospital-acquired infections, as well as some fungi and viruses. The enhanced tissue possesses a full-thickness structure and barrier function similar to that of native human skin. The cell type used to generate the ExpressGraft™ tissue has been demonstrated to be non-tumor-producing and free from detectable pathogens, characteristics critical for cell-based, regenerative medicine therapies for patient use.

“Bacterial infection is a substantial cause of skin graft rejection and additional health care costs,” said Lynn Allen-Hoffmann, Ph.D., Stratatech’s founder, chief scientific officer and chief executive. “The potent anti-infective capability Stratatech has engineered in our living human skin substitute can be an important tool in improving skin-injury patient outcomes, and reducing the incidence and expense of hospital-acquired infections. We look forward to beginning the clinical evaluation of our antimicrobial skin substitute in the near term.

...Stratatech’s genetically-engineered skin substitute was generated using a non-viral vector, or carrier. The company believes it is the first time a virus-free approach has been used to genetically modify a living, cell-based tissue substitute. The data published in Molecular Therapy demonstrate that the modified tissue contained 139-fold more anti-infective proteins called host defense peptides than unmodified tissue in vitro. _BusinessWire

This is only the beginning of genetically improved, artificially grown bio-replacement materials. This skin replacement product from Stratatech should do well in the marketplace if it lives up to its promotion. But expect competing products that improve on the ExpressGraft's performance to emerge before long. This graft material does not perfectly reproduce the full, intricate layered structure of natural skin. But it is a good start.

Other more intricately structured grown replacement parts should follow on rather quickly. We are entering the age of regenerative medicine, when body parts and tissues will be grown in labs, rather than being donated by accident and crime victims. If these replacements can be designed to be tougher than the original parts being replaced, all the better.

Not Over the Hill Yet, Baby!

From the journal Stem Cells: UCLA researchers have managed to program human induced pluripotent stem cells into the precursors of human reproductive cells -- eggs and sperm. As quoted in Biosingularity:

Theoretically, an infertile patient’s skin cells, for example, could be taken and reprogrammed into iPS cells, which, like embryonic stem cells, have the ability to become every cell type in the human body. Those cells could then be transformed into germ line precursor cells that would eventually become eggs and sperm. Clark cautioned, however, that scientists are still many years from using these cells in patients to treat infertility. There is still much to be learned about the process of making high quality germ cells in the lab.

In another important finding, Clark’s team discovered that the germ line cells generated from human iPS cells were not the same as the germ line cells derived from human embryonic stem cells. Certain vital regulatory processes were not performed correctly in the human iPS derived germ cells, said Clark, an assistant professor of molecular, cell and developmental biology.

So it’s crucial, Clark contends, that work continue on the more controversial human embryonic stem cells that come from donated, excess material from in vitro fertilization that would otherwise be destroyed.

When germ cells are formed, they need to undergo a specific series of biological processes, an essential one being the regulation of imprinted genes. This is required for the germ cells to function correctly. If these processes are not performed the resulting eggs or sperm, are at high risk for not working as they should. This has significant consequences, given that the desired outcome is a healthy child. _Biosingularity

In other words, women past menopause or who have had their ovaries removed and men without testicles or with very low sperm counts will soon be able to produce viable sperm and eggs with the best of the twenty-somethings! Yes, I know that most people of a certain age do not want to have more children. But modern women often pursue their careers through the ages of optimal reproduction, and find that it's too late to have children by the time they feel they are ready. There are many other situations where persons might want to have their own children but can no longer produce the germ cells to do the job.

Eventually we will have artificial wombs that will take early embryos and support healthy gestation all the way to birth. By then, most of us will probably be living in good condition to 150 or beyond. Some may live long enough to raise three generations of offspring to adulthood. Why not, if you enjoy it and you can do it well?

Because by then, the question will not be "where will we put all these people?" The question will be, " where will we ever get enough people to do all the things that need to be done in this big universe?"

New Drug Class Promises a Medical Revolution

Image Source

Research into the effects of melanocortins has a huge potential to revolutionise medicine. Here are a few of the effects of melanocortin peptides on the brain:

Increase of motivation
Increase of attention
Improvement of short-term memory
Increase of visual retention
Lowering of auditory, gustatory and olfactory detection thresholds
Functional antagonism of opiate effects
Inhibition of feeding (satiety-inducing effect)
Antiinflammatory effect (sites of action: brain and immunocytes)
Antipyretic effect
Reversal of hypovolemic hypotension
Reversal of shock
Resuscitation after prolonged asphyxia
Improvement of recovery after traumatic brain lesions and spinal cord injuries
Delay of the aging-linked behavioural deficits
Beneficial influences in neurodegenerative disorders
Increase of regenerative capacity of peripheral nerves in postlesion repair
Improvement of diabetic and toxic neuropathies
Induction of spontaneous penile erections
Increase of [sexual] proceptivity and receptivity (in females)

_Pharmacological Research

Like I say, those are a few of the effects that have been discovered so far for the melanocortins (melanocyte stimulating hormones [MSH], ACTH). New drugs which can either block or stimulate these hormone receptors will likely revolutionise treatment for:

1. Alzheimer's and other neurodegenerative disease
2. Stroke
   
3. Diabetic Neuropathy
4. Hemorrhagic Shock
5. Sexual Dysfunction for males and females
   
6. Obesity
7. Anorexia and Cachexia
8. Depression
9. Anxiety
10. Various learning disorders

...and quite a few things more. It is only in the past decades that scientists have been able to distinguish different receptor types for the many peptides and neurotransmitters affecting the brain and nerves. Now, it looks like nothing can stop the steamroller of biomedical and biotech research -- except perhaps bad government that wastes precious resources on policies that have failed for many generations.

If you have an interest in any of the listed diseases or hormonal effects above, visit the linked article and skip down to the section that interests you particularly. It is a long review article that covers a wide range of effects and potential therapies. I strongly recommend learning to read scientific articles -- despite their dryness -- because any person who can draw meaning from the early stages of research can often see into the future, and profit from that vision. If you wait until "science journalists" spell it out and dumb it down for you, it may be too late.

When the baby revolutions of nanotechnology, biotechnology, information sciences, and cognitive sciences begin to grow up and converge, you will begin to understand how quickly things can change.

From al fin

Constructing New Infrastructure for Regeneration

Tissue scaffolds are the next big thing for implants of the future. Like the scaffolding we see on construction sites, the nano scaffolds are being created by Ko to reconstruct damaged tissue within the human body. Burn victims would benefit from scaffolds used to regenerate new skin. Those with failing heart valves or damaged nerves could count on scaffolds to regenerate these parts from within the patient’s own body. As healing progresses, the scaffold, being constructed from a biodegradable material, is absorbed and metabolized by the body while slowly releasing drugs to aid in the healing process. _CyborgAge

Almost every part of the body presents opportunities for scaffold bio-engineers to experiment. From the heart to the spine to the skin, all parts of the body eventually wear out and need to be replaced or regenerated. Scientists at UC Berkeley are taking an entirely new approach to bio-scaffold development. They are using viruses (bacteriophages) to build a proteinaceous infrastructure that promotes regeneration of nerve tissue.

Some biological engineers are using scaffolds made of polymers to try to mimic the supportive matrix of real tissue. Seung-Wuk Lee, a bioengineer at the University of California, Berkeley, has turned to viruses instead. "Viruses are smart materials," he says. "Once you construct the genome, you can make billions of phages, and they're self-replicating materials." The phage that Lee is working with, called M13, is long and thin like the protein fibers that make up the cellular matrices inside the body.

First, Lee and his colleague Anna Merzlyak genetically engineered M13 to display nerve-friendly proteins on their outer coats. These proteins are known to help nerve cells proliferate, adhere, and extend into long fiberlike shapes. Next, the researchers grew large numbers of the viruses in bacterial-cell hosts and dropped them into a solution containing neural-progenitor cells. These cells are more fully developed than stem cells but are still young and need coaxing to form new tissues. In the solution, the viruses align themselves like a liquid crystal, says Lee. He and Merzlyak used pipettes to inject the solution into agar, a Jell-O-like cell-culture medium, creating long, nerve-like fibers of the virus interspersed with cells. The progenitor cells then multiplied and grew the long branches characteristic of neurons. Lee says that the phage are well suited to making long, fiberlike structures such as nerve tissue but can also be made into more complex structures by varying their concentration or manipulating their position with a magnetic field. _TechnologyReview

Lee is planning to move to research inside live animals next. He is interested to discover how the immune systems of animals will react to viral construction workers hammering, drilling, and welding new infrastructure deep inside the organism.

For regenerative medicine to take that next big step forward, it will need the ability to grow specific infrastructure for every tissue and organ type that will be replaced or regenerated. Then, scientists will need to integrate growth factors and stem cells into the new matrix, and provide optimal nutrient solution. The prognosis for significant progress in this area is extremely favourable.

Nerve Regeneration Gene Pathway Discovered

Image Source

Research at the University of Utah has pinpointed specific genes in worms that appear to trigger nerve re-generation, and make old worms behave like younger friskier worms when the genes are over-expressed.

"One of the coolest things is we can improve regeneration," Nix says. "We originally looked at loss of this gene, dlk-1. The loss blocks regeneration. We can cut the nerve in these mutants and they don't regenerate. So we see worms with nerve stumps that don't do anything. But when we overproduce dlk-1 make an excess amount of it then we see an improvement in regeneration."

Jorgensen an investigator with the Howard Hughes Medical Institute says that "normally, young worms regenerate really well; old worms don't regenerate at all. What we can do by overexpressing dlk-1 is make old worms regenerate like young worms."

The chain of events the researchers identified as playing an essential role in nerve regeneration is known as a "MAP kinase pathway." Various MAP kinases play roles in cell division, response to stress, and cell specialization, Jorgensen says.

The pathway discovered in the new study "is unique in that it is not used by the nervous system during normal embryo development, yet it is absolutely required for regeneration," Bastiani says. "Most of us believed that virtually everything we found in regeneration also would be involved in development. So it is surprising."

He says while the dlk-1 gene is the most obvious target for new drugs to stimulate nerve regeneration, other genes in the pathway also could be potential targets. _GEN

Humans possess the same sets of genes that were studied in worms. It remains to be proven whether the genes have the same effect in humans for nerve regeneration, as in worms.

We are finding that older cells become leaky and let more damaging substances into their nuclear compartments, where DNA becomes damaged. Better means of preventing nerve damage and reversing that damage are beginning to come within the grasp of science.

Optical Coherence Tomography Provides an Active Window on the Brain

Optical Coherence Tomography (OCT) is a powerful new tool for monitoring both degenerative and malignant activities occurring deep within the brain -- by looking into the eyes. The OCT scanner uses two light beams (diodes or pulse lasers) to generate a 3d image of the depth of the retinas. This information tells medical specialists many different things about what is happening inside the skull.

One beam of light is fired at the tissue and another at a reference mirror. When the reflected beams have travelled an identical distance, interference will make their combined beam brighter than if the distances are different. So by reflecting one beam off of different layers of tissue, and moving the reference mirror until the combined reflected beam is brightest, the technique can measure the depths of each section of tissue and build up a detailed image of its structure. It has proved particularly useful in ophthalmology because the semi-transparent nature of retinal tissue makes it possible for OCT to penetrate to greater depths - up to several millimetres. When applied to the OND it can give information about both the shape and thickness of retinal nerve fibres, allowing even subtle changes to be tracked.

Such changes can be used to monitor the progression of diseases non-invasively and relatively cheaply. Unlike MRI, which is expensive and can require patients to remain still for an hour or more, OCT is increasingly available in clinics and can be carried out in a few minutes. "It's extremely inexpensive compared to other tests," says Valenti.

One possibility is to use OCT to monitor the effectiveness of treatments for neurodegenerative diseases, says Danesh-Meyer: "These drugs can have a lot of side effects, so if they are not having a benefit then you won't want to continue with them." _NS

The progress of brain tumours, multiple sclerosis, Alzheimer's, Parkinson's, and other brain diseases can be tracked over time using this non-invasive technique.

As the technology improves and allows for faster, less uncomfortable scans, it is likely that a routine baseline scan will be done on all adolescents as part of their permanent medical records. Should any new symptoms warrant it, later OCT scans can be compared with the baseline study to look for signs of brain pathology.

Longer lives mean more chances for new pathology. Pathology in the brain has been historically very hard and expensive to track over time. Newer technologies such as the OCT should allow medical scientists and practitioners to determine which persons need treatment, and which treatments provide the best result. The time saved by such new procedures should translate into a more functional lifespan.

SIRT 6 May Have Important Aging Role

SIRT1 has been the most studied of the SIRT family of proteins, but mice studies suggest that SIRT6 may also plan an important role in aging:

A formerly underappreciated member of the sirtuin family of proteins may hold the key to youthfulness and is the first sirtuin shown to specifically govern the activity of genes, scientists report.

Researchers from Stanford University report in the Jan. 9 Cell that SIRT6, a sibling of the aging-related protein SIRT1, is an important regulator of gene activity in mice.

“This is a big, big discovery,” says Raul Mostoslavsky, a chromatin biologist at the Massachusetts General Hospital Cancer Center and Harvard University Medical School in Boston. And one, he adds, that could shift some of the limelight away from SIRT1, a molecule implicated in the aging process.

“I’d say 95 percent of the literature is on SIRT1. I think that is going to change,” Mostoslavsky says. “People will start realizing that other sirtuins are probably important for regulating many biological functions.”

Mostoslavsky was not involved with the current study, led by Katrin Chua and Howard Chang of Stanford University, but he is familiar with all seven of the sirtuins found in mammals. He was the first to genetically engineer mice to lack each individual member of the sirtuin family. Mice missing SIRT6 develop normally for the first weeks of life, but then rapidly decline as if they are prematurely aging. The mice die by one month of age, ultimately of low blood sugar.

Last year, Chua’s group showed that SIRT6 is an enzyme that specifically removes a chemical called an acetyl group from a specific spot on a histone protein. Histones wrap DNA into a package that can fit inside the cell and are also important for controlling which genes turn on and off. Removing acetyl groups from histones generally shuts genes off.

Chua’s group has also previously shown that SIRT6 helps keep genomes stable and protects the ends of chromosomes, known as telomeres, from damage.

Now Chua’s and Chang’s groups together show that SIRT6 works with a master regulatory complex called NFkappa-B to govern activity of genes associated with aging, inflammation, immunity and metabolism. When SIRT6 is missing, NFkappa-B becomes hyperactive and turns up activity of aging-linked genes.

Reducing the amount of NFkappa-B in SIRT6-deficient mice restores normal life span and corrects many of the premature aging symptoms. But the mice still have low blood sugar, and many other genes not regulated by NFkappa-B show abnormal activity when SIRT6 is absent. _ScienceNews

Whether these findings are applicable to normal aging in mice or humans remains to be proven. Nevertheless, continued explication of the mechanisms of gene expression across the normal lifespan of mammals will eventually provide avenues to modifying the aging process.

Brain - Cooling Techniques

Scientists and physicians are developing new brain - cooling techniques to reduce morbidity after heart attacks (and presumably strokes) and to aid successful resuscitation after heart attacks. One device, like a reverse hair drying hood, cools the scalp and its blood vessels, achieving about 1 degree C cooling of the brain per hour. Another device sprays a refrigerant deep into the nose to indirectly cool arteries passing nearby, heading for the brain. The nasal device cools the brain by 2.4 degrees C per hour. A third device uses an icy slurry lavage into lung airways, to cool blood passing into the carotid arteries to the brain.

For some time, doctors have observed that cooling patients following a heart attack can reduce brain damage. Although they are not yet sure of the mechanism behind this effect, researchers suspect that cooling the brain by 4 °C, to around 33 °C, reduces the metabolism of brain cells, reducing their hunger for oxygen for the crucial moments during which blood is in short supply. Damage seems to be reduced even if the brain is only cooled once the heart has been restarted, suggesting that cooling may also slow the release of toxic chemicals from neurons and glial cells - a process called the ischaemic cascade, which triggers further brain-cell death up to 24 hours after a cardiac arrest or stroke.

Previously, doctors have induced "therapeutic hypothermia" by applying ice packs or cooling blankets to the whole body, or injecting cold saline solution into the veins. However, cooling the whole body can increase the risk of infection and pneumonia, so researchers are now building targeted devices that chill the brain directly.

...The ice slurry can cool the brain by 4 °C - the safe limit before damage is risked - in less than 15 minutes, says Kasza, who has so far tested the technique on pigs. His team is investigating whether their icy slurry could also be applied to the kidneys (see picture) and the heart during invasive surgery, to prevent damage to the organs when blood flow is suspended for the operation.

One of the main advantages of all the new techniques is that they are simple enough to apply before or immediately after resuscitation following a heart attack - minimising the delay between the heart malfunction and cooling the brain. "A paramedic could deliver the slurry," says Kasza.

What's more, a recent study in pigs suggests that immediate cooling with the RhinoChill device, besides reducing brain damage, could also improve the chances of success of the resuscitation itself, although it is not yet certain why this is. Sixteen pigs were given a heart attack, and then left for 15 minutes before CPR was applied to start their hearts again. Of the eight pigs cooled using the RhinoChill system during CPR, six survived, compared with just two of the eight who were left unchilled (Resuscitation, DOI: 10.1016/j.resuscitation.2008.03.087).

Rapid application of such techniques could be particularly good news for stroke victims. "Clot-busting drugs can only be administered after diagnosis and brain scans in the hospital," says Andrews. "But applying therapeutic cooling at the scene of the stroke could lengthen the time window in which the drugs are effective - before too much damage has occurred," he says. _NewScientist

These techniques are a far cry from the advanced cryonics and vitrification methods needed for long - term organismic storage or hibernation. But experiments with them, and experience using them should add to the knowledge needed to develop the longer - term methods.

Universal Aging Mechanism?

As an organism changes, its pattern of gene activation/deactivation and repair changes from a vibrant youthful pattern to a less efficient and effective senescent pattern. Harvard scientists are learning more about some of the underlying mechanisms behind this "genetic control shift of aging."

The researchers found in studies of mammalian stem cells that the protein SIRT1 controls the packaging of DNA into chromatin, thereby setting the youthful pattern of gene activity by keeping select genes switched off. In response to DNA damage, those SIRT1 proteins leave their posts to go off and assist in the necessary repairs. That change in SIRT1's job description leads to shifts in gene activity that parallel those seen in the aging mouse brain, they show. They suspect similar changes would also be found in other body tissues as well.

" The critical protein controls both which genes are off and on as well as DNA repair; it's used for both processes, and that's the catch," said David Sinclair of Harvard Medical School. "As cells accumulate DNA damage, the protein can't do both jobs sufficiently." Once SIRT1 loses control, gene activity goes haywire, a state of affairs that leads to symptoms associated with aging.

Sinclair's team also found what they consider to be good evidence that the aging process can be slowed. Mice with an excess of SIRT1 had an improved ability to repair DNA and prevent those unwanted changes in gene expression. The hope is that those improvements could be reproduced with a drug that stimulates SIRT1, they said. _Eurekalert

Permanent gene therapy to boost SIRT1 for both gene repair and maintaining a youthful gene activity pattern seems preferable to a daily pill or injection. In fact, genetic therapy will likely replace most pharmaceuticals as we learn more about the underlying physiology and pathology of our organisms. SIRT1 will be but a small part of the overall story of aging. But for now, it appears to be an important early step in our understanding.

MK-677, Oral Ghrelin Mimetic, Stimulates Youthful Pulsatile HGH Secretion in Elderly

Via NextBigFuture, this Annals of Internal Medicine article looks at the effect of an oral ghrelin mimetic on secretion of HGH, and various physical measurements such as muscle mass, visceral fat, etc.

Conclusion: Over 12 months, the ghrelin mimetic MK-677 enhanced pulsatile growth hormone secretion, significantly increased fat-free mass, and was generally well tolerated. Long-term functional and, ultimately, pharmacoeconomic, studies in elderly persons are indicated.

Previous trials in which growth hormone was administered to elderly persons were small, poorly controlled, or too short (8); in addition, growth hormone replacement does not restore pulsatile growth hormone secretion. MK-677, the first orally active ghrelin mimetic (a growth hormone secretagogue and growth hormone secretagogue–receptor agonist), increases pulsatile growth hormone secretion in older adults to levels observed in young adults (9, 10). Our primary objectives were to determine whether 25 mg of oral MK-677 daily would increase growth hormone and insulin-like growth factor I (IGF-I) levels in healthy older adults, prevent the decline in fat-free mass, and decrease abdominal visceral fat, with acceptable tolerability.

...Frailty is one of the scourges of elderly persons, and as researchers are beginning to learn about its causes, they are asking whether growth hormone deficiency is one of them. A systematic review (8) concluded that the risks of exogenous growth hormone outweigh the benefits and that it is not the long-sought solution to frailty. The promise of MK-677 is that it seems to restore endogenous growth hormone levels in a physiologic secretory pattern, unlike the single high-amplitude pulse observed after exogenous growth hormone administration. We believe that our study sets the stage for an adequately powered clinical trial of sufficient duration in a population vulnerable to frailty. _AnnalsIntMed

The effects of the more physiologic pattern of HGH secretion seen in MK-677 recipients vs. standard HGH replacement protocols, suggests that more indirect route of using an oral ghrelin mimetic may provide better long-term results.

The most significant adverse effect was an increase in appetite, which in many elderly might be seen as more of a positive miracle than an adverse effect. I encourage anyone interested to go to the article itself and read it in full. The complexity of homeostasis in the human organism should discourage simplistic and cavalier interventions for purposes of senescence mitigation. The study quoted above is a good example of a thoughtful and fairly comprehensive look at a measured intervention. The findings should be confirmed and integrated into the leading theories of senescence mitigation and reversal.