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.