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Friday, 27 February 2009

The future of medicine, 02, 2009

Today:

  1. Scrawny' gene keeps stem cells healthy
  2. Converting adult somatic cells to pluripotent stem cells using a single virus
  3. Scientists develop first examples of RNA that replicates itself indefinitely
  4. British first as baby born free of cancer gene
  5. Patient’s DNA May Be Signal to Tailor Medication

Scrawny' gene keeps stem cells healthy

(PhysOrg.com) -- Stem cells are the body's primal cells, retaining the youthful ability to develop into more specialized types of cells over many cycles of cell division. Scientists at the Carnegie Institution have identified a gene, named scrawny, that appears to be a key factor in keeping a variety of stem cells in their undifferentiated state.

In the study, Spradling, with colleagues Michael Buszczak and Shelley Paterno, determined that the fruit fly gene scrawny modifies a specific chromosomal protein, histone H2B, used by cells to package DNA into chromosomes. By controlling the proteins that wrap the genes, scrawny can silence genes that would otherwise cause a generalized cell to differentiate into a specific type of cell, such as a skin or intestinal cell.

The researchers observed the effects of scrawny on every major type of stem cell found in fruit flies.

Stem cells function as a repair system for the body. They maintain healthy tissues and organs by producing new cells to replenish dying cells and rebuild damaged tissues.

While the scrawny gene has so far only been identified in fruit flies, very similar genes that may carry out the same function are known to be present in all multicellular organisms, including humans. source

My comment: Not too much to say here-this is a piece of great research. I'm posting it, because this really is a step in the right direction for the stem-cell research. If you know that gene, you can manipulate it to either make the type of cells you need or to keep the stem cells intact for later use. That's great.

Converting adult somatic cells to pluripotent stem cells using a single virus

A Boston University School of Medicine-led research team has discovered a more efficient way to create induced Pluripotent Stem (iPS) cells, derived from mouse fibroblasts, by using a single virus vector instead of multiple viruses in the reprogramming process. The result is a powerful laboratory tool and a significant step toward the application of embryonic stem cell-like cells for clinical purposes such as the regeneration of organs damaged by inherited or degenerative diseases, including emphysema, diabetes, inflammatory bowel disease, and Alzheimer's Disease.

Prior research studies have required multiple retroviral vectors for reprogramming essentially a separate virus for each reprogramming gene (Oct4. Klf4, Sox2 and cMyc) that convert the cells from their adult, differentiated status to what amounts to an embryonic-like state.

However, the high number of genomic integrations that typically occurs when multiple viruses are used for reprogramming, poses a safety risk in humans, as some of these genes can cause cancer.

The major milestone the six-member research team, led by Gustavo Mostoslavsky, Boston University, achieved was combining the four vectors into a single "stem cell cassette"(named STEMCCA) containing all four genes.

With the STEMCCA vector, the researchers were able to generate iPS cells more 10 times more efficiently and several iPS clones were generated with a single viral integration. source

My comment: Again, not too much to say, except that this is a big advance and I can't wait to see where all those cool discoveries are taking us to.

Scientists develop first examples of RNA that replicates itself indefinitely

January 9th, 2009

Scientists from Scripps Research Institute have synthesized for the first time RNA enzymes that can replicate themselves without the help of any proteins or other cellular components, and the process proceeds indefinitely.

In the modern world, DNA carries the genetic sequence for advanced organisms, while RNA is dependent on DNA for performing its roles such as building proteins. But one prominent theory about the origins of life, called the RNA World model, postulates that because RNA can function as both a gene and an enzyme, RNA might have come before DNA and protein and acted as the ancestral molecule of life.

The goal of the researchers was to take one of the RNA enzymes already developed in the lab that could perform the basic chemistry of replication, and improve it to the point that it could drive efficient, perpetual self-replication.

The team was able to isolate an evolved version of the original enzyme that is a very efficient replicator. The improved enzyme fulfilled the primary goal of being able to undergo perpetual replication.

The replicating system actually involves two enzymes, each composed of two subunits and each functioning as a catalyst that assembles the other. The replication process is cyclic, in that the first enzyme binds the two subunits that comprise the second enzyme and joins them to make a new copy of the second enzyme; while the second enzyme similarly binds and joins the two subunits that comprise the first enzyme. In this way the two enzymes assemble each other — what is termed cross-replication. To make the process proceed indefinitely requires only a small starting amount of the two enzymes and a steady supply of the subunits.

Then the researchers mixed 12 different cross-replicating pairs, together with all of their constituent subunits, and allowed them to compete in a molecular test of survival of the fittest. Most of the time the replicating enzymes would breed true, but on occasion an enzyme would make a mistake by binding one of the subunits from one of the other replicating enzymes. When such "mutations" occurred, the resulting recombinant enzymes also were capable of sustained replication, with the most fit replicators growing in number to dominate the mixture. The research shows that the system can sustain molecular information, a form of heritability, and give rise to variations of itself in a way akin to Darwinian evolution. source

My comment: Two points here. First, as a decent SG fan, I get very uncomfortable hearing the word "replicator". And if you think about it, letting loose such RNAs might create the perfect virus. True, it's not straight-forward, but the little guys are really creative in terms of survival and all that RNA needs is a non-living thing to incoroporate it in its genome. Apart from that, I think this is a wonderful proof of evolution and gives us a new perspective in terms of creation of life. If you think about it, it's not that hard in a complex environment to obtain such life building blocks. And then, all you need to do is wait and see who's going to survive and what it's going to become.

British first as baby born free of cancer gene

January 9th, 2009

A mother who is the first woman in Britain to have a baby selected free of a gene which causes breast cancer has given birth succesfully, doctors said Friday.

The baby's 27-year-old mother, who wants to remain anonymous, decided to take the step because several of her husband's close female relatives suffered from breast cancer.

Any daughter born with the BRCA 1 gene has an 80 per cent risk of developing breast cancer and a 60 per cent chance of developing ovarian cancer -- as well as a 50 percent risk of passing on the anomaly to their own children.

Doctors said the parents were relieved to have a guarantee that the faulty gene would not be passed to their daughter.

"This little girl will not face the spectre of developing this genetic form of breast cancer or ovarian cancer in her adult life," said Paul Serhal, head of the Assisted Conception Unit at UCL Hospital.

The procedure was carried out using a technique known as pre-implantation genetic diagnosis which has already been used here to screen embryos resulting from in vitro fertilisation for disorders like cystic fibrosis.

It was given the green light in Britain in 2006.

The procedure is still relatively rare but has been used to screen embryos for breast cancer in the United States and Belgium. source

My comment: I think this is a great news. Yes, it's a bit scary to imagine parents selecting the gens of their children, but for me, ensuring a cancer-free life is more important, especially when the probability of developing it is 80%. This is very hight percentage and I think the mother of the baby did the best thing. Sure, there are many more types of cancer to endanger the future person, but every one down the wall counts.

Patient’s DNA May Be Signal to Tailor Medication

Experts say that most drugs, whatever the disease, work for only about half the people who take them. Not only is much of the nation’s approximately $300 billion annual drug spending wasted, but countless patients are being exposed unnecessarily to side effects.

No wonder so much hope is riding on the promise of “personalized medicine,” in which genetic screening and other tests give doctors more evidence for tailoring treatments to patients, potentially improving care and saving money.

Many policy experts are calling for more studies to compare the effectiveness of different treatments. One drawback is that such studies tend to be “one size fits all,” with the winning treatment recommended for everybody. Personalized medicine would go beyond that by determining which drug is best for which patient, rather than continuing to treat everyone the same in hopes of benefiting the fortunate few.

The colon cancer drugs Erbitux and Vectibix, for instance, do not work for the 40 percent of patients whose tumors have a particular genetic mutation. The Food and Drug Administration held a meeting this month to discuss whether patients should be tested to narrow use of the drugs, which cost $8,000 to $10,000 a month.

And a genetic test might help doctors determine the optimal dose of warfarin, a blood thinner used by millions of Americans. Tens of thousands of them are hospitalized each year because of internal bleeding from an overdose or a blood clot from an inadequate dose. The test typically costs $100 to $600.

For all the potential, experts see some formidable obstacles on the path to the promised land of personalized medicine.

The hurdles include drug makers, which can be reluctant to develop or encourage tests that may limit the use of their drugs. Insurers may not pay for tests, which can cost up to a few thousand dollars. For makers of the tests, which hope their business becomes one of health care’s next big growth industries, a major obstacle is proving that their products are accurate and useful. While drugs must prove themselves in clinical trials before they can be sold, there is no generally recognized process for evaluating genetic tests, many of which can be marketed by laboratories without F.D.A. approval.

Genentech, a developer of cancer drugs, petitioned the F.D.A. this month to regulate such tests. It warned of “safety risks for patients, as more treatment decisions are based in whole or in part on the claims made by such test makers.”

A cautionary case is Herceptin, a Genentech breast cancer drug that is considered the archetype of personalized medicine because it works only for women whose tumors have a particular genetic characteristic. But now, 10 years after Herceptin reached the market, scientists are finding that the various tests — some approved by the F.D.A., some not — can be inaccurate.

Moreover, doctors do not always conduct the tests or follow the results. source
My comment: Yeah, what a surprise that the drug makers will be against the personalized medicine. But i think we must support in every way such tests. That will save us both money and life and improving our life should be our number one priority. As for drug makers-that a wonderful opportunity to start producing drugs that actually work.



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