For the first time, scientists discovered that a specific type of human cell, generated from stem cells and transplanted into spinal cord injured rats, provide tremendous benefit, not only repairing damage to the nervous system but helping the animals regain locomotor function as well.

The study, published today in the journal PLoS ONE, focuses on human astrocytes - the major support cells in the central nervous system - and indicates that transplantation of these cells represents a potential new avenue for the treatment of spinal cord injuries and other central nervous system disorders.

Working together closely, research teams at the University of Colorado School of Medicine and University of Rochester Medical Center have made a major breakthrough in the use of human astrocytes for repairing injured spinal cords in rats.

"We've shown in previous research that the right types of rat astrocytes are beneficial, but this study brings it up to the human level, which is a huge step," said Chris Proschel, Ph.D., lead study author and assistant professor of Genetics at the University of Rochester Medical Center. "What's really striking is the robustness of the effect. Scientists have claimed repair of spinal cord injuries in rats before, but the benefits have been variable and rarely as strong as what we've seen with our transplants."

There is one caveat to the finding - not just any old astrocyte will do. Using stem cells known as human fetal glial precursor cells, researchers generated two types of astrocytes by switching on or off different signals in the cells. Once implanted in the animals, they discovered that one type of human astrocyte promoted significant recovery following spinal cord injury, while another did not.

"Our study is unique in showing that different types of human astrocytes, derived from the exact same population of human precursor cells, have completely different effects when it comes to repairing the injured spinal cord," noted Stephen Davies, Ph.D., first author and associate professor in the Department of Neurosurgery at the University of Colorado Denver. "Clearly, not all human astrocytes are equal when it comes to promoting repair of the injured central nervous system."

The research teams from Rochester and Denver also found that transplanting the original stem cells directly into spinal cord injured rats did not aid recovery. Researchers believe this approach - transplanting undifferentiated stem cells into the damaged area and hoping the injury will cause the stem cells to turn into the most useful cell types - is probably not the best strategy for injury repair.

According to Mark Noble, director of the University of Rochester Stem Cell and Regenerative Medicine Institute, "This study is a critical step toward the development of improved therapies for spinal cord injury, both in providing very effective human astrocytes and in demonstrating that it is essential to first create the most beneficial cell type in tissue culture before transplantation. It is clear that we can not rely on the injured tissue to induce the most useful differentiation of these precursor cells."

To create the different types of astrocytes used in the experiment, researchers isolated human glial precursor cells, first identified by Margot Mayer-Proschel, Ph.D., associate professor of Genetics at the University of Rochester Medical Center, and exposed these precursor cells to two different signaling molecules used to instruct different astrocytic cell fate - BMP (bone morphogenetic protein) or CNTF (ciliary neurotrophic factor) .

Transplantation of the BMP human astrocytes provided extensive benefit, including up to a 70% increase in protection of injured spinal cord neurons, support for nerve fiber growth and recovery of locomotor function, as measured by a rat's ability to cross a ladder-like track.

In contrast, transplantation of the CNTF astrocytes, or of the stem cells themselves, failed to provide these benefits.

Researchers are currently investigating why one type of astrocytes performed so much better than the other; however, it is likely that multiple complex cellular mechanisms are involved.

"It is estimated that astrocytes make up the vast majority of all cell types in the human brain and spinal cord, and provide multiple different types of support to neurons and other cells of the central nervous system," said Jeannette Davies, Ph.D., assistant professor at the University of Colorado Denver and co-lead author of the study. "These multiple functions are likely to all be contributing to the ability of the right human astrocytes to repair the injured spinal cord."

With these results, the Proschel and Davies teams are moving forward on the necessary next steps before they can implement the approach in humans, including testing the transplanted human astrocytes in different injury models that resemble severe, complex human spinal cord injuries at early and late stages after injury.

"Studies like this one bring increasing hope for our patients with spinal cord injuries," said Jason Huang, M.D., associate professor of Neurosurgery at the Medical Center and Chief of Neurosurgery at Highland Hospital. "Treating spinal cord injuries will require a multi-disciplinary approach, but this study is a promising one showing the importance of modifying human astrocytes prior to transplantation and has significant clinical implications."

In addition to Proschel and Noble, Davies and Davies, Margot Mayer-Proschel, Ph.D., and Chung-Hsuan Shih, from the University of Rochester Medical Center contributed to the research. Portions of this research were funded by the New York State Spinal Cord Injury Research Program, the Carlson Stem Cell Fund and private donations by the international spinal cord injury community.

Funding: This work was supported by funding from the National Institutes of Health [grant numbers RO1-NS046442, RO1-NS42820]; and the CareCure SCI community. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation:

"Transplantation of Specific Human Astrocytes Promotes Functional Recovery after Spinal Cord Injury."
Davies SJA, Shih C-H, Noble M, Mayer-Proschel M, Davies JE, et al. (2011)
PLoS ONE 6(3): e17328. doi:10.1371/journal.pone.0017328

Heart disease is linked to just a few rogue genes as well as lifestyle choices, landmark research into Britain's biggest killer has found.

The 18 genes that raise the risk of cardiac problems, from heart attacks to hardening of the arteries, have been pinpointed in three studies involving hundreds of scientists worldwide.

The breakthrough opens the door to ways of treating and even preventing heart disease, which is to blame for one in eight deaths around the world - including more than 90,000 a year in the UK.

Heart attacks alone kill one Briton every six minutes and cost the economy euro 9billion a year.

The potential of the findings is so great that heart disease could be eradicated within 50 years, say researchers.

The discovery, detailed in the journal Nature Genetics, more than doubles the number of known heart disease genes.

Some of the newly discovered genes affect cholesterol, blood pressure and other processes important to heart health - but how many of the others damage the heart and arteries is, as yet, a mystery.


This has excited the scientists because it suggests there are important causes of heart disease yet to be found - and that drugs to combat the effects of the genes could one day make a huge improvement to health.

Dr Robert Roberts, of the University of Ottawa Heart Institute, Canada, said: 'This is a landmark result because we have identified so many genes and most operate using completely unknown mechanisms to us right now. Now our job is to understand how these genes work, develop a new group of drugs to target them and identify people who will benefit most.'

Professor Nilesh Samani, of the University of Leicester, who co-led the largest of the studies, said: 'Understanding how these genes work, which is the next step, will vastly improve our knowledge of how the disease develops, and could lead to new treatments.'

The 18 genes were discovered in three studies in which almost 300 scientists from around the world, including many Britons, analysed the DNA of more than 200,000 people.

They focused on genetic links to the narrowing of the arteries that supply the heart muscle with oxygen-rich blood. This narrowing, caused by the build up of fatty deposits or plaques, raises the odds of a host of ills, from blood clots to angina, heart attacks, heart failure and irregular heartbeats.

Dr Thomas Quertermous, of Stanford University, in the U.S., said that drugs tailored to stop the blood vessels from becoming clogged up could 'profoundly reduce the risk of a heart attack'.

Professor Hugh Watkins, of Oxford University, who co-led one of the studies, said the first new drugs could be on the market in under a decade.

Some of the North American researchers said the breakthrough meant we were 'inching closer' to a genetic test that will tell a person their risk of a heart attack.

However, for most people, other factors such as smoking, poor diet and a lack of exercise can play a much greater role in causing heart attacks.

The country is being wrongly projected as a guinea pig for human clinical trials in the medical field but on the contrary, we are behind other countries in this regard, said Surinder Singh, Drugs Controller General of India.

"Around 1 lakh human clinical trials happen all over the world in a year. Among these, 52,000 trials happen in USA alone. Even Canada is home to large number of such trials whereas only 1.2% of these trial take place in India," he informed.

Singh was the chief guest at a national seminar on 'Regulatory Challenges- Global Pharmaceutical Market', organised by the Indian Pharmaceutical Association on Saturday in the city.

Singh said that a website will be launched soon which would make clinical trials a transparent procedure as it would contain all the previous and present information of the trials and the companies involved in it.

Accepting the fact that there were flaws in the system with respect to regulation of drugs, he said the government was working towards strengthening it. "We are short of manpower or infrastructure in regulating or controlling drugs. Hence the efforts are on to strengthen the state and central drugs control departments," he said and added: "300-400 crores have been released for the state drugs departments." He also said that a significant number of drug inspectors and laboratory specialists are being employed in the state and central drug departments along with the constitution of a new task force.

Singh expressed concerns over the presence of spurious drugs which were affecting the nation.

"We have been getting many letters from the Indian embassies abroad on the spurious drugs imports and its quality. This is bringing a bad reputation to the country." He also informed that UID bar codes will be made compulsory for all medicines soon to authenticate their quality. Also, he said, that there was a proposal to start auditing the foreign pharmaceutical companies which import their medicines into the country.

Speaking on the occasion, RP Meena, director general of Drugs and Copyrights, Andhra Pradesh appealed to the pharmaceutical companies to set up their manufacturing units in the backward areas of the state.

"Many pharma companies are moving to the himalayan states like Himachal pradesh, Uttarakhand and Jammu and Kashmir to set up their plants.

But they should concentrate on setting them up in the backward areas of AP too as this would provide employment to about 60% of the local population," he said.

Delivering the key note address, K Anji Reddy, chairman, Reddy's laboratories felt that there should be more focus on the availability and awareness of generic medicines as it would be helpful in providing cost effective treatment for the common man.

The Translational Health Sciences and Technology Institute (THSTI), an autonomous institute of the Government's Department of Biotechnology, and the International AIDS Vaccine Initiative (IAVI) has jointly announced an agreement to operate and fund an HIV vaccine design program in India.

The program, which will cost Rs. 50 crore over five years, will include the establishment of a new laboratory in THSTI campus in New Delhi.

The program will primarily focus on one of the greatest scientific challenges of AIDS vaccine design and development: the elicitation of antibodies capable of neutralizing a broad spectrum of circulating HIV variants, a problem that stems in large part from the almost unparalleled mutability of HIV.

"With 7,100 people newly infected with HIV every day, effective tools to prevent infection are indispensable to the fight against HIV and AIDS," said M.K. Bhan, Secretary of the Department of Biotechnology.

Meanwhile, under the banner of the Indian Drug Users Forum (IDUF), patients who have tested positive for HIV gathered here to opposed the Free Trade Agreement (FTA) with European Union that restricts them access to affordable medicines.

Presenting the painful scenario of their lives, IDUF activist Abou Mere said that the government provides drugs free of cost and if drugs are patented and come under FTA, the prices would increase.

"Government is providing drug free of cost, but if this patent takes place then the cost will go up. But what I am trying to highlight over here is Hepatitis C treatment has been patented and out of hundred, more than 90 percent people are affected and we, people who use drugs are not in a position to afford these drugs," said Abou Mere.

"It may be ex-users or current users, we are not in a position to afford these drugs and many people are dying. Therefore, the platform of Indian drug users has come out to against this free trade agreement," he added.

Abou Mere further informed that maximum people, who have tested positive for HIV, are poor, and the government must reconsider the decision to concur to the FTA.

Rajiv Kafle, a member of the Asia Pacific Network of the HIV-Positive People, said that these drugs are the lifelines of the HIV affected persons and if Government yields to the European Union's dictum, it would spell doomsday for the patients.

"We are here asking for our lives. These drugs mean they are our lifelines. And in the past when we didn't not have access to antiretroviral drugs, I have seen a lot of deaths due to HIV. We used to think that only rich people deserve to live and the poor people will deserve to die because of the cost involved in the drugs," Kafle added. (ANI)

A Wayne State University School of Medicine researcher has developed a personalized therapy that will fool cancer cells into killing themselves.

Developed by Karli Rosner, assistant professor and director of Research in the Department of Dermatology, the treatment uses genetic constructs that contain a genetically modified enzyme to seek out and destroy cancer cells.

The unique concept, patented by the university, was successfully demonstrated on melanoma cells that are resistant to routine treatments such as chemotherapy or radiotherapy.

The success of the therapy in killing melanoma suggests a similar outcome in treating other cancers.

Rosner modified the genetic code for DNase1, a highly potent DNA-degrading enzyme, and altered its genetic composition by deleting a part of the code, mutating another part and adding an artificial piece of code.

Through these changes, the altered DNA program is translated into a modified protein. In contrast to the natural protein, the modified protein will not be eliminated from the cancer cell, will resist deactivation by cell inhibitors and will gain access to the cell's nucleus. he cancer cell, unaware of the destructive potential of the modified code, translates it into a protein that evades the cell's defence mechanisms and enters the nucleus.

Accepting imperfections first step toward better health
In the nucleus, the protein damages DNA by chopping it into fragments without the need for other medications.

Following damage to DNA, the cell's organelles disintegrate and the cancer cell dies.

This mode of cancer cell elimination leaves no residual debris to alert the immune system to kick in, essentially committing 'the perfect crime', said Rosner.

This is important because the many side effects of current anti-cancer treatments are attributed to activation of the immune system.

The fact that this therapy does not require participation of the patient's immune system to kill cancer cells is a big advantage over other newly developed technologies, such as the cancer vaccine.

Patients with the same cancer type vary in their response to identical treatment because the biological characteristics of the same cancer type usually differ between patients.

As a result, the medical field strives to develop treatments that can be adjusted to each patient.

Customized health messages help quit smoking in 4 months

The structure of Rosner's technology contains Lego-like pieces that together form a genetic construct.

Each piece can be replaced by one of several other genetic pieces that perform the same task, but differ slightly in their genetics.

The multiple options available for each genetic piece will allow the physician to tailor the finalized treatment to each patient based on the unique characteristics of his or her cancer.

In this way, the new technology is a 'true personalized therapy', according to Rosner.