Report id’s medico-ethical issues restrict gene therapy growth

Increasing knowledge about how to manage the risks of gene therapy is set to usher in a new era in disease therapies, with the prospect of developing treatments in treating rare, inherited, or life-threatening diseases very real. Gene therapy has gone to great pains to deal with the toxicological complications and poor therapy efficacy that have hampered the growth of this sector.

So much so that the US gene therapies market, reveals that revenues expect to reach approximately $125 million (€106 million) in 2006 growing to approximately $6541 million in 2011.

This is not to say that gene therapy has not seen its fair share of clinical failures. Poorly regulated trials, and high levels of clinical attrition have seen the promise of gene therapy suffer from negative coverage and unsubstantiated claims.

Despite these remarkable strides, the fact remains that most biotech companies are still years away from having an approved and marketed product.

The only exception to this is the China-based company Shenzhen SiBiono GeneTech, whose product Gendicine, made news in October 2003 by becoming the first gene therapy in the world approved for marketing.

The treatment consists of an adenovirus designed to insert a gene called p53. This gene codes for a protein that triggers cell suicide when cells start to run amok, preventing them becoming cancerous.

Many tumours arise after the mutation or inactivation of p53, and in cancers of this type restoring the protein should kill the tumour cells.

The approval signals a breakthrough in the treatment of head and neck squamous cell carcinoma (HNSCC), while ongoing clinical trials expect to uncover more target cancer indications for Gendicine.

China's progress in the cell therapy market has not gone unnoticed by the west, in particular the United States. However, one could argue that US legislation and ethical wrangling concerning stem cells, a crucial factor in cell treatment, has slowed down progress, losing significant ground over rival countries.

"This is critical not only for treating the disease indication and offering hope to patients, but also to validate the whole gene therapy sector to the market and investors," said Raghunath Tantry, Frost & Sullivan's research analyst

"Companies such as Introgen Therapeutics have potentially successful late-stage pipeline products and this will add to the market momentum and increase the credibility of the technology," he added.

Introgen's INGN 241 (breast cancer) is in Phase 1-2 clinical development as is INGN 225 (lung cancer), a therapeutic vaccine, is in Phase 1-2 clinical development.

Also in Phase 1-2 clinical development are INGN 234 (a topical formulation for oral cancer prevention and treatment of oral pre-malignancies), a topical formulation for oral cancer prevention and treatment of oral pre-malignancies and INGN 401 a systemic nanoparticle tumour suppressor.

It seems that pressing concerns such as the medico-ethical issues is likely to have more of an impact on the market's fortunes than any health and safety concerns. Monitoring agencies have even questioned the ethics of testing these therapies on humans, since the science of genetics is still at a nascent stage of development.

"Successes, even minor safety and efficacy milestones, must be communicated to overcome the unwanted publicity received for toxicity and fatalities," commented Tantry.

"The market must be educated on the subtle ways to evaluate a gene therapy product for its benefits to patients that need those therapies."

By Wai Lang Chu

source: drugresearch

Earliest Animals Had Human-like Genes

image source: http://www.hhmi.org/annual96/research/pix/chart.gif

Species evolve at very different rates, and the evolutionary line that produced humans seems to be among the slowest. The result, according to a new study by scientists at the European Molecular Biology Laboratory [EMBL], is that our species has retained characteristics of a very ancient ancestor that have been lost in more quickly-evolving animals. This overturns a commonly-held view of the nature of genes in the first animals. The work appears in the current issue of the journal Science.

Genes hold the recipes for proteins. The genes of animals usually contain extra bits of DNA sequence, called introns - information which has to be removed as cells create new molecules. The number of introns in genes, however, varies greatly among animals. While humans have many introns in their genes, common animal models such as flies have fewer. From an evolutionary perspective, it was long assumed that the simpler fly genes would be more ancient. The current study reveals the opposite: early animals already had a lot of introns, and quickly-evolving species like insects have lost most of them.

To discover what early animals were like, scientists usually compare their descendents. This is difficult when comparing distantly-related animals such as humans and flies. In these cases, it helps to look at living organisms that have preserved many features of their ancestors. Detlev Arendt's group is doing this with a small marine worm called Platynereis dumerlii. "Similar animals are already found in the earliest fossils from the Cambrium, about 600 million years ago," Arendt explains, "arguing that Platynereis could be something like a 'living fossil'." This makes it an ideal model for evolutionary comparisons to find out what the common ancestors of humans, flies and worms were like."

Until quite recently, such comparisons could only be made by looking at physical characteristics such as the structure of bones, teeth, or tissues. But DNA sequencing now permits scientists to make comparisons of the genetic code and read evolutionary history from it. An international consortium involving researchers from EMBL, the UK, France and the United States has now sequenced a part of the Platynereis genome. "The fraction of Platynereis genes we have been able to look at tells a very clear story," says researcher Florian Raible, who performed most of the computer analyses. "The worm's genes are very similar to human genes. That's a much different picture than we've seen from the quickly-evolving species that have been studied so far."



Raible is member of both Arendt's group and a second EMBL lab, that of Peer Bork, whose specialty is analyzing genomes by computer. "Human genes are typically more complex than those of flies," explains Bork. "Classicallystudied species like flies have far fewer introns, so many scientists have believed that genes have become more complex over the course of evolution. There have already been speculations that this may not be true, but proof was missing. Now we have direct evidence that genes were already quite complex in the first animals, and many invertebrates have reduced part of this complexity."

Not only are the introns there - the team also discovered that their positions within genes have been preserved over the last half a billion years." This gives us two independent measurements that tell the same story," Raible explains. "Most introns are very old, and they haven't changed very much in slowly-evolving branches of life, such as vertebrates or annelid worms. This makes vertebrates into something like 'living fossils' in their own right."

The discovery that Platynereis also represents a slowlyevolving branch of animal life has important implications for the study of humans. "We've already learned an incredible amount about humans from studies of the fly," Arendt says. "The marine worm might well give us an even better look at important conserved processes. Another thing that this has shown us is that evolution is not always about gain; the loss of complexity can equally be an important player in evolution."

Source article:

Vertebrate-type intron-rich genes in the marine annelid Platynereis dumerilii
F. Raible, K. Tessmar-Raible, K. Osoegawa, P. Wincker, C. Jubin, G. Balavoine, D. Ferrier, V. Benes, P. de Jong, J. Weissenbach, P. Bork and D. Arendt.
Science, 25 November 2005

The original news release can be found here.

Clone human embryo creator admits ethical lapses in work

Alok Jha, science correspondent Friday November 25, 2005 The scientist who created the first clone human embryo was forced to apologise yesterday for ethical lapses in his work. Professor Woo-Suk Hwang of Seoul National University said some of the eggs used in his experiments to create human clones were donated by two junior members of his research team. He admitted his focus on the research had led him to overlook the related ethical issues.

An investigation by the South Korean health ministry also found some women were paid for their eggs, a practice that is now illegal in the country. "I am very sorry that I have to tell the public words that are too shameful and horrible," said Prof Hwang at a news conference yesterday. "I should be here reporting the successful results of our research, but I'm sorry instead to have to apologise."

Prof Hwang said he would resign as the head of the World Stem Cell Hub in a bid to "atone to the public". The hub, launched in Seoul last month, aims to help coordinate global efforts to use stem cells in the search for treatments for incurable diseases such as Alzheimer's and Parkinson's. The group had announced plans to open laboratories in San Francisco and England, but Prof Hwang's close collaborators, including University of Pittsburgh researcher Gerald Schatten, dropped out of the project following the allegations of unethical egg collection.

A hero in his native South Korea, Prof Hwang made headlines last year when he announced he had extracted stem cells, the master cells that can turn into any type of cell, from the first cloned human embryo. Earlier this year he unveiled Snuppy, the world's first cloned dog.

Reports that Prof Hwang may have used eggs from members of his research team first appeared in the scientific journal Nature last year. Prof Hwang said this was the first time the issue had been brought to his attention and that when he asked the scientist in his team, she admitted donating eggs but asked for her privacy to be maintained.

Prof Hwang said: "I have learned a painful lesson that I should conduct research in a calm and cautious manner by living up to a global standard."

But Prof Hwang's Seoul team are unfazed by the revelations. Lee Jeong-Ryul, a cardiac surgeon, said the dispute was "no reason to stop stem cell research".

source: The Guardian

Hair follicle stem cells repair nerve damage: study

Los Angeles | November 23, 2005 11:15:06 AM IST Patients with an injured nervous system could be cured with their own hair follicle in future, as US and Japanese scientists have succeeded in curing severe nerve damage in mice by using tissues differentiated from hair follicle stem cells.

The results of the new research suggest hair follicle stem cells can promote nervous axon growth and functional recovery after nerve injury, thus offering an opportunity for the clinical treatment of peripheral nerve diseases, said the researchers.

The team, including researchers from the Massachusetts Institute of Technology, the Kitasato University of Japan, and the University of California, San Diego, reported this achievement in the latest issue of the journal the Proceedings of the National Academy of Sciences.

Embryonic stem cells, known to be capable of differentiating into almost all tissue cells, have aroused ethical debates in many countries. Scientists also found that problems such as immunologic incompatibility are linked with embryonic stem cells.

Therefore, more recent studies have focused on adult stem cells for future clinical applications. And hair follicles afford a highly promising source of relatively abundant and accessible, active, pluripotent adult stem cells, said the researchers.

In earlier studies, the team led by Robert Hoffman, a professor at the University of California, San Diego, has induced hair follicle stem cells to differentiate into blood vessel cells and neurons. The researchers said these studies suggested the potential of hair follicle stem cells to form diverse cell types.

Now the researchers have successfully coaxed the hair follicle stem cells to evolve into the Shwann cells, a variety of glia cells that wrap around axons in the peripheral nervous system.

When injected into disabled mice with injured sciatic nerve, these Shwann cells produced myelin sheaths that surround nerve axons, and then the mice were able to walk normally, the researchers reported.

"Therefore, by differentiating into Schwann cells, the hair follicle stem cells may stimulate the host axons to extend and, thus, to fill the transaction gap," they said in the paper.

Hair follicle stem cells may be more promising in therapies, according to the researchers. In the future, patients with injured nervous system could be cured with their own hair follicle.

--Xinhua



(IANS)

Vietnamese scientists decode gene of bird flu virus

H5N1 Virus

Vietnamese scientists have decoded the gene of H5N1 virus, paving the way for defining the variations and transmission mechanism of the bird flu virus, local newspaper Youth reported Wednesday. Vietnam's Ho Chi Minh City Pasteur Institute and the Regional Veterinary Centre in the southern city claimed Tuesday they have entirely decoded the gene of the virus.

Ngo Bao Long, of the Veterinary Centre, said they found not only the virus strain H5, but also two other strains of H3 and H4 in two samples from poultry.

Theoretically, when a fowl is infected with H5, H3 and H4 at the same time, the viruses can swap their genes to create a new virus strain, which can be more dangerous, he said.

Vietnam, in early 2006, is likely to churn out 20-50 million dozes of H5N1 vaccines to be used for poultry next year, said the biotechnology institute's director Le Tran Binh, adding his institute has completed procedures to produce the vaccines.

Meanwhile, the country's National Institute of Hygiene and Epidemiology is completing final procedures to produce H5N1 vaccines to be used for people. The Hanoi-based institute that has been involved in research into the vaccines since 2004, has proposed the health ministry use them on trial basis in early 2006.

Since December 2004, Vietnam has detected 65 human cases of bird flu infections, including 22 fatalities, according to the health ministry.

--Xinhua

source: (IANS)

Heart risk gene hits African Americans hardest

A gene commonly found in Americans of European descent can be deadly when carried by African Americans, a new study has revealed. The gene variant more than triples the risk heart attack in African American populations, the researchers found. African Americans are known to be more prone to heart attacks and the researchers suggest this may partly be due to European ancestry in those individuals, although environmental factors are certainly involved.

Kári Stefansson at Decode Genetics in Reykjavik, Iceland, and colleagues, isolated a gene variant called HapK, which is found in 30% of European Americans and 6% of African Americans. The variant also occurs in about 35% of people in Asia, but native Africans do not possess the gene. Stefansson proposes that the gene mutation must have occurred after the migration of human populations from Africa, about 50,000 years ago.

HapK is involved in series of biochemical steps that leads to inflammation in the body. Its role is not fully understood but it is believed to increase the propensity of fatty deposits in the arteries – atherosclerotic plaques – to rupture, leading to a heart attack.

250% increased risk
Stefansson studied the significance of the gene variant in more than 3000 people in three groups, one at the Cleveland Clinic in Ohio, one at Emory University in Atlanta, and one at the University of Pennsylvania in Philadelphia, all in the US.

In the study, published in Nature Genetics, they found that HapK was associated with a slight increase in risk of heart attack for participants of European descent – just 16% – while those of African descent were 3.5 times more likely to suffer a heart attack (equivalent to a 250% increase in risk).

“If you’re an African American with the variant gene you are close to certain to have a heart attack if nothing is done about it,”"It’s very important to screen and find this subgroup,” Stefansson says. His biopharmaceutical company has two potential drug therapies in clinical trials which act by regulating the inflammatory pathway that HapK is involved in.

Micro-flora defence
Martin Godfrey, a physician at the British Cardiac Society, notes: “There are significant ethnic variations in heart attack risk. Black people in Britain and America are particularly at risk and they have increased incidence of strokes and high blood pressure.”

Stefansson speculates that the variant is so dangerous in African Americans because, unlike European Americans, they have not had thousands of years to adjust to its presence in their genome.

“The inflammatory pathway probably developed as a protective response to micro-organisms; and as populations inhabited very different areas, the micro-flora they encountered was vastly different,” he says. “That may be the reason for the differences in frequency of the variant.”

Journal reference: Nature Genetics

source: morover

Some 32,000 genes to go in squid research project

WOODS HOLE, Massachusetts The room is filled with marine life: fiddler crabs and moon snails, dogfish and flounder. There are clams stacked up by the dozen, with signs that require second looks. "Toadfish infected with lice," one sign says. "Do not touch." But Joe DeGiorgis, 41, walks right past it all. He has come to the Marine Resource Center in Woods Hole for one thing and one thing only. "The squid are here," he calls out, pointing to a large oval tank. "My favorite guys." DeGiorgis, smiling, peers inside the tank. It's filled with dozens of long-finned Atlantic squid - 12 to 18 inches in length, or about 30 to 46 centimeters long, typical in every way as far as squid are concerned. DeGiorgis likes fried calamari as much as the next guy. But as a post-doctoral fellow at the National Institutes of Health who spends half the year working at the Marine Biological Laboratory in Woods Hole, he has other reasons for admiring these mollusks.

He and a colleague, J. Peter Burbach, a professor of molecular neuroscience at University Medical Center Utrecht in the Netherlands, are the minds behind the Squid Genome Project, a surprisingly successful attempt to map the squid's genetic thumbprint in the hopes that its secrets may help solve mysteries like Alzheimer's disease.

On a budget of roughly $100,000, DeGiorgis and Burbach have identified more than 3,000 of the squid's estimated 35,000 genes, including, DeGiorgis said, the gene that causes the body to produce insulin, and genes linked to

Alzheimer's and a degenerative and fatal neurological disease called Niemann-Pick Type C in humans.

That's no small accomplishment. Stephen Sturley, an assistant professor of pediatrics at Columbia University, said DeGiorgis's work may one day help doctors find a cure for Niemann-Pick. And that, says DeGiorgis, is only the beginning.

"If the project were to stop today," he says, "I've got enough genes to work on for the rest of my career."

DeGiorgis grew up on Jacques Cousteau television shows and took up scuba diving in high school. He got his first job at the Marine Biological Laboratory in Woods Hole before his senior year in college.

It wasn't much, just a diving job. DeGiorgis dove for surf clams in the sandbars off Martha's Vineyard and brought them back to Woods Hole for scientists to study. He came to learn that the scientists were interested in what marine life, namely clams and squid, could reveal about people.

Squid, he learned, are especially powerful models. Their giant axon, a channel of nerve fibers in their back, is 1,000 times wider than the average human axon - an easy target for researchers who want to study how information travels and systems break down. DeGiorgis set up a private company to do dissections of the axon and other oddities. For a time in Woods Hole, he was the guy you called when you needed, say, 2,000 squid eyes, dissected and ready to be studied.

As DeGiorgis got his doctorate in cell and molecular biology from Brown University in 2001, he began to focus on mapping the squid genome.


"Some people were like: 'What would you do with it if you had it?' They didn't understand the significance of the work," he says. But DeGiorgis knew the squid could provide insight into the human condition.

DeGiorgis peers down at the squid in the water. He nets one, and it promptly sprays him in the face with black ink. DeGiorgis smiles.

Squid, he says, are beautiful.

source: IHT