Children’s Hospital on cusp of gene therapy breakthrough

June 27, 2010

Children’s Hospital on cusp of gene therapy breakthrough

Local researchers are awaiting the green light to test a cutting-edge cure for a devastating disease that leaves babies unable to fight off the simplest infections.

Cincinnati Children’s Hospital Medical Center has gotten permission from the U.S. Food and Drug Administration to test a gene therapy treatment against X-linked severe combined immunodeficiency, or so-called “bubble-boy” disease. It’s the first federal approval the Corryville hospital has received for a gene therapy treatment conceived and manufactured in its own lab.

Now, Alexandra Filipovich and her colleagues are waiting for the hospital’s own institutional review board to sign off the trial.

“We’re ready to go,” said Filipovich, director of the hospital’s immunodeficiency and histiocytosis program and the primary investigator for the trial.

Maverick Steiner was only 4 months old when he was diagnosed with the disease after a long run of illnesses, including ear infections and diarrhea that wouldn’t go away. Doctors grew worried when he developed a form of pneumonia normally seen in AIDS patients – a sign his immune system was seriously compromised.

The immune disorder is caused by a defective gene that leaves babies unable to make two types of cells that attack bacteria, viruses and certain cancers.

For most babies, including Maverick, a bone marrow transplant cures the disease. But 20 to 30 percent of babies born with the disorder can’t get a transplant. Either they can’t find a donor match or they’re too sick to withstand the procedure.

For those babies, gene therapy could be the answer. It relies on technology that lets doctors custom-tailor viruses that, instead of causing sickness, cure it.

For Filipovich’s experiment, researchers will collect stem cells from babies with the immune disorder.

In the lab, those stem cells will be infected with specially designed viruses that carry a functioning copy of the defective gene that causes the immune disorder. The viruses have been engineered so that they can’t cause illness.

Doctors then will put the stem cells with the functioning gene back in the babies through an IV. If the experiment works, the new gene will let the babies’ immune systems function normally, and they’ll be able to fight off infections.

The viruses carrying the new gene were designed and built at Cincinnati Children’s.

The idea of using viruses to attack disease has great potential for treating cystic fibrosis, Huntington’s disease, sickle cell anemia and some forms of cancer, including brain tumors, said Han van der Loo, the lab’s director. It also has the potential to attract world-class researchers, coveted federal research dollars and private pharmaceutical contracts.

Dr. Punam Malik, a hematology-oncology expert and co-director of the lab, came to Cincinnati because of the viral vector lab.

Malik, now the lab’s co-director, is heading up a clinical trial testing gene therapy as a potential cure for sickle-cell anemia. The trial could start in the spring of 2011.

Malik is organizing a clinical trial to test gene therapy as a potential cure for sickle cell anemia. She’s still waiting for approval from federal regulators.

It’s taken Malik and her colleagues 10 years to get to this point – and the therapy hasn’t been injected into a human being yet. It has been tested in lab animals, but the altered viruses had to be designed and manufactured, and that process costs money.

Without the in-house lab, Malik said, she and her colleagues would have had to contract with another research-grade lab, which would have required them to put the science on hold while they found money. “We can’t afford to do that,” she said.

To produce the altered viruses in both the quantity and quality suitable for use in humans, Malik and other researchers without access to an in-house lab would likely need to turn to the pharmaceutical industry. But the industry isn’t likely to be interested in producing an extremely expensive drug that might not work.

“They don’t want to take a risk. They want a return on investment, and we have no idea if we will have a return on investment,” she said.

Because Cincinnati Children’s has its own viral vector lab and its own lab for processing pharmaceutical-quality stem cells, the pressure to make a profit is off. Researchers like Malik just have to find enough money to cover the cost of labor and materials.

The viral vector lab, a 10,000-square foot facility with nine “clean rooms” in which technologists make the altered viruses, has the capacity to make a gene therapy drug in sufficient quantities for small-scale human testing. Filipovich hopes to recruit three patients through the hospital for the first phase of her immune disorder experiment.

If a gene therapy drug were found to be safe and effective enough to go onto large-scale trials – meaning it was likely to win FDA approval and make it to the market – the hospital would likely license, or sell, the drug to a pharmaceutical company.

Such a sale, which could mean millions of dollars.

The hospital is already expecting other kinds.

Because of the XSCID trial, Filipovich and her colleagues are getting invitations from researchers in Europe to participate in a number of projects. There’s no way to put a price tag on that kind of opportunity, she said.

For parents, there’s no way to put a price tag on their children’s health.

Maverick, now 16 months old, is doing well since the bone marrow transplant, said his mother, Jessica Steiner. She and her husband, Ryan, live in St. Bernard.

But Maverick spent nearly four months in the hospital while he was waiting for the bone marrow transplant, which he underwent in October.

“He’s doing great now,” she said.

CORRECTION: An earlier version of this story incorrectly spelled the name of Dr. Punam Malik

linkback url:


WI Public Health Lab Identifies First SCID Baby Using New TREC Assay

June 16, 2010

Michelle M. Forman, Senior Media Specialist
For Immediate Release
June 16, 2010
WI Public Health Lab Identifies First SCID Baby Using New TREC Assay
Silver Spring, MD–The Wisconsin State Laboratory of Hygiene at the University of Wisconsin-Madison has identified the first baby with classical Severe Combine Immune Deficiency (SCID) as part of their newborn screening program. SCID babies, if undiagnosed, eventually develop severe life-threatening infections with a 100% mortality rate, usually within the first year of life. With prompt diagnosis and treatment before the infections, SCID is curable when treated by hematopoietic stem cell transplantation (HSCT). This is the first and only condition on the newborn screening panel of 30 genetic diseases that is curable if diagnosed very early in an infant’s life. SCID refers to a collection of inherited immunodeficiencies characterized by profound defects of both T cell and B cell arms of the immune system.
According to Dr. Christine M. Seroogy, associate professor in the Department of Pediatrics at the University of Wisconsin, “The ability to cure validates why we do this test. It is working the way it was designed to work.”
In an extraordinary collaborative effort in 2007, Dr. Mei Baker, science director of the Wisconsin State Laboratory of Hygiene’s Newborn Screening Program, worked closely with Drs. John Routes and William Grossman, both with the Children’s Hospital of Wisconsin and Medical College of Wisconsin, to develop a molecular assay that detects the absence of TRECs (T cell Receptor Excision Circles) using dried bloodspots and determined that it was the most effective way to diagnose SCID. TRECs are small pieces of DNA generated in T cells as they mature.
“This is the first time a molecular assay is being used as a primary screening test in newborn screening,” says Dr. Baker, who is also an assistant professor of pediatrics at the University of Wisconsin. “The SCID test is a perfect example of applying advanced molecular knowledge and technology in public health newborn screening programs.”
Dr. John M. Routes, medical director, section of allergy and immunology, Children’s Hospital of Wisconsin feels that newborn screening for SCID has already been a tremendous success. “In 2007 we determined that it was feasible to conduct high throughput TREC assays for SCID screening within a public health laboratory and now it
is happening and has already saved a baby’s life.” Dr. Routes was responsible for securing initial funding for the project, a $250,000 grant from the Jeffrey Modell Foundation and a $250,000 grant from the Children’s Hospital of Wisconsin.
Since then, a grant from the Centers for Disease Control and Prevention (CDC) has allowed the program to continue. Part of the grant from CDC was to be used to train laboratories in other states to perform the TREC assay. The Wisconsin State Laboratory of Hygiene as well as the New England Newborn Screening Program in Massachusetts have been in contact with at least 10 other state laboratories interested in adding the TREC assay and SCID to their screening panel. Wisconsin will begin working with Louisiana to initiate screening for SCID sometimes after July 1, 2010. Currently, Wisconsin and Massachusetts are the only two states that screen for SCID.
“State public health laboratories and newborn screening lead the way in identifying infants with life threatening conditions. This has always been part of our public health mission, and we believe that there will be additional opportunities to expand newborn screening as a result of the work here in Wisconsin,” says Dr. Charles D. Brokopp, Director of the Wisconsin State Laboratory of Hygiene.
According to preliminary data from the Children’s Hospital of Wisconsin, a single baby with a late SCID diagnosis costs an average of $2.2 million. Medical care for one baby with an early SCID diagnosis costs $250,000. Testing the 70,000 babies born annually in Wisconsin for SCID as part of the routine newborn screening panel costs approximately $350,000 ($4-5 per test). According to Dr. Brokopp, “The savings from one positive diagnosis pays for testing of all babies for the entire year.”
The Wisconsin State Laboratory of Hygiene is a member of the Association of Public Health Laboratories (APHL). APHL’s Newborn Screening and Genetics Program works to strengthen the role of public health laboratories in genetic testing and designs strategies to address changes in the newborn screening testing field. The association collaborates with the Centers for Disease Control and Prevention to provide input on quality control and proficiency testing issues relevant to newborn screening laboratories across the globe.
The Association of Public Health Laboratories is a national non-profit located in Silver Spring, MD, that is dedicated to working with members to strengthen governmental laboratories with a public health mandate. By promoting effective programs and public policy, APHL strives to provide public health laboratories with the resources and infrastructure needed to protect the health of US residents and to prevent and control disease globally.

linkback url:
# # #

CDC: SCID is Contraindication for Rotavirus Vaccine

June 10, 2010

CDC: SCID is Contraindication for Rotavirus Vaccine

By Todd Neale, Staff Writer, MedPage Today
Published: June 10, 2010

ATLANTA — Rotavirus vaccine should not be given to infants with severe combined immunodeficiency (SCID), according to new CDC guidance.

The makers of the two live rotavirus vaccines — GlaxoSmithKline Biologicals (Rotarix) and Merck (RotaTeq) — had revised their labels in line with the change in December and February, respectively, with FDA approval.

The CDC announced the addition of severe combined immunodeficiency to the list of contraindications for the vaccines in the June 11 issue of Morbidity and Mortality Weekly Report, following consultations with members of the former Rotavirus Vaccine Work Group of the Advisory Committee on Immunization Practices (ACIP) and a review of the data.

Furthermore, “consultation with an immunologist or infectious disease specialist is advised for infants with known or suspected altered immunocompetence before rotavirus vaccine is administered,” the agency said.

Merck and GlaxoSmithKline Biologicals made the labeling changes in response to eight reports of vaccine-acquired rotavirus infection in infants with severe combined immunodeficiency since the 2006 approval of RotaTeq. Seven were related to the pentavalent RotaTeq and the last was related to the monovalent Rotarix, which was approved in 2008.

Five of the cases — four in the U.S. and one in Australia — were reported in the literature and another three — two in the U.S. and one from outside the U.S. — were reported to the Vaccine Adverse Event Reporting System.

All of the infants, who were diagnosed with severe combined immunodeficiency at between 3 and 9 months of age and had received at least one dose of the vaccine before diagnosis, had diarrhea from the rotavirus infection.

In all eight cases, vaccine-acquired rotavirus infection was confirmed by reverse-transcription-polymerase chain reaction and nucleotide sequencing.

Prolonged shedding of the virus was documented in at least six cases with a duration of up to 11 months.

For infants in whom it is not contraindicated, rotavirus vaccination is recommended by ACIP in three doses at ages 2, 4, and 6 months for RotaTeq and in two doses at ages 2 and 4 months for Rotarix.

linkback url:

125,000/1 against: this boy’s chances of finding a bone marrow donor…

June 8, 2010

125,000/1 against: this boy’s chances of finding a bone marrow donor…

..but were he white it would be a different story. Jerome Taylor reports on the racial lottery for patients in need of transplants

Tuesday, 8 June 2010

Ten-year-old amun Ali desperately needs a bone marrow transplant. If he were white, the likelihood of his finding a life-saving match would be one in three. But he is Asian so his chances are closer to one in 125,000.

The chronic shortage of ethnic minorities on Britain’s various donor registries – be they blood, bone marrow or hard organs – means that the chances of survival for thousands of patients like Amun are drastically reduced.

Patients from South Asian or black backgrounds are three times more likely to need a kidney transplant as white patients. But once they get on to the list they usually have to wait twice as long, which in turn increases the chances of the kidney being rejected because bodies that have had to spend long periods on dialysis often have a harder time accepting new organs.
The sad truth is that for children such as Amun, the road to recovery is fraught with added difficulties simply because of their race.

Things become even more complicated for people of mixed-race backgrounds, where the blending of Britain’s gene pool – considered by geneticists as something that will improve the overall health of our society – makes the search for a suitable transplant fiendishly complex.

Other than the liver, which is remarkably resilient, most donated organs need to come from donors that are both the same blood type and tissue type, otherwise the body’s immune system will kick in and reject the organ. We inherit blocks of tissue type from both our parents, which means mixed-race children often have much more complex or rarer tissue types than the national average.

“Mixed-race patients tend to have the hardest time looking for unrelated donors,” Professor Steven Marsh, the deputy director of research at the Anthony Nolan Trust, says. “If someone inherits a very common Chinese half of their tissue type from one parent and a very common British tissue type from another, then the only people who will really be matches for them are other mixed-race people with the same tissue types.”

This disparity has profound implications for the way we treat our children in the future and how we go about ensuring our donor databases reflect the ever-growing ethnic variety of the British public. A recent paper from the Institute for Social and Economic Research showed that nearly one in 10 British children is now born to mixed-race parents. Taken as a whole category, “mixed race” is now the fastest-growing ethnicity in the UK and yet it is the least represented on all our donor registers.

The Independent recently highlighted the case of Devan Tatlow, a mixed-race four-year-old boy in Washington, DC who is undergoing treatment for leukaemia and desperately needs a bone marrow transplant. His body contains a multitude of genes from his parents, who are of Irish and Indian-Polish descent. When doctors searched the global bone marrow database of 14 million donors they couldn’t find a single match. It took a mass campaign of emailing and pleading by friends, activists and celebrities alike before a potential match was found using cord blood, the stem cell-rich blood that remains in the umbilical cord at birth and is all too often thrown away. Devan’s journey towards full recovery will still be fraught with difficulties, but he has at least found a match.

Yet even when both sets of parents are from the same ethnicity, finding matches can be heartbreakingly difficult for black and ethnic minority (BME) families.

Amun loves wrestling and playing basketball. But for the past six weeks, his home has been a sterile ward at Birmingham’s Heartlands Hospital.

Amun was born with a severe immunodeficiency syndrome that leaves him painfully vulnerable to infections, and in the past few months his condition has deteriorated.

His only chance of long-term survival is a full bone marrow transplant which doctors hope will stimulate his body into creating enough white blood cells to fight off infections.

When his family were told that none of his relatives was a suitable match, they instantly feared the worst.

“We had already lost Amun’s younger brother Ali to the same disease,” said his father, Ashgar Khan, who has since given up his job to care full time for his son. “By the time we discovered his sister was a match it was too late. This time, none of us are matches for Amun.”

The Ali family is aware that the only way they will find a saviour for Amun is to galvanise more South Asians into signing up to the various registries in the hope that somewhere out there is a match. Helped by Desi Donors, one of the only charities working with South Asian donors, they have held a series of “clinics” in and around Birmingham encouraging community members to become donors.

“We haven’t found a match for Amun yet but both times we got about 70 people to sign up,” Mr Khan said. “That might not sound like a lot but in the Asian community it really is.”

Those working within Asian and some black cultures say organ-donating is still viewed with deep suspicion. Feelings tend to be more entrenched among older generations, where culture, customs and some religious communities remain vehemently opposed to the idea of meddling with the body before and, particularly, after death.

“Most of the time, I think it’s just accidental ignorance,” says Reena Combo, who co-founded Desi Donors after meeting Dean Sheikh, a seven-year-old who needed a bone marrow transplant but sadly passed away last year without finding a match. “If you don’t know about something you tend to turn a blind eye to it.”

Leila Molaei, who was involved in organising publicity for an NHS campaign earlier this year encouraging ethnic minorities to join donor registers, says religion is overly criticised for being the main stumbling block.

“It’s more to do with culture rather than religion,” she says. “People of Arab or Iranian descent, for instance, are more comfortable with the idea of becoming a donor than, say, Pakistanis. We tended to find that Hindus are the most relaxed about donorship, followed by Sikhs and then Muslims.”

Professor James Neuberger, the associate medical director for Organ Donation and Transplantation at NHS Blood and Transplant unit, says changing mindsets will not happen overnight. “It’s something we will have to continue working at from different angles over the coming years. But ultimately changing the culture will take a few decades before we start to see any major impact,” he says.

Why does race matter?

What makes a transplantation successful largely depends on whether the recipient’s body accepts the new organ. Those chances are massively increased if the donor has the closest tissue type as possible to the recipient. Race plays a crucial role in deciding our tissue type.

“The genes that are responsible for your tissue type are not there just to confound transplant surgeons,” explains Professor Steven Marsh. “They are there because they have a role in immunity. These genes are constantly changing and mutating. As man has moved around the world, these genes have changed to help us deal with the various pathogens we encounter. The bottom line is someone in China will have a very different tissue type from someone in northern Europe.”

If the tissue type of the donor is different from the recipient, the immune system of the transplant patient will attack the organ. Blood type also plays a crucial role. In Britain the most common blood types are O and A. In South Asia blood types B and A are far more common. Transplant patients with B-type blood in the UK statistically have a smaller chance of finding a suitable organ because their blood type is so much rarer within the wider population.

Religion: Faiths encourage the selfless act of organ donation

Faith leaders from minority religions have gone on the offensive in recent years encouraging devotees to register as organ donors.

Hindu and Sikh religious authorities have few problems with the process. Both view the body as a temporary vessel for the soul and emphasise the importance of selfless giving.

Islam has no qualms with live donorship, like when a parent donates a kidney to their child. But post-mortem organ donation is a little more complicated. Islam places immense importance on the treatment of a body with strict requirements designating how the dead should be washed and prepared for burial without interference. Cutting open bodies, even for autopsies, is sometimes frowned upon.

The majority of sharia schools, however, say organ donation is permissible because of the Islamic concept of al-darurat tubih al-mahzurat, the idea that the necessity of something sometimes outweighs its prohibition. The Koran says that saving one life is akin to saving the whole of mankind and the majority of jurists, including the Muslim Law (Shariah) Council UK, say organ donation is a selfless act that saves lives and should be encouraged. Other shariah schools, however, remain opposed, leading to much confusion.

Christianity emphasises selflessness and sacrifice for the greater good. Although there are no teachings against organ donorship, some church leaders in the developing world preach against it.

Transplants in numbers

1 in 3 The likelihood a white person can find a bone marrow match

1 in 125,000 The likelihood an Asian or Black person can find a bone marrow match

1 in 200,000+ The likelihood a mixed race person can find a bone marrow match

16.9m people on the NHS Organ Donor Register, but only 1.2 per cent of these are from the Asian community and 0.4 per cent of these from Black communities

7,800 patients are actively waiting for a transplant, of whom 1,521 are South Asians and 779 are Black

Between 1 April 2008 and 31 March 2009:

3,513 organ transplants were carried out, thanks to the generosity of 1,853 donors

977 lives were saved in the UK through a heart, lung, liver or combined heart/lungs, liver/kidney, liver/pancreas, heart/kidney or liver/kidney/pancreas transplant
Private Medical Cover from £30 per month with Independent Compare

linkback url:

Spain’s Grifols buys US biotech company Talecris

June 7, 2010

Spain’s Grifols buys US biotech company Talecris

MADRID — Spanish healthcare company Grifols SA said Monday it had acquired Talecris Biotherapeutics, based in North Carolina, for euro2.8 billion ($3.4 billion).

In a statement on both companies’ websites, Grifols, a leading producer of blood plasma products and therapies, said the deal would create “a global leader of lifesaving and life-enhancing plasma protein therapeutics.”

The company said the acquisition of Talecris is expected to generate approximately euro190 million ($230 million) in operating synergies.

The statement said the resulting transaction value of the deal, including net debt, would be approximately euro3.3 billion (US$4 billion).

The combined company will have pro-forma annual revenues of approximately euro2.34 billion ($2.8 billion), the statement said.

The Spanish company’s shares were down 6.5 percent at euro8.6 ($10.28) in afternoon trading in Madrid that saw most companies’ shares fall.

The statement said the leading shareholders of Grifols had agreed to vote in favor of the transaction and an affiliate of Cerberus Capital Management, L.P., which owns approximately 49 percent of the outstanding Talecris common stock, had entered a similar agreement.

The transaction is expected to close in the second half of 2010.

Grifols, with centers in more than 90 countries, researches, develops, manufactures and markets plasma derivatives, IV therapy, enteral nutrition, diagnostic systems and medical materials.

Talecris is a worldwide biotherapeutic and biotechnology company that discovers, develops and produces critical care treatments for people with life-threatening disorders, the statement added.

The company operates more than 50 plasma collection centers and two manufacturing plants in the United States.

linkback url:

%d bloggers like this: