Newborn screening test can detect life-threatening immune disorder

Newborn screening test can detect life-threatening immune disorder

 

Severe combined immunodeficiency (SCID) is a life-threatening genetic disorder of newborns that leaves the immune system unable to defend against infectious disease. It’s been estimated that this condition occurs in 1 in every 100,000 births. At present the treatment is a transplant of healthy cells from a donor, which is best done soon after diagnosis to improve chances that the child will not be devastated by infections. Recently, attention has been drawn to the importance of routinely screening newborns for SCID because the disease is not easily detected at birth. In February, 2009, Massachusetts began a pilot program offering newborn screening for SCID for all new births.

 

In an upcoming issue of the Journal of Allergy and Clinical Immunology, found online now at http://www.jacionline.org, Comeau and colleagues from the Massachusetts SCID Newborn Screening Working Group report the first case of SCID identified during this pilot program after screening 100,597 babies. The condition was detected before the infant experienced any symptoms. The child was kept at home in isolation to protect from infection prior to the infant’s recent transplant. The Massachusetts group points out that this screening assay meets testing requirement for SCID and supports screening newborns for SCID as an important step toward protecting children against this disease.

 

Jaime E. Hale, BS, Francisco A. Bonilla, MD, PhD, Sung-Yun Pai, MD, Jacalyn L. Gerstel-Thompson, MS, Luigi D. Notarangelo, MD, Roger B. Eaton, PhD, Anne Marie Comeau, PhD

 

 

The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

 

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Glaxo Turns its Eye to ‘Bubble Boy Disease’ in Rare Disease Push.

Glaxo Turns its Eye to ‘Bubble Boy Disease’ in Rare Disease Push.

By Jeanne Whalen
GlaxoSmithKline strengthened its focus on rare diseases today by targeting one of the rarest: ADA severe combined immune deficiency, one form of so-called “bubble boy disease.”

ADA-SCID, which affects only about 350 children worldwide, is caused by a genetic defect that leaves kids without a functioning immune system, making them extremely vulnerable to infection and early death.

The standard treatment today is a bone marrow transplant, which gives the patient new stem cells that, with luck, will start producing the blood cells needed to make the immune system function. But closely matched donors are hard to find, and the patient’s body often rejects the transplanted cells.

Glaxo has licensed an experimental gene therapy from two Italian institutions that aims to fix the stem cells in the patient’s own bone marrow. Stem cells are removed and a healthy gene is inserted before the cells are returned to the body. Glaxo and its partners believe that using the patient’s own cells will reduce the risk of rejection.

The therapy has demonstrated “potential” in phase 1 and 2 studies, Glaxo says. The drug giant and the two institutions — Fondazione Telethon and Fondazione San Raffaele — plan to see if the same technique might be used in treatments for a range of other rare diseases, from metachromatic leukodystropy to Wiskott-Aldrich Syndrome. (Trials for those two diseases are now recruiting patients.)

The partnership is part of Glaxo’s growing push into the rare disease market, Marc Dunoyer, global head of rare diseases, told journalists on a conference call today. About 70% of the 6,000-8,000 rare diseases that have been identified have genetic origins, and many have clear molecular targets. As Dow Jones Newswires reports, Dunoyer said his rare disease unit will focus on four areas: metabolism, immuno-inflammation, central nervous system and hematology. DJN notes that “he declined to say how much money the division would spend or whether acquisitions were part of its drug development strategy.”

linkback url: http://blogs.wsj.com/health/2010/10/18/glaxo-turns-its-eye-to-bubble-boy-disease-in-rare-disease-push/

Rare disorder demands quick intervention

Rare disorder demands quick intervention

Siblings’ disparate outcomes are emblematic of how important an early diagnosis can be

By KELLY BOTHUM • The News Journal • October 12, 2010

Both of Donna Sawyer’s children were born with the same life-threatening immune disorder that left their tiny bodies susceptible to infections from even minor viruses, bacteria and fungi.

Today, her 12-year-old son, Austin, is a Boy Scout, baseball player and straight-A student at Conrad School of the Sciences. Her daughter, Alex, who is 15, has cognitive deficits and is in special education classes at Christiana High School. She has gone through years of speech, physical and occupational therapies, yet still struggles with physical limitations on her left side caused by a stroke she suffered at 9 months old.

The difference between her children’s outcomes, Sawyer said, is early detection. Austin and Alex have severe combined immunodeficiency, or SCID, a rare condition in which patients are essentially born without a functioning immune system. As a result, they can’t fight off the germs the same way as someone with a functioning immune system. Without treatment, children born with SCID rarely live past their 2nd birthday.

Alex was 9 months old before she was diagnosed with SCID, believed to occur once in every 100,000 births. In that time, she battled repeated ear infections, diarrhea and vomiting, and never seemed to get better. After her diagnosis, she underwent a bone marrow transplant and slowly began to recover, but not before her body went into organ failure. She spent two months on life support and suffered a massive stroke that left her with permanent damage to her brain and the left side of her body.

Because of Alex’s diagnosis, Austin was screened at birth for the genetic disorder. Like his sister, he underwent a bone marrow transplant at Duke University, but suffered none of the complications she did.

“Today, his quality of life is much better than Alex,” said Sawyer, who lives in Newark. “Life is going to be a struggle for her.”

Sawyer hopes to save other children from what Alex experienced by getting SCID added to the panel of diseases newborns are screened for in Delaware.

Bubble boy disease

SCID was once known as “bubble boy disease.” Patient David Vetter gained worldwide attention in the 1980s after a movie was made about his experiences living more than a decade in a sterile bubble to reduce his vulnerability to infection. Vetter died in 1984 after an unsuccessful bone marrow transplant.

Dr. Stephen McGeady, interim chief of the division of allergy and immunology at Alfred I. duPont Hospital for Children, calls SCID a “pediatric emergency” because of the severity of illness in babies born with the rare group of inherited disorders.

In a normal developing immune system, specialized cells mount a response to what the body perceives as foreign invaders. Antibodies attack these invading viruses, bacteria and fungi, generating an immune response. But in patients with SCID, there are defects in these immune responses, so children can’t fight off even minor infections. Children with SCID are at a higher risk of chronic ear infections, thrush and other yeast infections, as well as bronchitis and pneumonia.

Because they lack natural immune defenses — imagine a fighter going into battle without protective armor — these kids seem to stay sick, as they are bombarded with viruses and bacteria that their bodies cannot defend against, said McGeady, who has seen just two cases of SCID in more than a decade at the hospital. In both cases, the patients eventually died.

SCID is one of about 150 kinds of primary immune disorders that are believed to affect 250,000 people in the United States, said Christine Belser, senior director of programs and education at the Immune Deficiency Foundation in Towson, Md.

“One of the biggest problems is that people get a very late diagnosis because only the symptoms are treated. The root cause is not,” Belser said. “You can’t take away the harm that has been done. The important thing is having this diagnosis as early as possible so the right kind of treatment is done.”
Marrow transplants

From the time Alex was about 2 months old, she was always sick. Initially, the first-time parents chalked up the problem to their daughter being in day care. They kept taking her to the pediatrician, but she never seemed to improve despite medications and antibiotics. By the time she was diagnosed at 9 months old, Alex was critically ill. She wound up at Duke University Medical Center, where she had a bone marrow transplant. Her mother was her donor.

“They told us she would not make it through the night. It was just gut-wrenching,” said Sawyer, who said the bill for Alex’s care was more than $1 million. “Little by little, she made it through and started to improve.”

Since their transplants, Alex and Austin, who also had a transplant with marrow donated by Sawyer, show no immunological problems associated with SCID. They return annually to Duke for immune studies.

Sawyer hopes to prevent other children from experiencing what Alex did. Adding SCID to the list of diseases newborns are screened for in Delaware would make that possible, she said, even if it means only one or two children would be diagnosed.

Nationwide, state newborn screening programs test about 4 million babies each year for genetic and metabolic disorders. These are conditions that wouldn’t otherwise be apparent in a newborn. About 12,000 babies are screened annually in Delaware.

In January, a federal advisory committee recommended the addition of SCID to the uniform newborn screening panel. Six months later, the American Academy of Pediatrics made a similar recommendation.

In order to add SCID to the newborn screening panel in Delaware, the state would have to pass legislation mandating the test, said Leah Jones, chief of the maternal and child health bureau with the Delaware Division of Public Health. Delaware currently tests for more than 30 disorders, using a sample of blood taken from a heel stick on the baby.

DPH supports adding SCID testing to the panel, and is investigating the cost of adding equipment and staffing for the additional laboratory testing, Jones said.

Sawyer knows the impact of early diagnosis, both in terms of intervention and medical cost. She hopes to convince state health officials as well.

“It’s something that makes such a difference,” Sawyer said. “I see my kids and I know that.”

linkback url; http://www.delawareonline.com/article/20101012/HEALTH/10120303/Rare-disorder-demands-quick-intervention

NIH funds Center of Excellence for Molecular Hematology at Cincinnati Children’s

NIH funds Center of Excellence for Molecular Hematology at Cincinnati Children’s

CINCINNATI – Cincinnati Children’s Hospital Medical Center has been named one of five national Centers of Excellence for Molecular Hematology to find new gene and cell therapies for inherited diseases affecting blood cells.

The National Institute of Diabetes, Digestive and Kidney Diseases, one of 19 National Institutes of Health, has approved a five-year, $3.4 million grant for Cincinnati Children’s to establish the multi-disciplinary center. The center blends Cincinnati Children’s extensive research and clinical expertise, including its close collaboration with research affiliate, the University of Cincinnati College of Medicine.

A key aim of the Cincinnati Center for Molecular Hematology is to accelerate the discovery of new therapeutic approaches for conditions like sickle cell anemia, thalessemia, leukemia, immunological disorders and other blood cell-based diseases, according to Yi Zheng, Ph.D., director of Experimental Hematology and Cancer Biology and director of the new center. The center will also help speed the transition of new therapies from the research laboratory to clinical trials.

“We have a strong basic research pipeline at Cincinnati Children’s and the ability to rapidly translate basic research into the clinic,” Dr. Zheng said. “The medical center is one of the few institutions in the country that can claim excellence in basic science, expertise in genetic manipulation under Good Manufacturing Practice conditions, and also provide outstanding cell and gene therapies and patient care at a single location.”

The challenge is to understand and correct diseases caused by interactions between mutated genes and environmental factors that adversely affect blood cells. Researchers believe that successfully applying molecular and cell therapeutics to blood cells that can be transplanted into patients will provide life-long cures for inherited diseases.

Cincinnati Children’s is already working on gene therapy trials for new treatments of sickle cell anemia, X-SCID (X-linked severe combined immunodeficiency), solid cancers such as rhabdomyosarcoma and Ewing’s sarcoma, and a number of other diseases.

The NIDDK grant helps fund four research cores that support the research activities of multiple investigators. The cores are vital to the rapid and efficient translation of original discoveries from the laboratory to the clinic, Dr. Zheng said

The research cores supported by the grant are:

* The Translational Core. The core includes 10,000-square-feet of tightly controlled “clean room” laboratory space. The facility can manipulate human cells outside of the body to create cell products for therapeutic use in specific diseases. It also produces viral vectors to allow the delivery of specific genetic information for treating disease
* The Genomics and Genetics Core. The core provides leading edge genomic analysis of blood cell diseases and determining the normal genetic traits of blood stem and progenitor (early stage) cells.
* The Mouse Xenotransplant/Transgenic Core. The core maintains specialized mouse strains and provides mouse transplant and transgenic services that allow scientists to study mouse models of human disease.
* The Flow Cytometry Core. This laboratory allows scientists to analyze and sort different types of blood cells.

The center designation comes after years of basic science discoveries in genetics and genomics have put researchers on the threshold of exciting new therapeutic approaches for blood cell disorders, according to Arnold Strauss, M.D., director of the Cincinnati Children’s Research Foundation, chief medical director of the medical center, and chair of pediatrics at the UC College of Medicine.

“We are on the verge of being able to use novel interventions to treat and really cure disorders, such as sickle cell anemia, that severely impair normal lives for children and adolescents and cause premature death in young adults,” Dr. Strauss said. “After 40 years of watching afflicted children suffer and die, I am incredibly excited that the time is arriving for their cure.”

Helping secure the center of excellence designation is a decade of rapid growth in Cincinnati Children’s research activities and in its reputation. The medical center is the nation’s second largest pediatric research organization as measured by NIH funding, which totaled over $115 million in fiscal 2009 – an increase from $12.3 million just a decade ago. The medical center currently has 950,000 square feet of research laboratory space, with plans underway for an additional 300,000 square feet.

The expansion has included establishment of nearly two dozen research cores, with capabilities ranging from creating and maintaining stem cell lines to one of the largest academic bioinformatics and computing centers in the nation.

linkback url http://www.eurekalert.org/pub_releases/2010-10/cchm-nfc100710.php