PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Gene therapy provides safe, long-term relief for patients with severe hemophilia B

Gene therapy pioneered by St. Jude Children's Research Hospital, University College London and the Royal Free Hospital provides men with hemophilia B reliable relief from the bleeding disorder

2014-11-20
(Press-News.org) (MEMPHIS, Tenn. - November 19, 2014) Gene therapy developed at St. Jude Children's Research Hospital, University College London (UCL) and the Royal Free Hospital has transformed life for men with a severe form of hemophilia B by providing a safe, reliable source of the blood clotting protein Factor IX that has allowed some to adopt a more active lifestyle, researchers reported. The results appear in the November 20 edition of The New England Journal of Medicine.

In this study, participants received one of three doses of gene therapy that used a modified adeno-associated virus (AAV) 8 as the vector to deliver the genetic material for making Factor IX. The vector was administered as a single infusion into a peripheral vein in the arm of each participant.

Factor IX levels rose in all 10 men with severe hemophilia B following gene therapy and have remained stable for more than four years. Overall, episodes of spontaneous bleeding declined 90 percent. Use of Factor IX replacement therapy dropped about 92 percent in the first 12 months after the treatment with the investigational therapy.

In the six participants who received the highest gene therapy dose, levels of the blood-clotting protein increased from less than 1 percent of normal levels to 5 percent or more. The increase transformed their disease from severe to mild and enabled participation in sports such as soccer without the need for Factor IX replacement therapy or an increase in the risk of bleeding. Episodes of spontaneous bleeding and use of Factor IX replacement therapy declined for these patients more than 94 percent in the next 12 months.

Liver enzymes rose in four of the six patients who received the highest dose, possibly due to an immune response against the vector. The men had no symptoms and remained otherwise healthy. Their liver enzymes returned to the normal range following brief treatment with steroids.

Hemophilia B is caused by a mutation in the Factor IX gene that can result in dangerously low levels of the essential clotting protein. The disorder affects about 1 in 30,000 individuals, mostly men. For those with severe disease marked by Factor IX levels less than 1 percent of normal, scrapes and bumps are medical emergencies. Painful episodes of spontaneous bleeding can result in crippling joint damage early in life and an increased risk of potentially fatal bleeding within the brain.

"This study provides the first clear demonstration of the long-term safety and efficacy of gene therapy," said senior author Andrew Davidoff, M.D., chair of the St. Jude Department of Surgery. "The results so far have made a profound difference in the lives of study participants by dramatically reducing their risk of bleeding."

The paper's first and corresponding author, Amit Nathwani, M.D., Ph.D., added: "The data we are reporting mark a paradigm shift in treatment of hemophilia B and lay the groundwork for curing this major bleeding disorder." Nathwani is a faculty member at the UCL Cancer Institute, Royal Free Hospital and NHS Blood and Transplant. "The results also provide a solid platform for developing this gene transfer approach for treatment of other disorders ranging from other congenital clotting deficiencies like hemophilia A to inborn errors of metabolism such as phenylketonuria."

Prior to receiving gene therapy, seven of the 10 men received Factor IX replacement therapy at least once a week in order to prevent bleeding episodes. Others used replacement therapy as needed to halt bleeding or prior to surgeries.

Since joining the trial, four of the seven men ended the routine Factor IX injections. None have suffered spontaneous bleeding despite increased physical activity. "Some patients have not required clotting factor injections for more four years, which has been life changing," Nathwani said. Researchers estimated that overall spending on Factor IX replacement therapy for study participants is down more than $2.5 million.

Factor IX is normally produced by liver cells. AAV8 was selected for the vector because the virus infects liver cells but does not cause disease in humans or integrate into human DNA. This study was restricted to patients not previously infected with AAV8 to eliminate the need for immune-suppressing drugs to protect the vector from possible immune system attack.

The vector was developed by the St. Jude-UCL collaboration and produced at the Children's Good Manufacturing Practices (GMP), LLC, on the St. Jude campus. The Children's GMP operates under U.S. government-approved manufacturing guidelines and is also complaint with European Union manufacturing requirements. It produces highly specialized medicines, vaccines and other products that are in the early stages of development.

Twelve men have now joined the on-going Phase I/II safety and efficacy trial. Half were treated at UCL and half at St. Jude. Discussions are underway about expanding the trial to include younger patients with hemophilia B. Meanwhile work continues to improve and expand use of the vector for treatment of hemophilia A, another more common bleeding disorder.

INFORMATION:

Other authors are Ulrike Reiss, Catherine Y.C. Ng, Junfang Zhou, Maria Cancio, Christopher Morton, Deokumar Srivastava and Arthur Nienhuis, all of St. Jude; John Gray and James Allay, both formerly of St. Jude; Edward G.D. Tuddenham, Pratima Chowdary, Jenny McIntosh, Anne Riddell and Jun Pie, all of Royal Free NHS Trust; Cecilia Rosales, Marco Della Peruta, Elsa Lheriteau, Nishal Patel and Deepak Raj, all of UCL Cancer Institute; Savita Rangarajan and David Bevan, both of St. Thomas Hospital, London; Michael Recht, Oregon Health & Science University, Portland, Ore.; Yu-Min Shen, University of Texas Southwestern Medical Center, Dallas; Kathleen Halka, Temple Clinic, Temple, Texas; Etiena Basner-Tschakarjan, Federico Mingozzi and Katherine High, all of Children's Hospital of Philadelphia; and Mark Kay, Stanford University, Palo Alto, Calif.

In the U.S., the research was funded by a grant (HL094396) from the National Heart, Lung, and Blood Institute at the National Institutes of Health; the Assisi Foundation of Memphis; Howard Hughes Medical Institute and ALSAC. In the U.K., the research was founded in part by the Medical Research Council, The Katharine Dormandy Trust; NHS Blood and Transplant; UCLH/UCL NIHR Biomedical Research Centre; The Royal Free Hospital Charity and a NIHR Programme Grant.

St. Jude Media Relations Contacts Carrie Strehlau
desk (901) 595-2295
cell (901) 297-9875
carrie.strehlau@stjude.org

Summer Freeman
desk (901) 595-3061
cell (901) 297-9861
summer.freeman@stjude.org

St. Jude Children's Research Hospital St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20 percent to 80 percent since the hospital opened more than 50 years ago. St. Jude is working to increase the overall survival rate for childhood cancer to 90 percent in the next decade. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. Families never receive a bill from St. Jude for treatment, travel, housing and food--because all a family should worry about is helping their child live. To learn more, visit stjude.org or follow St. Jude at @stjuderesearch.

UCL Media Relations Contacts
Harry Dayantis
+44(0)20 3108 3844
h.dayantis@ucl.ac.uk

About UCL (University College London) Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. We are among the world's top universities, as reflected by performance in a range of international rankings and tables. UCL currently has almost 29,000 students from 150 countries and in the region of 10,000 employees. Our annual income is more than £900 million. http://www.ucl.ac.uk About the Royal Free London NHS Foundation Trust The Royal Free began as a pioneering organization and continues to play a leading role in the care of patients. Our mission is to provide world class expertise and local care. In the 21st century, the Royal Free London continues to lead improvements in healthcare. The Royal Free London attracts patients from across the country and beyond to its specialist services in liver, kidney and bone marrow transplantation, hemophilia, renal, HIV, infectious diseases, plastic surgery, immunology, vascular surgery, cardiology, amyloidosis and scleroderma and we are a member of the academic health science partnership UCL Partners. In July 2014 Barnet Hospital and Chase Farm Hospital became part of the Royal Free London. For further information, visit http://www.royalfree.nhs.uk.



ELSE PRESS RELEASES FROM THIS DATE:

NTU Singapore develops novel 2-in-1 biomarker and drug delivery system

NTU Singapore develops novel 2-in-1 biomarker and drug delivery system
2014-11-20
Nanyang Technological University in Singapore (NTU Singapore) has invented a unique biomarker with two exceptional functions. First, it lights up when it detects tumour cells to allow scientists to take a better look. And it can also release anti-cancer drugs at the same time to the specific cells. This new biomarker, which has immense potential for drug development, is made from a nanophosphor particle, ten thousand times smaller than a grain of sand. NTU Singapore associate professors Zhang Qichun and Joachim Loo have found a way to make the nanoparticle light up ...

A path to brighter images and more efficient LCD displays

A path to brighter images and more efficient LCD displays
2014-11-20
SALT LAKE CITY, Nov. 20, 2014 - University of Utah engineers have developed a polarizing filter that allows in more light, leading the way for mobile device displays that last much longer on a single battery charge and cameras that can shoot in dim light. Polarizers are indispensable in digital photography and LCD displays, but they block enormous amounts of light, wasting energy and making it more difficult to photograph in low light. The Utah electrical and computer engineering researchers created the filter by etching a silicon wafer with nanoscale pillars and holes ...

How fallopian tubes carry eggs unidirectionally

How fallopian tubes carry eggs unidirectionally
2014-11-20
Researchers in Japan have revealed the mechanism that determines the direction of the transportation of eggs in the fallopian tube. Fallopian tubes, or oviducts, connect the ovaries and uterus. They are also the place where the egg and sperm meet and fertilization occurs, in addition the tubes have the ability to carry the eggs/embryos to the uterus. Because of these important roles they are an absolutely essential part of the reproductive system. The luminal cells of the fallopian tubes have cilia (hair-like structures) on their surfaces, and by the ciliary movement ...

Oat oil preparation makes you feel fuller

Oat oil preparation makes you feel fuller
2014-11-20
Oats contain more fat than other cereals, and oat oil has a unique composition. A new study from Lund University, Härröd Research and Swedish Oat Fiber AB, shows a special oat oil preparation can produce greater satiety. The study followed 34 healthy individuals who were given different quantities of the oat oil preparation as part of a normal breakfast. The researchers found that levels of satiety hormones in the intestines rose more with the oat oil preparation than with the placebo 3-7 hours after the meal (by anything from a tenth to half, depending on the ...

In full view

In full view
2014-11-20
If you planned to sabotage a factory, a recon trip through the premises would probably be much more useful than just peeping in at the windows. Scientists looking to understand - and potentially thwart - the influenza virus have now gone from a similar window-based view to the full factory tour, thanks to the first complete structure of one of the flu virus' key machines. The structure, obtained by scientists at the European Molecular Biology Laboratory (EMBL) in Grenoble, France, allows researchers to finally understand how the machine works as a whole. Published today ...

Versatile bonding for lightweight components

Versatile bonding for lightweight components
2014-11-20
Shedding pounds is all the rage these days and the global trend toward weight reduction has even spread to the automobile industry. Cars are to get even lighter - using new materials such as ultra-high-strength steels or carbon, and carbon-fiber-reinforced plastics (CFRP). But no matter which diet regime and which lightweight components manufacturers choose, they all want the same thing: the best and longest-lasting joining method for vehicle components. Since Duroplast, which often serves as the matrix component for CFRPs, can't be welded, another joining technique is ...

Climate change will slow China's progress in reducing infectioius diseases

2014-11-20
China has made significant progress increasing access to tap water and sanitation services, and has sharply reduced the burden of waterborne and water-related infectious diseases over the past two decades. However, in a study published in the latest edition of Nature Climate Change, researchers from Emory University found that climate change will blunt China's efforts at further reducing these diseases in the decades to come. The study found that by 2030, changes to the global climate could delay China's progress reducing diarrheal and vector-borne diseases by up to seven ...

Professional majors strengthen the mission of liberal arts colleges

2014-11-20
Faced with declining enrollment and rising costs, some small liberal arts colleges have added professional and vocational majors, a decision University of Iowa researchers say has strengthened rather than undermined the mission of the schools. In fact, students at liberal arts colleges realized virtually the same educational gains, no matter their major, according to the UI report released earlier this month. The only differences were liberal arts major expressed a greater interest in literacy while professional majors scored higher in leadership skills. "Essentially, ...

MSK team makes key discovery in understanding immunotherapy's successes -- and its failures

2014-11-20
A collaborative team of leaders in the field of cancer immunology from Memorial Sloan Kettering Cancer Center has made a key discovery that advances the understanding of why some patients respond to ipilimumab, an immunotherapy drug, while others do not. MSK was at the forefront of the clinical research that brought this CTLA-4 blocking antibody to melanoma patients. A report published online first today in the New England Journal of Medicine shows that in patients who respond to ipilimumab, their cancer cells carry a high number of gene mutations--some of which make ...

Three drugs may be better than one for certain patients with advanced colorectal cancer

2014-11-20
Barcelona, Spain: Patients with a form of advanced colorectal cancer that is driven by a mutated version of the BRAF gene have limited treatment options available. However, results from a multi-centre clinical trial suggest that the cancer may respond to a combination of three targeted drugs. Professor Josep Tabernero, head of the medical oncology department at Vall d'Hebron University Hospital and director of the Vall d'Hebron Institute of Oncology, Barcelona, Spain, will tell the 26th EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics in Barcelona ...

LAST 30 PRESS RELEASES:

Call for papers: 14th Asia-Pacific Conference on Transportation and the Environment (APTE 2025)

A novel disturbance rejection optimal guidance method for enhancing precision landing performance of reusable rockets

New scan method unveils lung function secrets

Searching for hidden medieval stories from the island of the Sagas

Breakthrough study reveals bumetanide treatment restores early social communication in fragile X syndrome mouse model

Neuroscience leader reveals oxytocin's crucial role beyond the 'love hormone' label

Twelve questions to ask your doctor for better brain health in the new year

Microelectronics Science Research Centers to lead charge on next-generation designs and prototypes

Study identifies genetic cause for yellow nail syndrome

New drug to prevent migraine may start working right away

Good news for people with MS: COVID-19 infection not tied to worsening symptoms

Department of Energy announces $179 million for Microelectronics Science Research Centers

Human-related activities continue to threaten global climate and productivity

Public shows greater acceptance of RSV vaccine as vaccine hesitancy appears to have plateaued

Unraveling the power and influence of language

Gene editing tool reduces Alzheimer’s plaque precursor in mice

TNF inhibitors prevent complications in kids with Crohn's disease, recommended as first-line therapies

Twisted Edison: Bright, elliptically polarized incandescent light

Structural cell protein also directly regulates gene transcription

Breaking boundaries: Researchers isolate quantum coherence in classical light systems

Brain map clarifies neuronal connectivity behind motor function

Researchers find compromised indoor air in homes following Marshall Fire

Months after Colorado's Marshall Fire, residents of surviving homes reported health symptoms, poor air quality

Identification of chemical constituents and blood-absorbed components of Shenqi Fuzheng extract based on UPLC-triple-TOF/MS technology

'Glass fences' hinder Japanese female faculty in international research, study finds

Vector winds forecast by numerical weather prediction models still in need of optimization

New research identifies key cellular mechanism driving Alzheimer’s disease

Trends in buprenorphine dispensing among adolescents and young adults in the US

Emergency department physicians vary widely in their likelihood of hospitalizing a patient, even within the same facility

Firearm and motor vehicle pediatric deaths— intersections of age, sex, race, and ethnicity

[Press-News.org] Gene therapy provides safe, long-term relief for patients with severe hemophilia B
Gene therapy pioneered by St. Jude Children's Research Hospital, University College London and the Royal Free Hospital provides men with hemophilia B reliable relief from the bleeding disorder