Navigation Links
Gene therapy achieves early success against hereditary bleeding disorder
Date:12/10/2011

(MEMPHIS, Tenn. December 10, 2011) Symptoms improved significantly in adults with the bleeding disorder hemophilia B following a single treatment with gene therapy developed by researchers at St. Jude Children's Research Hospital in Memphis and demonstrated to be safe in a clinical trial conducted at the University College London (UCL) in the U.K.

The findings of the six-person study mark the first proof that gene therapy can reduce disabling, painful bleeding episodes in patients with the inherited blood disorder. Results of the Phase I study appear in today's online edition of the New England Journal of Medicine. The research is also scheduled to be presented December 11 at the 53rd annual meeting of the American Society of Hematology in San Diego.

Four study participants stopped receiving protein injections to prevent bleeding episodes after undergoing the therapy and have not suffered spontaneous bleeding. Several have also participated in marathons and other activities that would have been difficult prior to gene therapy. The study volunteers were all treated at the Royal Free Hospital in London under the care of Edward G.D. Tuddenham, M.D., Ph.D., a pioneer in the field of blood coagulation and a study co-author.

"This is a potentially life-changing treatment for patients with this disease and an important milestone for the field of gene therapy. It could have ramifications for the treatment of hemophilia A, other protein and liver disorders and chronic diseases such as cystic fibrosis," said first author Amit Nathwani, M.D., Ph.D., a faculty member at the UCL Cancer Institute, Royal Free Hospital and NHS Blood and Transplant (NHSBT).

Hemophilia B is caused by an inherited mistake in the gene for making a protein called Factor IX, which is essential for normal blood clotting. The gene is carried on the X chromosome. As a result, hemophilia B is almost exclusively a disease of men. About 1 in 30,000 individuals inherit the mutation.

Previous efforts to ease hemophilia B symptoms by introducing a correct copy of the gene have been unsuccessful.

The current study used adeno-associated virus (AAV) 8 as the vector to deliver the Factor IX gene along with additional genetic material into the patient's liver. AAV8 was picked because the incidence of natural infection with AAV8 is low. It belongs to a family of viruses that target liver cells but do not cause disease in humans or integrate into human DNA. Participants in the study received no immune suppressing drugs prior to gene therapy.

This approach was jointly pioneered by St. Jude and UCL, initially in the laboratory of study co-author Arthur Nienhuis, M.D, a member of the St. Jude Department of Hematology.

For this study, each patient received a one-time infusion of the vector into a vein in the arm. Two patients each were treated with escalating doses of the vector. Following treatment, Factor IX levels rose in all six patients from less than 1 percent of normal levels prior to the gene therapy to between 2 and 12 percent.

Factor IX levels increased the most in the two study volunteers who received the highest dose of the experimental vector, researchers said. After treatment, levels of the protein ranged from 3 to 12 percent in those men. Even modest increases that raise Factor IX production to more than 1 percent of normal levels have the potential to dramatically affect a patient's quality of life and reduce bleeding episodes, said the study's senior author Andrew Davidoff, M.D., chair of the St. Jude Department of Surgery.

"The first patient has been followed for the longest time, and his levels have remained at 2 percent for more than 18 months. These results are highly encouraging and support continued research. More patients are scheduled to be enrolled in future trials scheduled to begin later this year," Davidoff said.

One of the participants who received the highest dose of the vector underwent successful, short-term steroid treatment after his liver enzymes rose slightly after the vector infusion. The rise signalled mild liver damage. The volunteer remained otherwise healthy, his Factor IX levels remain above pre-infusion levels and his liver enzymes have returned to normal. Liver enzymes also rose slightly, but remained in the normal range, for the other participant who received the highest dose of the vector. That participant also received a short course of steroids.

Researchers believe an immune response targeting the vector triggered the elevated enzyme levels. A similar response was reported in earlier gene therapy trials conducted by other investigators using a different vector.

The vector used in this study was produced at the Good Manufacturing Practices (GMP) facility on the St. Jude campus. The GMP operates under U.S. government-approved manufacturing guidelines and produces highly specialized medicines, vaccines and other products that pharmaceutical companies are reluctant to pursue. The vector can also now be produced in a similar facility at UCL.


'/>"/>

Contact: Carrie Strehlau
media@stjude.org
901-595-2295
St. Jude Children's Research Hospital
Source:Eurekalert

Related medicine news :

1. Nicotine replacement therapy is over-promoted since most ex-smokers quit unassisted
2. Social Anxiety and Panic - Alternative Treatment to Drugs and Therapy
3. Longview Therapy Center, PLLC, Unveils Its Definition Of Hope
4. Short-term radiation therapy successful on breast cancer
5. ASCROs Response to NY Times Articles on Radiation Therapy Incidents
6. Children With Cerebral Palsy Benefitting From New Physical Therapy Regimen
7. DavisPTnetwork Partners with the New York Physical Therapy Association to Provide Online Continuing Education
8. Behavioral therapy improves sleep and lives of patients with pain
9. WHI data confirm short-term heart disease risks of combination menopausal hormone therapy
10. Promising therapy for relapsing multibple sclerosis
11. Split-course palliative radiotherapy confirmed as effective treatment for advanced NSCLC
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/17/2017)... ... 2017 , ... Anesthesia Progress – Everyone wants less pain during ... option for each patient. Dentists have several general anesthesia alternatives and finding the right ... the Tokyo Dental College in Tokyo, Japan wanted to find out which anesthetic was ...
(Date:1/17/2017)... ... , ... For breast cancer clinicians and researchers who were unable to attend ... intimate review and analysis of its highlights, a novel half-day, complimentary meeting—the 14th Annual ... on February 4, 2017 in Chicago. Chaired by Kathy S. Albain, MD, FACP, FASCO ...
(Date:1/17/2017)... (PRWEB) , ... January 17, 2017 , ... SunView Software’s ... Award for Innovation of the Year. , Each year, Pink Elephant recognizes ... an innovative approach to address a specific business problem or opportunity. The award highlights ...
(Date:1/17/2017)... Chapel, Florida (PRWEB) , ... January 17, 2017 ... ... Connected City, a new 21st century approach to infusing high speed technology into ... an area exclusively dedicated to the advancement of healthcare and wellness in a ...
(Date:1/17/2017)... ... January 17, 2017 , ... Medic-CE ... EMS and firefighting professionals, has released four new continuing education courses as part ... taught live in an online classroom and meet the requirements of the National ...
Breaking Medicine News(10 mins):
(Date:1/18/2017)... 18, 2017  Tarix Orphan LLC today announced that ... Rare Pediatric Disease (RPD) designation for the company,s drug ... Bullosa (RDEB), a rare genetic skin disorder. There are ... limited to supportive care. "The RPD designation ... previously granted by the FDA in this indication," said ...
(Date:1/18/2017)... January 18, 2017 ML ... plans to publish an online presentation tomorrow, January ... sales forecast for 2017. Management reports that the ... record sales performance from its existing operations, and ... entry into the Cannabis sector through a ...
(Date:1/18/2017)...  Robust competition in the private marketplace is ... prices, according to a new study by ... the first to examine the share of prescription medicine ... managers (PBMs), health plans and other stakeholders in the ... first to show what happens when the list price ...
Breaking Medicine Technology: