Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Effective Gene Therapy for Children with Wiskott-Aldrich-Syndrome

11.11.2010
A Severe Inborn Immunodeficiency Disease: In a first application of gene therapy for the treatment of Wiskott-Aldrich Syndrome, blood forming bone marrow cells have been corrected by gene transfer in Hannover, Germany.

In a first application of gene therapy for the treatment of Wiskott-Aldrich Syndrome, blood forming bone marrow cells have been corrected by gene transfer in Hannover, Germany.

A team led by Professor Christoph Klein has succeeded in correcting symptoms of this rare, inherited immunodeficiency in 9 out of 10 children in a clinical trial. One patient did not receive a sufficient number of cells, and one patient unfortunately developed an acute T cell leukemia related to the treatment. In an article published in the New England Journal of Medicine this week, Klein and colleagues report on details of their trial’s two first patients with four years of follow-up. “We are delighted about the possibility to offer a new form of therapy to this group of patients” says Klein. “However, we have to proceed very carefully, because the inherent risks of the retrovirus vector technology can produce serious side effects, as occurred in one of our patients.” Earlier this year, Professor Klein received the renowned Leibniz Award of the German Research Foundation (DFG) for his work in pediatric immunology.

The Wiskott-Aldrich Syndrome
The first symptoms of Wiskott-Aldrich syndrome (WAS) occur in early childhood and include repeated serious infections, pneumonia, bleeding and rashes. WAS patients frequently develop autoimmune diseases, leukemia or lymphoma, and die of infectious complications when left untreated. Allogeneic blood stem cell (bone marrow) transplantation has been the only therapeutic option thus far. However, this approach requires a genetically matched donor and therefore, has not been available for all patients, and can produce serious side immunological side effects. “Immune complications of allogeneic stem cell transplantation can be quite severe in WAS patients” notes Dr. Kaan Boztug, a researcher in Christoph Klein’s team and first author of the New England Journal of Medicine article. The disease is caused by a genetic mutation disturbing the formation of the Wiskott-Aldrich Syndrome protein (WASP). The protein is important for a functional cytoskeleton, which is required for maturation and activation of white blood cells forming the immune system and platelets required for blood clotting. The researchers could demonstrate by several tests that gene transfer can restore cytoskeletal function.
Treatment by transfer of a normal gene
The Wiskott-Aldrich Syndrome (WAS) gene is located on the X chromosome, and therefore the disease is exclusively found in boys, such as the five-year old Felix Ott. Shortly after being born in 2005, he had to be admitted to the intensive care unit because of severe bleeding. The diagnosis Wiskott-Aldrich Syndrome was made later, at age three. At this point, Felix’s pediatrician anticipated a bad prognosis. In 2009, Felix received stem cell gene therapy. The researchers purified hematopoietic stem cells and corrected the genetic defect by introducing a healthy copy of the WAS gene using a retroviral vector. The genetically modified cells were reinfused and started to produce normal blood cells. Within a year after gene therapy, Felix´s corrected bone marrow generated functional platelets and white blood cells. The symptoms caused by dysfunctional blood cells completely resolved. He now enjoys a normal life and his father Oliver is quite joyful: “Today, Felix can play with other children and we don’t have to handle him with kid gloves any more”.
Possibilities and risks of gene therapy
For gene therapy, missing genetic information is transferred into body cells to reconstitute the diseased cells’ ability to produce a vital protein from the transferred code. Nature itself provides very efficient gene ferries in the form of viruses. For gene therapy, the genetic information for making viral proteins is removed, and replaced by the healthy WAS gene. Ideally, a single application is sufficient for replacing gene function, and might avoid the necessity for lifelong medication.
Even though gene therapy is a simple concept, in clinical reality it requires a complex medical treatment and is associated not only with great potential but also with significant risks. Patient safety is a top priority in the pursuit of possibilities to cure rare diseases. Unwanted side effects of gene vector integration into the genome of cells include the activation of cellular genes involved in initiating cancer. Tight monitoring of bone marrow function for side effects is of great importance for the successful conduct of gene therapy trials. Prof. Christof von Kalle at the National Center for Tumor Diseases (NCT) in Heidelberg, Germany is an internationally renowned expert in gene therapy vector monitoring. His team regularly studies the treated WAS patients’ cells for activation of cancer associated genes. “While we did not discover very large imbalances of cell growth in the first patients, this does not yet exclude more serious side effects developing later.” First studies in cells from the leukemic patient seem to indicate that the therapeutic vectors have caused the initial stages of this severe side effect, which also occurred in previous gene therapy trials in Paris and London.
“New gene vectors can potentially prevent such side effects, but have not been available in a clinically usable format,” says Klein. “We do hope that this technology will be available one year from now for the next generation of this trial.”

Prior to clinical application of this gene therapy Klein’s interdisciplinary team has closely worked with philosophers and bioethicists. “For our WAS children without suitable transplant donors, gene therapy offers a chance to return to a normal life, as Felix’s example shows,” explains Klein.

Care for Rare Foundation
Professor Christoph Klein and colleagues have established the Care-for-Rare-Foundation aiming to help children with rare diseases by promoting translational scientific studies and by enabling rapid access to state-of-the-art genetic diagnosis and innovative therapies. The Care-for-Rare Foundation collaborates with an international network of physicians and scientists and has a current focus on rare diseases of the immune system (www.care-for-rare.org).

Further information: Professor Christoph Klein, klein.christoph@mh-hannover.de, phone +49 511 532-6711

Stefan Zorn | idw
Further information:
http://www.care-for-rare.org
http://www.mh-hannover.de/

More articles from Health and Medicine:

nachricht Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Party discipline for jumping genes

22.09.2017 | Life Sciences

The pyrenoid is a carbon-fixing liquid droplet

22.09.2017 | Life Sciences

Comet or asteroid? Hubble discovers that a unique object is a binary

21.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>