Gene Therapy/Stem Cell Treatment Cures Boys of Severe Genetic Disease

British doctors have successfully cured youngsters suffering from a deadly inherited genetic disorder using ground-breaking stem cell-based treatments. This is the harbinger of a new era of medicine and genetic therapies.

The young patients who participated in this trial suffer from the most severe form of a rare blood condition call “Wiskott-Aldrich Syndrome.” The trial participants have now been free of the disease for four years.

Patients with Wiskott-Aldrich syndrome are usually male, and they have a deficient immune system that fails to fight off common infections that usually do not affect most people and a reduced ability to form blood clots. The numbers, and size of platelets in the blood, which are the cells responsible for initiating blood clots, are abnormal in individuals with Wiskott-Aldrich syndrome; they have very small platelets and few of them. This condition is called microthrombocytopenia. This platelet abnormality leads to easy bruising or episodes of prolonged bleeding following minor traumas. Additionally, many types of white blood cells are abnormal or nonfunctional, and this increases the risk of several immune and inflammatory disorders. Often patients with Wiskott-Aldrich syndrome develop eczema, which is an inflammatory skin disorder characterized by abnormal patches of red, irritated skin. Affected individuals also have an increased susceptibility to infection, and developing autoimmune disorders. They also have an increased chance of developing some types of cancer, such as cancer of the immune system cells (lymphoma).

Wiskott-Aldrich syndrome is inherited from the X chromosome, and therefore, the condition is much more common in males than in females. Having said that, Wiskott-Aldrich syndrome is still a rather rare condition, with an estimated incidence of 1 – 10 cases per million males worldwide.

Mutations in the WAS gene cause Wiskott-Aldrich syndrome. The WAS gene encodes the WASP protein, which is found in all blood cells, and relays signals from the surface of blood cells to the actin cytoskeleton inside the cell. The actin cytoskeleton is a network of fibrous proteins that compose the cell’s interior structural framework. WASP signaling triggers cell movement and attachment to other cells and tissues. In white blood cells, WASP signaling induces the actin cytoskeleton to establish the interactions between cells and the foreign invaders targeted by them. Mutations in the WAS gene cause a lack of any functional WASP protein, and loss of WASP signaling. Thus white blood cells are less able to respond to foreign invaders, which cause many of the immune problems related to Wiskott-Aldrich syndrome. Similarly, decreased WASP function impairs platelet development, leading to reduced size and early cell death.

In the Britain, Wiskott-Aldrich syndrome affects fewer than one hundred children in Britain, but Daniel Wheeler, 15, of Bristol is one of them. Wheeler was among seven children who participated in the new gene therapy trial at centers in London and Paris.

Daniel was diagnosed with Wiskott-Aldrich syndrome when he was two years old and needed frequent medical care to manage his symptoms which included severe eczema, asthma and inability to fight infections. David’s older brother died from complications associated with the disease. However, since undergoing gene therapy in 2011 Daniel has shown no symptoms and doctors believe he is effectively cured.

Daniel’s mother Sarah, 50, who works in real estate in Bristol said: “Since being around two, Daniel has been in an out of hospital, but now his skin has cleared up and so has his asthma. It means he can get on with his life now.”

Adrian Thrasher, Professor in Pediatric Immunology, at Great Ormond Street Hospital in London, where David’s treatment was carried out, said that it offered new hope for people suffering from incurable disease. “We are entering a new era where genetic treatments are entering mainstream medicine and offering hope to patients for whom conventional treatments don’t work well or are simply unavailable,” he said.

“The work shows that this method is successful in patients who, in the past would have very little chance of survival without a well match bone marrow donor.

“It also excitingly demonstrates the potential for treatment of a large number of other diseases for which existing therapies are either unsatisfactory or unavailable.”

In this trial, David’s bone marrow stem cells were isolated and subjected to gene therapy in the laboratory. The faulty WAS gene was replaced with a healthy copy of the gene. These genetically repaired stem cells were replaced in David’s bone marrow where they began producing healthy blood cells that were free from the disease. Because the healthy blood cells were more durable and lived longer than the diseases ones, they eventually overtook the diseased ones.

Seven children between the ages of eight months and 15 years were selected for the trial because a bone marrow match could not be found. Without bone marrow transplantation, patients usually do not survive their teenage years. All the children had eczema and associated recurrent infections and most experienced severe bleeding and autoimmune disease that, in one case, confined the child to a wheelchair.

The children went from spending an average of 25 days in the hospital to no days in the hospital in the two years after the treatment. Furthermore the child using the wheelchair was able to walk again.

Fulvio Mavilio, Chief Scientific Officer at Genethon, the biotech company which developed the treatment said: “It is the first time that a gene therapy based on genetically modified stem cells is tested in an international clinical trial that shows a reproducible and robust therapeutic effect in different centers and different countries.”


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Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).