Using antibody in treatment of 'bubble boy disease' shows early promise

March 1, 2018 by Christopher Vaughan, Stanford University Medical Center

Researchers at the School of Medicine said they are encouraged by early results from a clinical trial in which participants are being given an antibody-based treatment rather than chemotherapy or radiation to prepare them for a blood stem cell transplant.

The trial is the first time that the approach has been tested in humans. The researchers noted that these are preliminary results from the first two participants in the trial. Judith Shizuru, MD, Ph.D., professor of medicine, discussed the trial Feb. 27 at the annual meeting of Stanford's Center for Definitive and Curative Medicine.

The phase-1 trial involves participants who have a condition known as severe combined immunodeficiency. SCID, also known as "bubble boy disease," is a genetic disorder that disturbs the normal development of immune cells, leaving people with the condition vulnerable to infections that most people ward off easily.

SCID patients can be given infusions of stem and progenitor blood-forming cells to boost their immune response, but that effect can wear off over time if significant numbers of the healthy can't replace the diseased stem cells. The only cure for SCID involves a blood , in which the patient's defective stem cells are wiped out with chemotherapy or radiation so that large numbers of normal from a donor can take their place.

The problem with chemotherapy or radiation is that they can be very damaging. "Physicians often choose not to give chemotherapy or radiation to young children with SCID because there are lifelong effects: neurological impairment, growth delays, infertility, risk of cancer, etc.," Shizuru said.

Administering an antibody

The current trial is testing a different method of removing the defective stem cells. Shizuru and her colleagues—including Rajni Agarwal, MD, associate professor of pediatrics; and Maria Grazia Roncarolo, MD, Ph.D., professor of medicine and of pediatrics and co-director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine—are giving the participants an antibody to CD117, a cell surface marker found on blood and immune stem cells.

The potential therapy is based on work originating in the laboratory of Irving Weissman, MD, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine. Assistant professor of pediatrics Agnieska Czechowicz, MD, Ph.D., while still a graduate student in Weissman's lab, showed that an antibody could be used to block, in mice, a critical stem cell factor from binding to the receptor CD117. This binding had been previously shown in the Weissman lab to be required to keep blood stem cells alive. The use of the antibody could thereby eliminate most blood stem cells, clearing the way for donor stem cells to take up residence in the bone marrow.

Early data from the clinical trial show that the antibody's activity in humans is similar to what was observed in mouse studies. Specifically, the antibody appears to be effective in the depletion of genetically defective stem cells.

Nine and six months after the treatment, respectively, the two participants have shown evidence that the donor stem cells have taken root and are producing , Shizuru said.

Given these results, the researchers plan to continue their clinical trial and include infants with the disease, since infancy is a time when the negative effects of chemotherapy or radiation can be particularly acute.

The first cases also suggest that the antibody-based conditioning may be useful in combating other diseases, including cancer, Shizuru said. Autoimmune diseases like Type 1 diabetes, multiple sclerosis and lupus may be curable through stem cell transplantation, but are not currently treated this way because the dangers of chemotherapy or radiation usually outweigh the benefits.

Explore further: Less toxic bone marrow transplants on horizon

Related Stories

Less toxic bone marrow transplants on horizon

August 10, 2016
Bone marrow transplants that do not require dangerous and often toxic chemotherapy could soon be possible, US researchers said Wednesday after seeing initial success with experiments on mice.

Study suggests hope for a longer life for patients with rare autoimmune disorder

January 17, 2018
An unusual autoimmune disease that causes skin and lung damage can be treated effectively by stem cell transplant, a new study in the New England Journal of Medicine has found. The approach could represent the first new treatment ...

A repurposed drug could open door to more stem cell transplants

December 20, 2017
A medication used to treat joint and skin conditions might also help people whose only hope of surviving cancer is receiving stem cells from a donor, according to research by a University of British Columbia scientist.

Pioneering stem cell gene therapy cures infants with bubble baby disease

March 28, 2017
UCLA researchers have developed a stem cell gene therapy cure for babies born with adenosine deaminase-deficient severe combined immunodeficiency, a rare and life-threatening condition that can be fatal within the first year ...

Stem cell transplant can grow new immune system in certain mice

November 22, 2007
Researchers at the Stanford University School of Medicine have taken a small but significant step, in mouse studies, toward the goal of transplanting adult stem cells to create a new immune system for people with autoimmune ...

Purified blood stem cells improve success of bone marrow transplants in mice, study shows

August 2, 2010
Researchers at the Stanford University School of Medicine have challenged decades of accepted wisdom about bone marrow transplantation with a new study showing that mice receiving purified blood stem cells are less prone ...

Recommended for you

Gene plays critical role in noise-induced deafness

October 19, 2018
In experiments using mice, a team of UC San Francisco researchers has discovered a gene that plays an essential role in noise-induced deafness. Remarkably, by administering an experimental chemical—identified in a separate ...

Functional engineered oesophagus could pave way for clinical trials 

October 18, 2018
The world's first functional oesophagus engineered from stem cells has been grown and successfully transplanted into mice, as part of a pioneering new study led by UCL.

New findings cast light on lymphatic system, key player in human health

October 16, 2018
Scientists at the Oklahoma Medical Research Foundation have broken new ground in understanding how the lymphatic system works, potentially opening the door for future therapies.

New model suggests cuffless, non-invasive blood pressure monitoring possible using pulse waves

October 16, 2018
A large team of researchers from several institutions in China and the U.S. has developed a model that suggests it should be possible to create a cuffless, non-invasive blood pressure monitor based on measuring pulse waves. ...

Age-related increase in estrogen may cause common men's hernia

October 16, 2018
An age-related increase in estrogen may be the culprit behind inguinal hernias, a condition common among elderly men that often requires corrective surgery, according to a Northwestern Medicine study was published Oct. 15 ...

Income and wealth affect the mental health of Australians, study shows

October 16, 2018
Australians who have higher incomes and greater wealth are more likely to experience better mental health throughout their lives, new research led by the Bankwest Curtin Economics Centre has found.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.