Stem cells offers hope in the ‘bubble boy disease’ treatment

Researchers from Salk Institute for Biological Studies, USA have developed a method of treatment of severe combined immunodeficiency with stem cells. The results are published March 12, 2015 in the journal Cell Stem Cell.

For children with severe combined immunodeficiency (SCID), also known as “bubble boy” or “bubble baby” disease, even the common cold can be deadly. They often have to live in sterile, isolated environments to avoid infections. But even in such conditions, the majority of patients do not live more than one or two years.

In some cases, early bone marrow transplantation before contamination help kids with SCID successfully grow up, go to school and lead a practically normal life.

However, previous attempts to treat SCID using bone marrow transplantation or gene therapy showed conflicting results. In the 1990s, began a clinical trial that considered to be very effective. With the help of viruses which deliver the needed genes to newly growing cells in the patient’s bone marrow. While this gene therapy did cure the disease at first, the artificial addition of genes ended up causing leukemia in a few of the patients.

The SCID disease is caused by mutations of bone marrow stem cells, in result a defect in the production and/or function of both B-lymphocytes and T-lymphocytes, responsible for immunity.

Researchers at the Salk Institute have found a way to genetically “edit” in laboratory conditions stem cells which derived from “bubble boy” cells, and then return them to the owner, making the immune system.
For new method of SCID treatment, consisting of three phases, a team from the Salk Institute used bone marrow samples of the deceased patient from Australia.

In the first phase, scientists reprogrammed cells into induced pluripotent stem cells (iPS cells), similar to the properties of embryonic stem cells (ESCs). ESCs can turn in almost any cell type of the body and have significant potential for regenerative medicine.

In the second phase was used a new method of editing the genetic defects that cause severe combined immunodeficiency. To correct a mutation, researchers used a technique TALEN (Transcription Activator-Like Effector Nuclease). Using a set of enzymes working on the similarity of molecular scissors, scientists cut out the ‘faulty’ DNA base pairs, replacing them with others.

“In contrast to traditional methods of gene therapy, we added completely new gene into the DNA of a patient, which might cause undesirable side effects. We use a method TALEN, changing only one nucleotide in a gene to fix mutation”, – said one of the leading collaborators study, Dr. Tushar Menon.

In the third step iPSCs were stimulated to differentiate into vital cells of the immune system. This is not an easy process, that can be done in stages to unlimited number of cell transplantation to patient.
To achieve the required result, researchers in collaboration with scientists from the University of California at Los Angeles have created an environment based on specially selected nutrients and growth factors. After some time, “Corrected” iPSCs turned into mature NK-cells.

Currently the team is working on the reproduction of other vital components of the immune – T-cells. Scientists were able to make iPS cells transform into precursors of T-cells, but further development in the mature form was not available yet.

“Our work demonstrates a new method of treatment of this devastating disease – a more effective and less invasive. The method also has the potential to create a therapy for other deadly and rare diseases of the blood”- said study leader Professor Inder Verma.

David Vetter (1971-1984) - The world famous

David Vetter (1971-1984) – The world famous “bubble boy”