It may be possible to implant the tweaked stem cells back into an SCID patient.
Image credit: Salk Institute
Severe combined immunodeficiency disease (SCID) - once referred to as "bubble boy disease" - is a group of rare, life-threatening disorders caused by gene defects that prevent bone marrow from making key immune cells called T and Natural Killer (NK) cells.
According to the Centers for Disease Control and Prevention (CDC), the annual incidence of SCID is 1 case per 40,000-100,000 live births, or around 40-100 new cases among babies in the US every year.
Children with SCID cannot fight off even the mildest of germs; even an ear infection can kill them.
They often have to live in isolated, sterile environments, and many die before their second birthday.
In some cases, if treated before infection sets in and bone marrow transplant is successful, children with SCID can grow up, go to school, and for the most part lead nearly normal lives.
Healthy NK immune cells grown from SCID patient-derived stem cells
In the journal Cell Stem Cell, researchers from the Salk Institute for Biological Studies in La Jolla, CA, describe how for the first time, they grew healthy NK immune cells in the lab from gene-edited stem cells derived from the cells of an SCID patient.
While it is still in the preliminary stage, they believe their technique offers the possibility of implanting the "tweaked cells" back into a patient so they can generate a complete immune system.
Such an option would be a huge leap forward. There is currently no cure for SCID, and current treatments - which rely on bone marrow transplants or gene therapy - do not always work.
Senior author Inder Verma, Salk professor and American Cancer Society professor of molecular biology, says:
"This work demonstrates a new method that could lead to a more effective and less invasive treatment for this devastating disease. It also has the potential to lay the foundation to cure other deadly and rare blood disorders."
Gene therapy held great promise for the treatment of SCID. This method, trialed in the 1990s, used bits of virus to deliver the correct genes to cells growing in the patient's bone marrow.
At first, this type of gene therapy seemed to work, but the way the genes were added eventually caused leukemia in some patients.
Since then, other gene therapy methods based on bone marrow transplants have been developed and are effective, but usually only in patients with mild forms of SCID. It is also a very difficult operation to carry out on very sick babies.
Team used new gene-editing technology to correct single fault in gene
For their study, the team focused on X-linked severe combined immunodeficiency or X-SCID - a form of the disease that results in a very poorly functioning immune system.
They generated stem cells from the cells of a deceased Australian patient with X-SCID, and used a very precise technique to make just one correction to the faulty gene in the stem cells, before coaxing them to grow new, healthy immune NK cells.
The process they devised consists of three stages: reversion of the patient's cells into induced pluripotent stem cells (iPSCs), use of new gene-editing technology to correct the genetic fault in the iPSCs, and - with the help of a concoction of nutrients and other factors - prompting the iPSCs to generate NK cells.
The iPSCs are like embryonic stem cells. They have the ability to transform into any type of tissue cell and hold great promise for regenerative medicine.
The gene-editing technology the researchers used - called TALEN - uses enzymes that work like molecular scissors to snip away at a gene and replace individual "letters" in the DNA code to correct the mutation.
Prompting the gene-edited iPSCs to generate the necessary immune cells is not an easy process, say the authors, but it has the potential, if done in stages, to allow an unlimited supply to be transplanted back into the patient.
First author and Salk postdoctoral researcher Dr.Tushar Menon explains the attraction of their approach:
"Unlike traditional gene therapy methods, we aren't putting a whole new gene into a patient, which can cause unwanted side effects. We use TALEN-based genome editing to change just one nucleotide in one gene to correct the deficiency. The technique is literally that precise."
In the following video, the team describes what they did in the study:
The researchers are now working on extending their technique to produce the other important missing component in X-SCID - vital immune T cells. They have managed to coax the iPSCs to turn into precursors of T cells but have not yet been able to bring them to maturity.
Some of the funds for the study came from Sanofi Aventis, Ipsen/Biomeasure, the Leona M. and Harry B. Helmsley Charitable Trust, the H.N. and Frances C. Berger Foundation and the California Institute for Regenerative Medicine.
In October 2014, Medical News Today reported how, using laboratory mice, researchers at Virginia Tech discovered a potential biomarker for a noninvasive newborn test for SCID that looks for a microbe in fecal matter.