A novel form of gene therapy has been successfully trialed on five patients with X-linked severe combined immunodeficiency (SCID-X1), a genetic disorder characterized by the inability to produce certain types of white blood cells. The condition is thought to affect one in 50,000 to 100,000 people, many of whom do not live beyond infancy if left untreated.
SCID-X1 is produced by a mutation of a gene called IL2RG, which is located on the X chromosome. Since males have only one X chromosome, they only require one mutated form of the gene in order to develop the condition, whereas females, who have two X chromosomes, won't suffer from SCID-X1 unless both of their IL2RG genes are altered. Consequently, the disorder is significantly more prevalent in males than females.
IL2RG is responsible for coding certain proteins involved in the formation and growth of lymphocytes, white blood cells that help attack and destroy harmful viruses and bacteria that have entered the body. However, when the gene does not work properly, this vital immune response is disabled, meaning sufferers of SCID-X1 are unable to fight off infections and are therefore highly susceptible to a range of diseases.
Currently, the condition is treated by replacing the sufferer's immune system with that of a healthy donor, via a bone marrow transplant. However, with this technique yielding mixed results, a team of researchers at the National Institute of Allergy and Infectious Diseases sought to develop a new form of treatment by genetically modifying patients' own immune cells.
To do so, they removed stem cells from participants' bone marrow, and used a type of virus called a lentivirus to introduce a non-faulty IL2RG gene into these cells. The gene-corrected stem cells were then re-introduced into the patients' blood, where researchers hope they will enable the production of healthy immune cells over a long period of time. In order to test this, the team will continue to monitor the immune systems of the participants for up to 15 years.
The first two patients to receive the treatment began the process three years ago. While both displayed substantial improvements in their immunity, one unfortunately died due to pre-existing lung damage, caused by an infection which the body was unable to fight off prior to undergoing gene-correction therapy. The other original subject continues to show improvements, while the final three participants were all treated in the past three to six months, with positive reactions.
A full account of the study is set to be presented by Dr. Suk See De Ravin at the 57th American Society of Hematology Annual Meeting, which is currently taking place in Orlando, Florida.
