David Vetter, popularly known as the “boy in the bubble”, was born with Severe Combined Immune Deficiency (SCID). As one of the most severe cases of primary immunodeficiency, SCID impairs the growth and operation of immune cells that protect against infection. Although seemingly healthy initially, infants born with SCID are at heightened risk of severe infections and usually do not survive beyond two years of age without treatment. These infants may experience frequent infections, particularly viral ones, which can lead to serious conditions like pneumonia and chronic diarrhea. Additionally, yeast infections in the mouth and diaper area are common indicators of SCID. Despite seeming healthy when he was born, David had to be kept in a sterile environment to avoid exposure to germs. Otherwise, he risked developing various severe illnesses.
Hematopoietic Stem Cell Transplantation (HSCT) is the standard form of treatment for infants with SCID, which often only partially restores immunity. When David was born in 1971, the sole treatment available for SCID was a bone marrow transplant. This procedure involved replacing the compromised immune system with a healthy one by providing a source of hematopoietic stem cells (HSCs). This is achievable because HSCs are robust blood-forming cells capable of maturing into various types of immune cells, contributing to the establishment of the immune system. Unfortunately for David and his family, despite receiving a bone marrow transplant he tragically succumbed to lymphoma, a cancer originating from abnormal white blood cells in the lymph glands, just four months after receiving the bone marrow transfusion.
SCID is one of the many diseases that is a result of inborn abnormalities of immunity. Monogenic immune system abnormalities, referred to as inborn errors of immunity (IEI), are mutations in single genes that result in specific impairment to the normal development and function of the immune system. IEI can lead to various health issues such as increased vulnerability to infections, problems with the immune system, inflammation within the body, autoimmune conditions, allergies, and even certain types of cancers. Although rare, the aggregated number of individuals with an IEI represents a significant health burden.
In the 1970s, scientists made significant strides in understanding genetic diseases and how genes work. This led to the development of genomic cell modification as a potential treatment approach. Thanks to progress in virology, researchers figured out how to create vectors, which are delivery vehicles that carry healthy copies of genes into cells. This technology showed promise as a treatment for people with IEI. One of the first successes was in treating SCID using gene therapy. This breakthrough led to further research, particularly with lentivirus-based vectors, to address other types of IEI through gene transfer.
The development of safe and effective gene therapy techniques throughout the previous 25 years has resulted in long-term clinical benefits in four IEI’s: SCID-X1, ADA SCID, WAS (Wiskott-Aldrich syndrome), and CGD (chronic granulomatous disorders). Researchers have made significant scientific and technological strides, enhancing the effectiveness and safety of treatments for IEIs. Traditional HSCT has advanced, leading to higher cure rates for IEIs, allowing researchers to compare gene therapy’s new approach with HSCT.
Overall, the steady advancement of science and technology has greatly enhanced the efficacy of both traditional HSCT and gene therapy in treating IEIs. Through the study of these conditions, researchers have gained invaluable insights into immunology, driving ongoing improvements in therapeutic strategies. As our understanding continues to deepen, we can anticipate further progress in the treatment and management of immune-related disorders, offering hope for better outcomes and quality of life for those affected by IEIs.
Jennifer Sahadeo
