X-linked SCID: What is the best treatment for “Bubble Boy” Disease?

bubbleX-linked Severe Combined Immunodeficiency (X-linked SCID) is the most common form of Severe Combined Immunodeficiency; a disorder of the immune system where the body produces very few T cells and Natural Killer (NK) cells. X-linked SCID patients are unable to mount effective antibody responses to antigens they may come into contact with.

 X-linked SCID is an extremely life-altering disease, which has in the past confined some patients to living in a sterile “bubble,”  to avoid contact with pathogens which they would be unable to fight off. This was famously demonstrated by the life of David Vetter, an X-linked SCID sufferer who lived in a sterile chamber – coined by the media as his “bubble” – for all his life. He died in 1984 at age 12 following a bone marrow transplant.

The disease is caused by a recessive mutation, and occurs almost exclusively in males because they have only one X-chromosome. Females have two X-chromosomes, and are very unlikely to have the defective gene on both. The mutation is in a gene called IL2RG, which encodes the “common gamma chain” (γc), a component of many cytokine receptors; IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21.

As the γc chain is required for a number of cytokine receptors, patients with X-linked SCID have defective cytokine signalling. IL-7 (and therefore the IL-7 receptor) and IL-15 (and therefore the IL-15 receptor) are essential for early T lymphocyte and Natural Killer cell development, respectively. Consequently, T and NK cells are profoundly defective, and sufferers cannot mount antibody responses (which are dependent on T cells) or cell-mediated immunity such as cytotoxic T cell killing. As a result, X-linked SCID sufferers are highly susceptible to pathogens, and commonly die in early childhood without treatment.

For most SCID patients, bone marrow transplants are the optimal treatment for the disease. This allows the patient’s abnormal immune cells to be replaced with healthy cells from the bone marrow donation. Ideal donors are HLA (Human Leukocyte Antigen)-identical relations such as a sibling, but it is possible to obtain a bone marrow transplant from a parent or HLA-matched unrelated donor.  Although bone marrow transplantation can be a successful treatment for X-linked SCID, there is a serious risk of developing Graft-versus-Host Disease (GVHD), a complication which can be fatal. Additionally, many patients do not have a suitable HLA-identical relation such as a sibling. Due to lower success rates of using non-HLA-identical bone marrow donors, bone marrow transplantation is not always a preferable treatment. In recent years, gene therapy as a treatment for X-linked SCID has been extensively researched and trialled, as an alternative to bone marrow transplants.

A clinical trial which began in Paris in 1999 illustrates the conflicting risks and benefits of gene therapy as a treatment for X-linked SCID. 10 infants with the disease took part in the study, where normal human γc chain cDNA was transferred into their bone marrow CD34+ cells using a retroviral vector (Cavazzana-Calvo et al, 2000). Initially, the results of the gene therapy were good, with the infants expressing the normal IL2RG gene in T, NK and B cells, and therefore producing the functional γc chain protein. However, over the following 5 years, four of the clinical trial patients developed a T cell leukaemia-like complication, which led to the death of one of the patients. During the gene therapy procedure, the retroviral vector was integrated near the first exon of the LMO2 gene. LMO2 encodes a protein involved in stem cell growth, which is not normally activated in T cells. Its inappropriate activation can cause spontaneous cases of T cell leukaemia; it is thought that the retroviral vector inserting the normal IL2RG gene may have “turned on” the LMO2 oncogene during its integration into the chromosome. This caused overexpression of the oncogene and lead to the leukaemia cases

The relative benefits and risks of both bone marrow transplantation and gene therapy have to be considered in order to determine the best treatment option for individual X-linked SCID patients. Gene therapy is now known to carry previously unforeseen risks such as the possibility of T cell leukaemia development. However, it has been shown to provide sustained clinical benefit to the majority of patients. Bone marrow transplantation is a more established treatment option, but carries risks of serious complications such as GVHD, as well as problems associated with many patients not having access to a HLA-identical donor. Treatment choice is dependent on a number of factors; access to identical bone marrow donors, as well as weighing up the associated risks of both bone marrow transplants and gene therapy. With X-linked SCID, patients do not live beyond childhood unless treated, so it is important to initiate therapy at a young age.


8 Responses to “X-linked SCID: What is the best treatment for “Bubble Boy” Disease?”

  1. treatment March 25, 2013 at 5:12 am #

    I think the admin of this website is actually working hard for
    his web page, since here every information is quality based

  2. toric contact lenses April 9, 2013 at 10:40 am #

    Good day! I could have sworn I’ve visited this web site before but after looking at a few of the posts I realized it’s new to me. Anyhow, I’m definitely happy I discovered it and I’ll be bookmarking it and checking back frequently!

  3. rising cities hack download April 20, 2013 at 4:25 pm #

    I got this website from my pal who shared with me regarding this website and now this time I am visiting
    this site and reading very informative content at this time.

  4. jfsuy.com June 4, 2013 at 2:16 am #

    You’ve made some really good points there. I looked on the web for more information about the issue and found most individuals will go along with your views on this web site.

  5. get free microsoft points offers June 7, 2013 at 3:34 am #

    hey there and thank you for your info – I’ve certainly picked up something new from right here. I did however expertise a few technical points using this site, as I experienced to reload the site many times previous to I could get it to load correctly. I had been wondering if your web hosting is OK? Not that I’m complaining,
    but slow loading instances times will very frequently affect your placement
    in google and can damage your quality score if advertising and marketing with Adwords.
    Well I’m adding this RSS to my e-mail and could look out for much more of your respective intriguing content. Ensure that you update this again very soon.

  6. This is the right webpage for anybody who wants to find out about this topic.
    You know a whole lot its almost tough to argue with you (not that I really would want to…HaHa).

    You definitely put a fresh spin on a subject which has been written about for
    ages. Great stuff, just wonderful!

  7. website August 27, 2013 at 1:37 am #

    Wonderful article! We are linking to this particularly great article on our site.
    Keep up the good writing.

  8. Versicherungsmakler Freiburg November 26, 2013 at 2:53 pm #

    Its such as you learn my mind! You seem to grasp so much approximately this,
    such as you wrote the ebook in it or something. I think that you just can
    do with some p.c. to pressure the message house a bit, however other than that, this is wonderful blog.
    A great read. I will certainly be back.

Leave a Reply