Gene Therapy for Immunodeficiency

November 19th, 2010

Well this post certainly doesn’t apply to most of our Southern Oregon allergy, asthma, and immunology population, but I can’t resist the urge to post comments about an article in this week’s issue of The New England Journal of Medicine:

Although gene therapy is not a new concept, its applications have been limited to a few rare and unique diseases thus far. Gene therapy for severe combined immunodeficiency (SCID) began over 7 years ago, but was unfortunately complicated by hematologic malignancy. As the vector (delivery of the gene of interest) technology has improved, additional strategies have emerged. The NEJM article reports 2 toddler boys with Wiscott-Aldrich syndrome (an immunodeficiency) who were successfully treated with autologous stem cells in which a functional version of their deficient gene was inserted using a viral vector. Essentially, their blood was drawn; appropriate stem cells were identified; these cells were infected with a virus in the lab, and the virus “inserted” the functional gene into a significant proportion of the cells; the patients’ own stem cells were re-infused and populated the bone marrow; these populations then reproduced.

Although long-term follow up of these boys will be important before we can hail this as a successfull application of gene therapy, these preliminary results look very exciting.

Immunodeficiency is the first disease model in which gene therapy has been applied successfully. In the future, we may see additional applications, including neurologic conditions (i.e. spinal cord injury, Alzheimer’s disease), endocrine problems (i.e. Type I diabetes), cardiovascular disease (secondary prevention for heart attack and stroke), and other respiratory diseases (such as cystic fibrosis).

Kevin Parks MD

Sublingual immunotherapy

November 16th, 2010

Immunotherapy, or “allergy shots” have been used since 1911 in the United States as a treatment for allergies and asthma. This treatment modality has been fine tuned over the past 20 years based on long-term efficacy studies on high-dose protocols over 3-5 years treament duration. These data have been convincing, and national treatment guidelines reflect the quality of the evidence, as allergen-specific immunotherapy is well established in the NHLBI asthma treatment algorithm and ARIA guidelines for treatment of allergic rhinitis (hay fever). Similarly definitive benefit has been demonstrated for allergen specific immunotherapy for hymenoptera (stinging insect) allergy.
In the United States, the sole route of allergen administration approved by the FDA is sub-cutaneous immunotherapy (SCIT). Over the past 20 years, mounting evidence supports the use of sub-lingual immunotherapy (SLIT) for select patients with allergies and/or asthma. The majority of currently available data on SLIT come from European studies using monotherapy with one allergen, such as grass, birch, or house dust mite. We still don’t have significant data on polysensitized individuals who desire SLIT. In Europe, it appears that the majority of polysensitized patients are still receiving SCIT based on the paucity of data on multiple-allergen SLIT.
What do we know about SLIT?
SLIT has an excellent safety profile, and is typically administered at home for this reason. Nuisance symptoms are common, including oral itching, throat itching, and occasional gastrointestinal distress. Severe side effects including anaphylaxis and severe oral ulceration have been reported, but are much less common. The cost of SLIT is likely to exceed the cost of SCIT, even if approved in the US, due to differential sensitization patterns among Americans compared to Europeans (we tend to have multiple allergies in this country), though cost comparisons are not yet widely available. At this time, any SLIT administered in the US is considered “off label”, dosed with antigens designed for sub-cutaneous use. This presents problems with coverage by insurers, as medical providers must justify such procedures using codes that describe the therapeutic indication and dosing. We also see potentially negative medicolegal implications with this use of antigens designed for sub-cutaneous use. The cost of SLIT in the US is currently born primarily by patients as “out of pocket” based on a recent survey of board-certified US allergists. Due to these obstacles, 94% of allergists in the US are not currently providing SLIT.
Will SLIT become more widely available in the US?
The answer is almost definitely “yes”. The data are certainly compelling for monosensitized patients. When we have approval from the FDA, legal and insurance obstacles will be largely overcome and many allergists, including AAC of Southern Oregon, will offer this option to appropriate patients. Polysensitized individuals (many allergies) will likely attain better results at reduced cost with SCIT, but monosensitized patients may find home SLIT (i.e. to grass pollen alone) to be a convenient and effective option. Of course, this decision should be individualized via discussion between the individual and the providing allergist.
At present, we are discussing this option with appropriate patients as a soon-to-become-available treatment modality. At our center, we have participated in studies evaluating the efficacy of SLIT for allergic rhinitis and asthma. Our experience has been positive thus far, and we look forward to additional data as they emerge.
Kevin Parks MD