Gene therapy and its uses

In treating SCID-X1

Severe Combined Immunodeficiency Syndrome

Hollywood’s Take:

Severe Combined Immunodeficiency Syndrome

David Vetter (1971-1984)

SCID-X1 Most Common Type of Severe Combined Immunodeficiency Syndrome Between 1:50,000 and 1:100,000 children are born with a SCID Accounts for over 50% of cases

Sex-linked – gene is carried on the X-chromosome

It is a recessive trait

SCID-X1 Results from damage to gene coding for γ common (γc) cytokine receptor γ c cytokine is necessary for many interleukins to function Defective cytokine dependent survival signaling in

T and NK leukocytesThis results in complete lack of T and NK cells, leading to total breakdown of immune system.

SCID-X1Clinical Symptoms:

Early onset lung and digestive tract

infections

Infection by parasites

Failure to thrive

Without proper treatment,

children born with SCID-X1 will die before their first

birthday.

Gene Therapy Gene therapy opens up an exciting world of possibilities for patients with SCID-X1. No waiting for a matched Hematopoietic Stem Cell (HSC) donor Less chance of rejection

Adenoviral Vectors

Adenoviral Vectors Contains DNA Chosen for non-mitotic cells Viral DNA is inserted into nucleus, but is never

incorporated into host cell’s chromosomes Viral DNA can undergo transcription, but not replication in the cell. Transient expression of desired protein No risk of oncogenic side effects

http://rufusrajadurai.wetpaint.com/page/AIDS-Acquired+Immuno+Deficiency+Syndrome

1:47-3:02

Retroviral Vectors Used on mitotically active cells (such as HSC’s) Enter cell by same method Contain RNA instead of DNA Incorporate their genetic material into the host cell’s genome via reverse transcriptase and integrase Therapeutic DNA can be replicated along with cell’s DNA Danger of disrupting existing genes (LMO2)

Clinical Studies•Marina Cavazzano-Cavalo and Alain Fischer were first to achieve successful gene therapy for SCID-X1 in 2000. •They did so using a retroviral vector•They did not use any immunosuppressive drugs in their treatment•First two study patients saw presence of lymphocytes and immunoglobulin levels approaching normal ranges for their age cohort in as little as nine months.

Clinical Studies•Between early studies in France and Britain, it was shown that out of a total of 20 cases, all but 2 individuals saw increased lymphocyte count following gene therapy, but even the two who didn’t showed clinical signs of better overall health.

•A follow-up study performed in the United States showed that effectiveness of gene therapy as a viable treatment option for SCID-X1 patients decreased with patients’ age.

ConclusionGene therapy gives us an exciting new way to look at treating many diseases,

including severe combined immunodeficiencies. While the overall

technology still has some kinks to work out, the benefits of gene therapy

far outweigh the risks.