Re: First Demonstration of Apparently Fully Curative Gene Therapy

[Guest guest]

Wow, I can only imagine how this must feel to the parents of these

kids, not to mention the kids themselves.

Debi

>

> First Demonstration of " Apparently Fully Curative " Gene Therapy

>

> Zosia Chustecka

>

> Medscape Medical News 2006. © 2006 Medscape

>

> http://www.medscape.com/viewarticle/549132_print

>

> December 11, 2006 (Orlando) — Success with gene therapy in infants

> with severe combined immunodeficiency (SCID) reported at the American

> Society of Hematology (ASH) 48th Annual Meeting and Exposition spells

> " good news for the whole field of gene therapy, " say the researchers.

>

> The results come from a trial of 8 children (aged 7 months to 5.5

> years) with SCID caused by a defective gene for adenosine deaminase

> (ADA). These infants are so immunocompromised that any infection is

> potentially life threatening, and they often spend their short lives

> encased in a plastic " bubble. " They were treated with transduced

> autologous hematopoietic stem cells transfected with the ADA gene,

> inserted via retroviral-mediated transfer.

>

> " All of the children are currently healthy and thriving, " lead

> researcher Alessandro Aiuti, MD, from the San Raffaele Telethon

> Institute for Gene Therapy, in Milan, Italy, told the meeting. " They

> are living normal lives and are going to school and kindergarten. "

> They have shown no adverse events related to the gene transfer, and

> none have developed severe infections.

>

> All of the infants with longer follow-up who have a completely

> reconstituted immune system do not require any treatment, so it

> appears that the gene therapy is " curative, " Dr. Aiuti told Medscape.

> However, this reconstitution takes time, and before the process is

> completed, patients are given immunoglobulins, he added. Before entry

> into the trial, 6 of 8 children were on ADA enzyme-replacement therapy.

>

> " This is the first demonstration of an apparently fully curative

> gene-therapy transplant, " Emerson, MD, PhD, from the

> University of Pennsylvania, in Philadelphia, told Medscape. These

> children have gone from " bubble to playground, " he said.

>

> Speaking as the moderator of an ASH press conference at which this

> trial was highlighted, Dr. Emerson said the results are good news for

> the whole field of gene therapy. " In this trial, the gene therapy

> offered tremendous benefits with no toxicity, and it offers real

> promise for the future for the potential of gene therapy in more

> common and more complex diseases, such as sickle-cell anemia and

> thalassemia. "

>

> Also speaking at the press conference, Dr Aiuti explained that

> previous attempts at gene therapy for ADA-SCID have not been totally

> successful, as the children continued to need enzyme-replacement

> therapy (with pegylated ADA). One of the innovations in their own

> protocol was the use of the cytoxic agent busulfan, which helps the

> engraftment process by " making room for the new stem cells, " he

> commented. Busulfan was administered at 2 mg/kg per day on days 3 and

> 2 prior to the transplant and resulted in a transient myelosuppression

> in most patients, although in 2 patients this myelosuppression was

> prolonged. " It appears that the greater the extent of neutropenia, the

> better the engraftment, " Dr Aiuti commented.

>

> It appears that the gene therapy results in persistent gene

> correction, Dr. Aiuti commented. Long-term engraftment of the

> transduced cells was demonstrated by stable multilineage marking:

> T-cell counts were normal, and there was a restoration of T-cell

> function. There were also metabolic benefits — the children did not

> need treatment with pegylated ADA enzyme replacement, and 7 of 8

> patients showed an increase in both height and weight. " The 1 patient

> who didn't was treated at an older age, so there was probably more

> damage there, " Dr. Aiuti said.

>

> The median follow-up is 3 years, and the longest is 6 years, but there

> is real hope that the effects will " last for a lifetime, " he said.

>

> Dr. Aiuti and colleagues are continuing with this approach and have so

> far treated 1 other patient. They concluded that the data so far

> " confirm the safety and the efficacy of gene therapy in improving

> immune and metabolic function in children diagnosed with ADA-SCID " and

> suggested that this approach " may represent a viable solution to

> reduce the mortality rates associated with SCID in newborns. "

>

> ASH 48th Annual Meeting and Exposition: Abstract 200. Presented

> December 11, 2006.

>