Breakthrough of the Year (almost!)

As the year draws to a close it’s time to reflect on an exciting year of animal research, and there seems no better place to start than with the top 10 breakthroughs of the year as selected by the prestigious scientific journal Science. Science is of course a general science magazine, and the choices reflect this with research in diverse fields ranging from astronomy to paleontology.

Last year our sister organization in the United Kingdom reported that Science had selected cell reprogramming to produce induced pluripotent stem cells (iPS cells) as their breakthrough of the year.  Since then we have reported how the safety of iPS technology continues to improve while others have discussed exciting research which shows just how powerful the technique is by reprogramming fibroblast cells to generate healthy mice that can themselves produce offspring.

This year the top slot went to the discovery and study of Ardi, a 4.4 million year old ape who promises to shed a great deal of light on early human evolution, though it remains to be seem if she and her kind are a direct ancestor of modern humans.

We did have the consolation that one of the nine runner ups is an area of medicine to which animal research has made an enormous contribution , the return of gene therapy with Science claiming that  this year “… gene therapy turned a corner, as researchers reported success in treating several devastating diseases”. These diseases include X-Linked adrenoleukodystrophy, a usually fatal disease of the brain and nervous system, Leber’s congenital amaurosis, an inherited eye disorder that leads to blindness, and severe combinedimmunodeficiency (SCID)due to a lack of an enzyme called adenosinedeaminase.

Only last month I wrote about the crucial role of research with mice in developing the gene therapy for X-Linked adrenoleukodystrophy, while both Anna Matynia and I have written about Leber’s congenital amaurosis.  However,  we have not yet had an opportunity to discuss the therapy developed for treating SCID  in patients whose immune system has collapsed because they lack an enzyme named adenosine deaminase (ADA) which is crucial for removing toxic metabolites from cells.

A clinical trial published in January by the New England Journal of Medicine (1) reported how an Italian team had successfully treated  children with SCID by harvesting bone marrow stem cells from the boys and treating these cells with a retroviral vector containing the ADA gene that produces adenosine deaminase, and then transplanting the modified cells back into them.  In 5 of the boys the therapy restored normal function and significant improvements in the function of the immune system were observed in the other 5.  This therapy has been a couple of decades in development and one of the key investigators involved in this effort, and indeed in the recent clinical trial,  has been Dr. Claudio Bordignon of the University of Milan. Dr. Bordignon developed techniques that enabled scientists to study the ability of retrovirus transformed bone marrow cells from patients with ADA-SCID  to restore immune function in  the NOD/SCID mice that lack a functioning immune system (2).  This enabled him and his team to develop retroviral vectors that could safely drive the production of adenosine deaminase in bone marrow stem cells that survived for long periods after transplantation and are suitable for use in ADA-SCID patients where they need to function for many years.

It’s great to see an area of medical research that we’ve been following closely over the past year receive this recognition from Science, and we hope that as with iPS cells in 2009 gene therapy continues to show what it can do in 2010.

Paul Browne

1)      Aiuti A. et al.”Gene therapy for immunodeficiency due to adenosine deaminase deficiency.” N Engl J Med. Volume 360(5), Pages 447-458 (2009) DOI:10.1056/NEJMoa0805817

2)      Ferrari G. et al “An in vivo model of somatic cell gene therapy for human severe combined immunodeficiency.” Science. Volume 251(4999), Pages 1363-1366 (1991) PubMed:1848369

One response to “Breakthrough of the Year (almost!)

  1. Here is a link to more information about the genetics of Adenosine Deaminase Deficiency that was prepared by our genetic counselor and which has links to some useful resources for those dealing with this condition: There is also a phone number listed if you need to speak to a genetic counselor by phone. I hope it helps. Thanks, AccessDNA