Tag Archives: anna Matynia

Advancing gene therapy, debunking AR propaganda.

The promise of curing genetic diseases by replacing damaged genes with healthy ones is slowly becoming a reality. One recent story is the development of therapy in humans to reverse a form of childhood blindness called Leber congenital amaurosis, or LCA.

OregonLive reports on the story of Alexe Webb who, soon after birth, was diagnosed with LCA the most common cause of inherited blindness in children. Her doctor, Dr. Richard Weleber, said “With this trial, she has the opportunity to have much better vision. We hope the treatment is very durable, that it will last for many decades, even for life.”

As detailed at the National Eye Institute web site:

The groundbreaking clinical trials to restore vision in patients with LCA rest on 15 years of basic research with animals. Long before the gene transfer procedure could be tested in people, four critical milestones had to be met: the discovery of the RPE65 gene; creation of a mouse model that illustrates the gene’s functions and what happens when it’s missing; development of a safe way to carry healthy replacement genes to the target within the eye; and studies of the procedure in a large animal model — dogs.”


The report continues:

Dogs carrying a nearly identical mutation to Alexe’s were the first test subjects. Within two weeks of treatment, three nearly blind dogs were able to navigate with little problem, Dr. Jean Bennett, a professor of ophthalmology at the University of Pennsylvania Medical School in Philadelphia told the Journal of the American Medical Association in October. The effects of a single injection persisted for more than 10 years in the first dog treated. Researchers learned that retinal cells may be ideal targets for gene therapy because they don’t divide much, allowing replaced genes to persist.”


This isn’t the first time that this use of gene therapy to treat LCA has caught our attention, back in 2009 Anna Matynia wrote a piece which highlighted the value of the briard dog to this research. All in all it is a great example of how gene therapy is starting to change the face of medicine.

The briard dog, crucial to the development of gene therapy for LCA

In other news we reported last week on how the animal rights zealots at PCRM were willing to endanger the lives of preterm babies by attacking an important training program at the University of Washington.  We were pleased to note an editorial in the Seattle Times which comes down firmly on the side of the University of Washington, the Seattle Times clearly recognizes that Dr. Dennis Maycock and his colleagues at the University of Washington are the real responsible and ethical physicians in this debate.

The problem of specialist pediatric training programs coming under attack from AR activists is not however limited to Seattle, PeTA are attempting to close down a similar training program at Primary Children’s Medical Center (PCMC) in Salt Lake City. The Daily Herald has reported how PeTA have resorted to false claims that PCMC have conceded to their demands. Once again doctors have had to confront misleading animal rights propaganda, with Dr. Bonnie Midget of PCMC pointing out that:

There is no simulator for a 2-pound premature infant,We would love it if someone would make one.”


We at Speaking of Research applaud the responsible physicians at the University of Washington and PCMC who brave threats and harassment to stand up for the welfare of their youngest patients.

Dario Ringach and Paul Browne

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

Gene therapy for blindness – when dogged determination pays off!

Leber’s congenital amaurosis is a progressive disorder that affects about 3,000 Americans, and hundreds of thousands worldwide, and causes a progressive loss of vision that usually results in blindness. The disease, for which there has until now been no effective treatment, is caused by a mutation in the encoding RPE65, an enzyme which is crucial to the production of the chemical 11-cis retinal that photoreceptor cells in the eye need so that they can respond to light.

In one of my first posts for Speaking of Research last year I discussed on this blog how two teams of scientists at Moorfields hospital in the UK and the University of Pennsylvania had used gene therapy to introduce a functioning RPE65 gene into the eye of patients with Leber’s congenital amaurosis, and only last month Anna Matynia discussed how this treatment employs adenovirus-based vectors that have been developed through years of research in rodents and dogs. While the results of those trials were promising the benefits to most of the patients were modest, which was not all that surprising since the scientists doing the trials knew from their studies of Briard dogs with naturally occurring mutations in the RPE65 gene that the therapy needed to begin early in the course of the disease for maximum benefit. For this reason, and because the therapy appeared safe in the first adult human trials, the team at Pennsylvania decided to include children with Leber’s congenital amaurosis in their next study group.


Briard Dog

The early results of that study have been announced following publication in the medical journal The Lancet, and as expected the greatest benefits have been seen in the children, one of whose eyesight improved to nearly normal, though adults in the study also experienced significant improvement. While this particular therapy will benefit a relatively small number of patients its success and that of early trials of gene therapy for Parkinson’s disease are an indication how gene therapy, a field of medicine that has seen its fair share of hope and disappointment over the past couple of decades, is maturing as scientists have learned from both animal studies and human trials about how to harness this powerful therapeutic approach.

The insights gained through the study of the Briard dog with naturally occurring mutations in the RPE65 gene are a good example of the increasingly close ties between clinical and veterinary medicine, a collaboration that is exemplified by the Comparative Oncology Trials Program which brings together veterinary and clinical oncologists under the leadership of the National Cancer Institute to study cancers that affects both dogs and humans, with a dozen trails of new anti-cancer medications already underway. In the future such trials may play an important role bridging the gap between in vitro and rodent studies in the lab that rely on a relatively limited range of cancer cell lines and the far more diverse cancers seen in the clinic. It is hardly surprising that antivivisectionist groups are opposed to these trials, as our colleagues at Understanding Animal Research point out they are quite happy to put dogma ahead of dogs, but fortunately the majority of veterinarians have a much more positive attitude to animal research.


Paul Browne