Archives for April 2008

Gene therapy has been used to restrore sight

For the first time in humans, gene therapy has been used to restrore sight. The study, at the University of Pennsylvania, was designed to test the safety of the procedure, but the results were much better than anticipated.


The treatment was applied to two patients suffering from Leber’s Congenital Amaurosis (LGA), a rare congenital condition in which the patient’s have severely reduced vision due to the lack of the RPE65 gene, a retinal pigament epithelium specific protein, which is required for the maintenance of the epithelial cells covering photoreceptor cells in the retina.


Estimates showed that light levels after 90 days were increased by a factor of almost 5 orders of magnitude compared to the pre-treated state.


However, this is a treatment for just one type of LGA, which is merely one of many forms of blindness, the causes of which are often much more comlicated in terms of their etiology compared with the current study. Nevertheless, this study demonstrates the applicability of gene therapy as a paradigm to the treatment of both congenital and degenerative forms of blindness.


Nick Rhodes

Composition of Armed Forces Institute of Regenerative Medicine

The composition of the Armed Forces Institute of Regenerative Medicine (AFIRM) has just been announced by the US Department of Defense (DoD).  Unusually, the US Army Institute for Surgical Research at San Antonio in Texas will collaborate heavily with two civilian consortia in a quarter of a billion dollar initiative to accelerate the development of regenerative technologies for treating wounded soldiers.  This has been described as the largest ever federal investment in tissue engineering and regenerative medicine.


 The initial five year programme will develop technologies in the following areas:

  • Craniofacial repair
  • Non-scarring wound repair
  • Reconstruction following burns
  • Limb reconstruction, regeneration or transplantation
  • Compartment syndrome


Of the total, only one third will be provided from military budgets, and that will be shared between the US Army Medical Research Material Command, the Office of Naval Research, the National Institutes of Health, the Air Force Office of the Surgeon General and the Department of Veterans Affairs.


The two civilian consortia are led by the Wake Forest Institute for Regenerative Medicine with the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, and Rutgers University with the Cleveland Clinic.  Of note is the inclusion of UK-based tissue engineering company Intercytex established in Manchester in the development of skin.


Nick Rhodes

Brain Degeneration has been Cured with Therapeutic Cloning

Degenerative conditions of the brain are generally considered incurable, including Alzheimer’s and Parkinsons disease.  There have been limited attempts at curing neuronal degeneration, specifically in Parkinson’s, using embryonic stem cell implantation, notably in humans by Curt Freed of the University of Colorado Health Sciences Center, and in mice by Ron McKay of the US National Institute of Neurological Disorders and Stroke in Bethesda, Maryland.  The procedure is highly controversial due to the requirement for tissues from human embryos, each treament requiring approximately two individual foetuses.  Therapeutic cloning of reprogrammed cells has been proposed as a more ethical acceptable alternative, but there have been no reports of a successful demonstration of this.  Additionally, allogeneic cell therapy requires immune system suppression to allow the grafts to survive.


Lorenz Studer of the Sloan-Kettering Institute in New York, however, has successfully lead an international collaboration in implanting autologous skin cells that were reprogrammed into neurons and expanded in vitro, consequently restoring normal brain function in mice that were expressing degeneration similar to Parkinson’s disease.  This is the first time that brain degeneration has been cured with therapeutic cloning.  It is too early to predict if the same concept can be applied in humans.


In order to perform the research Lorenz Studer had to develop a method of imitating Parkinson’s disease, as the condition doesn’t occur naturally in mice.  To do this, they administered drugs which killed the dopamine-producing brain cells.


Embryonic stem cells were produced from skin cells of the mice tails in Wakayama’s labs in Kobe, Japan.  This was done using the standard procedure for mammalian cloning, where the donor cell nucei are implanted in eggs fron which the chromosomes have been removed, and embryos created from whcih embryoinic cells can be extracted.  These were then differentiated into dopamine-secreting neurons.  The advantage, compared to previous experiments, is that no immune suppression is required as the donor and recipient cells are genetically identical.


The form of cloning described in Studer’s experiments has not been achieved in humans, but would, in any case require a supply of human eggs.  However, of more scientific and technical interest would be the application of Yamanaka’s techniques of fibroblastic genetic reprogramming, where terminally differentiated cells can be reprogrammed into embryonic-like cells.  Much technical work is required before this could be applied in humans, but is promising enough to have many labs abandoning research on pure embryonic stems cells, including the Roslin Institute, who were first to clone a mammal.


Nick Rhodes

Embryonic Stem Cell Patent is to be Reinstated

Although Martin Evans, from Cardiff University, has been attributed with the key discovery of embryonic stem cells (ESCs) in the 1980s, and from which he received a knighthood in 2008, it was only in 1998 that they were actually first isolated from primates.  This step was finally achieved by James Thomson of the University of Wisconsin-Madison, using methods which he protected using three US patents. These have been highly controversial, and were revoked in 2007, following allegations in 2006 that the discoveries were highly derivative of work already published on the isolation of embryonic stem cells in other species.  In addition, the complainants alleged that the the Wisconsin Alumni Research Foundation, ultimate beneficiaries of the patents, had imposed unfair restrictions on use of the cells and were charging unreasonable licensing fees.


The US Patent and Trademark Office have, however, just announced that a single embryonic stem cell patent is to be reinstated.  Just one patent of the three, which protects the intellectual property (IP) regarding embryonic stem cells derived from pre-implantation human embryos, will again be available for protection.  Nevertheless, the original challengers of the patents have declared that they wil appeal this reinstatement, even though the new patenting arrangements will be less limiting to research with embryonic stem cells than was originally the case.


Nick Rhodes