Early clinical success for stem cell gene therapy in two diseases

A clinical trial of a gene therapy to treat children with two types of severe genetic disorders has shown early signs of success.

'The results obtained from the first six patients are very encouraging', said Professor Luigi Naldini, director of the San Raffaele Telethon Institute for Gene Therapy (TIGET) in Italy, who led the research. 'The therapy is not only safe, but also effective, and able to change the clinical history of these severe diseases'.

Two rare genetic diseases, metachromatic leukodystrophy (MLD) and Wiskott-Aldrich syndrome, were targeted in the trials. The diseases are caused by inherited gene mutations and affect patients in early childhood, with debilitating or even fatal effects.

Researchers used a new, harmless version of the HIV virus to deliver correct copies of the defective gene. They collected bone marrow cells from the patients and used the modified virus to carry the normal gene into those cells. The patient's defective bone marrow was then destroyed, and the modified cells were transplanted back into the patient to replace them.

Sixteen children have been treated in the clinical trials to date but only six children, three with each disease, have been followed for sufficient time to draw initial conclusions. The children with MLD received gene therapy before symptoms appeared and have so far developed no symptoms of the disease. Symptoms usually develop around the age of one. Children with Wiskott-Aldrich syndrome typically have progressively worsening health, but the children involved in the trial showed improvements in their symptoms.

The risk of tumours following gene therapy has been a problem seen when trialling other gene therapy techniques and has hampered progression in this field. However, the children in these trials were followed for up to two and a half years after treatment and have so far shown no signs of cancer.

'Until now we have never seen a way to engineer stem cells using gene therapy that is as effective and safe as this one', said Dr Eugenio Montini of TIGET, and a co-author of the studies. 'These results pave the way for new therapies for other more common diseases'.

MLD causes progressive neurodegeneration, resulting in paralysis and dementia. Few children survive beyond a few years after onset, and there is currently no other effective treatment available. Wiskott-Aldrich syndrome affects the immune system and children are at risk of recurrent infections, autoimmune diseases and cancer. Its progression can be halted by a bone-marrow transplant, if a suitable matched donor can be found, but life expectancy is low at 15-20 years.

'The results we're showing today…give us a great hope for the future of these children', said Professor Maria Grazia Roncarolo, scientific director of the San Raffaele Scientific Institute, who was also involved in the research.

'The field is slowly but surely making impressive advances against…quite untreatable diseases', Dr Theodore Friedmann, a paediatric gene therapist at UC San Diego who was not involved in these studies, told the LA Times.