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In-Vivo Gene Therapy Technique to Cure XSCID in Basset Pups

l potential problems with this approach,’ said Peter J. Felsburg, professor of immunology at Penn's School of Veterinary Medicine. ‘The number of gene-corrected bone- marrow stem cells that can be transplanted back into the patient is limited to correcting the potentially low number of bone-marrow stem cells harvested from the patient. In addition, the manipulation and culturing of the cells outside the body may alter their ability to provide for long-term generation of new immune cells.’

The Penn researchers and their NIAID colleagues, led by Drs. Suk See Ting-De Ravin and Harry L. Malech took a different approach by directly injecting the retrovirus vector containing the corrective gene into the bloodstream of XSCID dogs with the hope of correcting the defective hematopoietic stem cells within the patient. The therapy completely restored immune function in three of the four dogs the researchers treated. The fourth dog received the lowest dose of the retrovirus vector the virus that had been engineered to pass on the gene leading Felsburg and his colleagues to believe that there is a lower limit to the dose before the treatment becomes effective. Since the boys involved in the French gene-therapy study did not develop leukemia until more than three years after the treatment began, the researchers have been particularly interested in knowing the long-term consequences of the trial. At 16 and 18 months following treatment, the two dogs involved in the long-term study have maintained their immune systems and remain, effectively, cured of XSCID, with no adverse side effects.

‘The results of this study show that this in-vivo approach to gene therapy may be a viable alternative for not only gene therapy of XSCID but perhaps other hematologic and immunologic diseases, thereby eliminating any potential detrimental effects of the ex-vivo manipulation and culture of cells that is required by current clinical gene therapy protocols,’ Felsburg said.
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