Gene therapy technique slows brain disease

	Progeny of HSCs that were engineered to carry the correct version of a gene (through the integration of a lentiviral vector) distribute throughout the body. Click here for more information.

A strategy that combines gene therapy with blood stem cell therapy may be a useful tool for treating a fatal brain disease, French, German, and U.S. researchers have found. Their research appears in the Nov. 5 issue of Science. In a pilot study of two patients monitored for two years, an international team of researchers X-linked adrenoleukodystrophy (ALD) using a lentiviral vector to introduce a therapeutic gene into patient’s blood cells. Featured in the movie “Lorenzo’s Oil,” ALD is a severe hereditary condition caused by a deficiency of a protein called ALD that is involved in fatty acid degradation. Sufferers steadily lose their myelin sheath, the protective layer that coats nerve fibers in the brain. Without myelin the nerves lose function, leading to increasing physical and mental disability in patients. X-linked ALD, the most common form of the disease, affects boys starting at age 6-8 years of age and death usually occurs before the patients reach adolescence. Bone marrow transplants typically slow progression of the disease, but finding a matching bone marrow donor can be a challenging and lengthy process, and the procedure carries considerable risks.

In the study, blood stem cells were removed from the patients and genetically corrected in the lab, using a lentiviral vector to introduce a working copy of the ALD gene into the cells. The modified cells were then infused back into the patients’ after they had received a treatment that destroyed their bone marrow. Two years later, healthy ALD proteins were still detectable in both patients’ blood cells. Encouragingly, both patients showed neurological improvement and a delay in disease progression comparable to that seen with bone marrow transplants. Although studies with larger cohorts of patients are needed, these results suggest that gene therapy with lentiviral vectors, which are derived from disabled versions of human immunodeficiency virus (HIV), could potentially become instrumental in treating a broad range of human disorders.

Article #10: "Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy," by N. Cartier; S. Hacein-Bay-Abina; M. Vidaud; B. l'Homme; A. Fischer; M. Cavazzana-Calvo; P. Aubourg; L. Dal-Cortivo; L. Caccavelli at INSERM in Paris, France; N. Cartier; S. Hacein-Bay-Abina; M. Vidaud; B. l'Homme; A. Fischer; M. Cavazzana-Calvo; P. Aubourg at University Paris, Descartes in Paris, France; N. Cartier; C. Bellesme; N. Lahlou; P. Bougneres; P. Aubourg at Hopital Saint-Vincent de Paul in Paris, France; S. Hacein-Bey-Abina; L. Dal-Cortivo; L. Caccavelli; N. Mahlaoui; S. Blanche; A. Fischer; F. Lefrere; M. Cavazzana-Calvo at Hopital Necker-Enfants Malades in Paris, France; S. Hacein-Bey-Abina; L. Dal-Cortivo; L. Caccavelli; M. Cavazzana-Calvo at Groupe Hospitalier Universitaire Ouest in Paris, France; C.C. Bartholomae; M. Schmidt; I. Kutschera; U. Abel; C. Von Kalle at National Center for Tumor Diseases in Heidelberg, Germany; C.C. Bartholomae; M. Schmidt; I. Kutschera; U. Abel; C. Von Kalle at German Cancer Research Center in Heidelberg, Germany; G. Veres in Gainesville, FL; V. Kiermer at Nature Publishing Group in New York, NY; D. Mittlestaedt in San Diego, CA; M. Audit at Genosafe in Evry, France; E. Payen; P. Leboulch at Institute of Emerging Diseases and Innovative Therapies in Fontenay-aux-Roses, France; E. Payen; P. Leboulch at INSERM in Fontenay-aux-Roses, France; E. Payen; P. Leboulch at Universite Paris XI in Fontenay-aux-Roses, France; P. Leboulch at Brigham and Women's Hospital in Boston, MA; P. Leboulch at Harvard Medical School in Boston, MA.