Stem Cells Treat Metatchromatic Leukodystrophy


Metachromatic  leukodystrophy is a genetic brain disease.  The exciting thing in the report below is that just using GMO stem cells (viral carrier for the corrected gene) to correct the bone marrow DNA was enough to arrest the disease, at least as far as was reported--the treatment is too new to report long term results.
The (potentially) cured patients would be GMO people, but be all the healthier for that.

Science DOI: 10.1126/science.1233158
  • RESEARCH ARTICLE

Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy

  1. Luigi Naldini1,4,§
+Author Affiliations
  1. 1San Raffaele Telethon Institute for Gene Therapy (TIGET), San Raffaele Scientific Institute, 20132 Milan, Italy.
  2. 2TIGET Pediatric Clinical Research Unit, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy.
  3. 3Pediatric Immunohematology and Bone Marrow Transplant Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
  4. 4Vita-Salute San Raffaele University, 20132 Milan, Italy.
  5. 5Neurology Unit, Department of Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy.
  6. 6Neuroradiology Unit, Head and Neck Department, San Raffaele Scientific Institute, 20132 Milan, Italy.
  7. 7Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06122 Perugia, Italy.
  8. 8MolMed S.p.A., 20132 Milan, Italy.
  9. 9Distributed Computing Group, Center for Advanced Studies, Research and Development in Sardinia (CRS4), 09010 Pula, Italy.
  10. 10Pediatric Hematology Oncology Division, Rafic Hariri University Hospital, Beirut, Lebanon.
  11. 11Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  12. 12Molecular and Cellular Technologies, GlaxoSmithKline, Stevenage 5G1 2NY, UK.
  13. 13Pediatric Blood and Marrow Transplantation Program, University Medical Center 3584 CX Utrecht, Netherlands.
  14. 14Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, 69120 Heidelberg, Germany.
  15. 15Hematology and Bone Marrow Transplant Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
  16. 16Center for Translational Genomics and BioInformatics, San Raffaele Scientific Institute, 20132 Milan, Italy.
  17. 17Regenerative Medicine Discovery Performance Unit, GlaxoSmithKline Research and Development, King of Prussia, PA 19406, USA.
  18. 18Bone Marrow Transplant Unit, MBBM Foundation, Pediatric Department, Milano-Bicocca University at San Gerardo Hospital, 20052 Monza, Italy.
  19. 19University of Rome Tor Vergata, 00133 Rome, Italy.
  1. §To whom correspondence should be addressed. E-mail: biffi.alessandra@hsr.it (A.B.); naldini.luigi@hsr.it (L.N.)
  1. * These authors contributed equally to this work.
Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disease caused by arylsulfatase A (ARSA) deficiency. Patients with MLD exhibit progressive motor and cognitive impairment and die within few years of symptom onset. We used a lentiviral vector to transfer a functional ARSA gene into hematopoietic stem cells (HSCs) from three presymptomatic patients who showed genetic, biochemical, and neurophysiological evidence of late infantile MLD. After reinfusion of the gene-corrected HSCs, the patients showed extensive and stable ARSA gene replacement, which led to high enzyme expression throughout hematopoietic lineages and in cerebrospinal fluid. Analyses of vector integrations revealed no evidence of aberrant clonal behavior. Notably, the disease did not manifest or progress in the three patients 7 to 21 months beyond the predicted age of symptom onset. These findings indicate that extensive genetic engineering of human hematopoiesis can be achieved with lentiviral vectors and that this approach may offer therapeutic benefit for MLD patients.

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