第632回 生医研セミナー(多階層生体防御システム研究拠点)
免疫機構研究セミナー


Naldini先生は現在汎用されているレンチウイルスベクターの開発者として世界的に有名です。 現在は本ベクターを用いた遺伝子治療の臨床応用を積極的に行っておられ、多くの顕著な業績をあげていらっしゃいます。 本セミナーでは、異染性白質ジストロフィ症に対する造血幹細胞遺伝子治療の最新のデータをご発表頂きます。
皆さんの積極的なご参加をお待ちしています。

演題 Near-Complete Genetic Engineering of Hematopoiesis with Substantial Therapeutic Benefit in Metachromatic Leukodystrophy after Lentiviral Hematopoietic Stem Cell Gene Therapy

演者Luigi Naldini, M.D. , PhD.
Professor, San Raffaele Telethon Institute for Gene Therapy and
Vita Salute San Raffaele University, Milan, Italy

日時平成24年10月1日(月)18時より19時まで

場所馬出医学系キャンパス内 総合研究棟 セミナー室 105
以下の地図の1番の建物になります。
http://www.kyushu-u.ac.jp/access/map/hospital/hospital.html

要旨 Metachromatic Leukodystrophy (MLD) is an autosomal recessive lysosomal storage disorder, characterized by inherited deficiency of the enzyme Arylsulfatase A (ARSA) and leading to severe progressive demyelination and neurodegeneration. Currently, no treatment can halt the progression or substantially delay the fatal outcome of this devastating disease. Whereas Hematopoietic Stem Cell (HSC) transplantation fails to provide consistent benefits in MLD, our preclinical studies had demonstrated that HSC gene therapy could prevent and correct the disease manifestations in the mouse model, based on the possibility to achieve extensive and supra-normal enzyme expression throughout the HSC progeny, which mediate widespread cross-correction of resident cells in the central and peripheral nervous system. Based on these studies and the development of a HSC transduction protocol attaining substantial levels of gene transfer, we have started a clinical trial of HSC gene therapy in early onset MLD. We report stable sustained ARSA gene replacement to nearly exhaustive levels in the reconstituted hematopoiesis of the first three treated late infantile MLD patients, resulting in supra-normal ARSA expression throughout the hematopoietic lineages. By ultra-deep monitoring of lentiviral vector integration sites we showed that the high gene marking levels were the results of highly polyclonal engraftment by the transduced cells, without evidence of aberrant clonal behavior ascribed to specific vector insertion. Importantly, the unprecedented extent of gene replacement achieved in post-transplant hematopoiesis was associated with substantial therapeutic benefit, as the disease had not progressed in any of the treated patients at the latest follow-up.

連絡先生体防御医学研究所 ゲノム病態学分野
谷 憲三朗
電話:092-642-6434


Copyright 2003 Medical Institute of Bioregulation Kyushu University. All Rights Reserved.