분자유전학실험실 (단국대학교 분자생물학과)



 이성욱 ( 2013-07-16 00:07:10 , Hit : 6141
 Gene therapy using HIV helps children with fatal diseases, study says


Gene therapy researchers say they used a safe version of HIV to prevent metachromatic leukodystrophy and halt Wiskott-Aldrich syndrome in children.

Italian researchers used gene therapy to treat children with two rare genetic diseases, according to a report in the journal Science.
Italian researchers used gene therapy to treat children with two rare genetic diseases, according to a report in the journal Science. (Peter and Maria Hoey/For the Times / July 11, 2013)

Ads by Google
By Melissa Pandika

July 11, 2013, 4:16 p.m.
Italian researchers have used a defanged version of HIV to replace faulty genes — and eliminate devastating symptoms — in children suffering two rare and fatal genetic diseases.

Improved gene therapy techniques prevented the onset of metachromatic leukodystrophy in three young children and halted the progression of Wiskott-Aldrich syndrome in three others.

The advance represents a major stride for a field that has struggled to translate experimental successes in lab animals into safe and effective treatments for people, experts said. Researchers may be able to use the team's method as a template, modifying it to treat a variety of diseases.

This is "ammunition for the gene therapy world," said Dr. Theodore Friedmann, a pediatric gene therapist at UC San Diego, who was not part of the study. "The field is slowly but surely making impressive advances against … quite untreatable diseases."

The scientists published results from the two clinical trials Thursday in the journal Science.

Metachromatic leukodystrophy affects just 1 in 40,000 to 1 in 160,000 people worldwide; Wiskott-Aldrich syndrome, only 1 to 10 per million males. But both illnesses are devastating. Children with late infantile metachromatic leukodystrophy, the most common form of that disease, begin having trouble walking about a year old and soon after experience muscle deterioration, developmental delays, paralysis and dementia. Most die within a few years of onset.

Kids with Wiskott-Aldrich syndrome suffer from eczema, bruising, nosebleeds and recurrent infections. Most develop at least one autoimmune disorder. A third get cancers, such as lymphoma and leukemia. Life expectancy ranges from 15 to 20 years.

The disorders are challenging — when not impossible — to treat. No therapy exists for metachromatic leukodystrophy. A bone marrow transplant can stop disease progression for the few Wiskott-Aldrich patients with an immunologically matched sibling, but they may experience severe side effects or death if the donor is not as close a match.

Both diseases are caused by inherited genetic mutations that disrupt the body's ability to produce crucial enzymes. In each trial, researchers took the normal form of the faulty gene and attached it to a virus derived from HIV that had been modified so that it could no longer cause AIDS.

The researchers removed bone marrow stem cells from the patients and then used the lentivirus to infect those cells with the normal genes.

The rest of the process resembled a traditional bone marrow transplant, with patients receiving chemotherapy to destroy their diseased bone marrow and then receiving infusions of the modified cells, which proliferated to form new marrow. Using the patients' own cells sidesteps problems of donor incompatibility.

The team treated the three metachromatic leukodystrophy patients before symptoms of the disorder had appeared. The kids stayed almost entirely symptom-free during the trial, up to two years after treatment. Gene therapy arrested the progression of disease in the Wiskott-Aldrich syndrome patients over up to two and a half years of follow-up.

Looking at the patients' bone marrow stem cells, the researchers found that 45% to 80% of the transplanted cells in the metachromatic leukodystrophy trial and 25% to 50% in the Wiskott-Aldrich trial produced the desired proteins, and continued to do so throughout roughly two years of follow-up.

That marked a major leap from a 2009 trial that used a similar approach to treat adrenoleukodystrophy, another degenerative disease. In that study, 15% of cells made the normal enzyme over the same time period.

Dr. Luigi Naldini, a scientist at the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy, who helped lead the trials, said his team fine-tuned the viral delivery method that had been pioneered in the 2009 study. Using the HIV-derived lentivirus was safer than relying on the mouse retroviruses tested in earlier gene therapy trials, because lentiviruses are less likely to activate cancer-causing genes near the target gene on a chromosome.

Naldini and his colleagues optimized the lentiviral techniques further, lessening cancer risk by tracking each modified stem cell — and its daughter cells — over time, and figuring out ways to grow purer, more concentrated lentivirus and to introduce the desired genes into cells more efficiently.

The group also fine-tuned their ability to wipe out enough resident bone marrow stem cells to make room for the modified cells, but not enough to have toxic effects.

Dr. Jennifer Puck, a pediatrician at UC San Francisco who was not involved in the research, praised the Italian team for getting such good results, even while incorporating safety modifications that tend to make such therapies less effective.

She cautioned, though, that the findings were still preliminary and that knowing whether the patients would remain free of immune deficiencies, cancer or neurological defects would take more than just a few years of follow-up.

Dr. Donald Kohn, a pediatric gene therapist at UCLA, who also wasn't involved in the study, said researchers may be able to use the team's method of delivering an HIV-packaged gene through patients' bone marrow stem cells as a template for treating a variety of diseases.

Besides about 50 other blood cell genetic disorders, such as sickle cell anemia, the therapy may also be adapted to AIDS, leukemia and other diseases involving the blood and immune cells that arise from bone marrow stem cells, he said.

melissa.pandika@latimes.com

Copyright © 2013, Los Angeles Times







1267    암억제유전자를 침묵시키는 안티센스 RNA  이성욱 2008/01/16 9791
1266   Bric에 올라온 ' 포항 Bio-festiva ' VOD 자료  송민선 2006/04/03 9471
1265   Dangerous Bacterium Hosts Genetic Remnant of Life's Distant Past  이성욱 2010/08/20 8979
1264   후손에게 전달되는 공포의 기억  이성욱 2013/12/06 8165
1263   운동이 뇌의 모세 혈관 부피를 증가시켜  정흥수 2003/11/12 8101
1262   인간과 헤르페스바이러스는 공생관계?  이성욱 2007/05/23 7341
1261   방사선을 먹는 진균 발견  이성욱 2007/05/25 7012
1260   노화의 원인을 제공하는 SIRT1의 딜레머: 유전자발현 통제 vs DNA 손상 회복  이성욱 2008/12/01 6824
1259   이빨의 개수와 기억력  정흥수 2004/11/05 6663
1258   피부줄기세포의 줄기성(stemness)을 억제하여 분화를 촉진하는 miR-203  이성욱 2008/03/10 6580
1257   Bcl2의 DNA 수복 저해기작 규명  이성욱 2008/03/07 6527
1256   피부암을 효과적으로 제거하는 5`-triphosphate-siRNA  이성욱 2008/12/03 6499
1255   siRNA를 암세포에 전달하는 효과적인 방법 개발: PTD-DRBD 융합단백질  이성욱 2009/05/20 6487
1254   패혈증의 사망원인이 되는 Histones  이성욱 2009/11/30 6429
1253   tRNA 합성효소의 이중기능(dual function)에 대한 미스터리 해명  이성욱 2009/12/18 6417
1252   흰머리가 생기는 원인을 세포 수준에서 규명  정흥수 2005/01/05 6386
1251   폐암 연구를 위한 키메라 생쥐 모델  이성욱 2010/02/03 6197
1250   에볼라바이러스의 전파를 저해하는 단백질: ISG15  이성욱 2008/03/07 6186
1249   인체 장내 미생물의 전체 분포 밝혀지다  이성욱 2010/03/10 6154
  Gene therapy using HIV helps children with fatal diseases, study says  이성욱 2013/07/16 6141

1 [2][3][4][5][6][7][8][9][10]..[64] [다음 10개]
 

Copyright 1999-2024 Zeroboard / skin by ROBIN