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Category Archives: Gene Therapy

MPs to vote 'soon' on new gene therapy – pioneered by Newcastle University team

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MPs will vote soon on a new gene therapy to stop incurable diseases passing to babies ending fears the Government is ducking the controversy.

The health minister threw her weight behind a DNA-altering procedure pioneered by a team at Newcastle University, saying: This is something I want to take forward.

Jane Ellison told a parliamentary inquiry: I am now actively seeking cross-Government approval for parliamentary time in this session to bring regulations before the House.

Im extremely conscious that there are real families waiting on progress on this work. We need to keep up the momentum.

The comments are a huge boost to the Newcastle team, which has called for legislation as soon as possible, because of the number of patients waiting for treatment.

Also appearing before the Commons science select committee, the teams Professor Doug Turnbull said the worst-affected babies died within 24 or 48 hours.

He said most diseases develop in childhood, or adolescence, adding: We can do a lot to help with epilepsy and diabetes, but there is no cure.

And, on the gene therapy, This sort of approach to try to present a transmission of these sorts of diseases - would be really important.

The treatment involves replacing faulty mitochondria responsible for inherited diseases, including muscle wasting, heart problems, vision loss, organ failure and epilepsy.

Embryos are given healthy DNA from donor eggs, meaning a baby has the DNA of three people from two parents, plus less than one per cent from the donor.

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MPs to vote 'soon' on new gene therapy - pioneered by Newcastle University team

With Collaboration, Scientists Test Gene Therapy for 'Bubble Boy Disease'

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A new variation of gene therapy raises hopes for a safe and effective long-term treatment for X-linked severe combined immunodeficiency syndrome (SCID-X1), a life-threatening heritable disorder.

The research was produced by a collaborative research team from Dana-Farber/Boston Children's Cancer and Blood Disorders Center, along with other institutions participating in an international clinical trial that involved boys from the United States and France.

SCID-X1, dubbed bubble boy disease after a patient who lived for 12 years in a sterile bubble, is a rare genetic disorder that hinders the ability of individuals to combat infections. Because the disease is carried in an X-chromosome recessive pattern, the disorder occurs almost only in males. The resulting mutations inactivate a gene called IL-2 receptor gamma (IL2RG), severely weakening immune system functions. Left untreated, individuals who inherit the disorder usually die within a year.

Previous gene therapy trials conducted in Europe over a decade ago promised dramatic progress, until a quarter of patients developed leukemia about two to five years following treatment. Scientists found that the previously used vectorthe device for transporting the correct gene in therapyinadvertently activated oncogenes, which can cause cancer.

In this new study, the vector in use is a self-inactivating gammaretrovirus, which has a specific sequence deleted that basic research had implicated in the process of inappropriate activation of oncogenes, David A. Williams, chief of the hematology/oncology department at Boston Children's Hospital, wrote in an email.

Of the nine patients who underwent the treatment, eight had survived between 12 and 38 months after treatment. One boy died from a severe infection he was fighting at the time he enrolled in the study.

A single round of therapy restored normal disease-fighting T cell count300 cells or more per microliter of bloodin six of the eight patients. One patient underwent a second round of treatment and remains healthy despite a low cell count. The eighth patient received a hematopoietic stem cell transplant after the therapy led to less than optimal uptake of the virus and failed to stimulate T-cell production, according to Williams.

We feel the surrogate assays for safety look excellent and are very encouraged, Williams said. However, because leukemia can take years to develop (and although some of our patients are now approaching 4 years of [follow-up]) we must be cautious and continue to follow these children closely.

Williams noted that the research was the result of positive collaboration between institutions.

Work by Sung-Yun Pai and Gigi Notarangelo, funding from [Boston Childrens Hospital] (and other childrens hospitals) and [the National Institute of Health] were essential for success, he said. This is the first international collaborative trial in stem cell gene therapy, which was critical for success due [to the] rarity of [this] disease.

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With Collaboration, Scientists Test Gene Therapy for 'Bubble Boy Disease'

New Gene Therapy for "Bubble Boy" Disease Appears to be Safe, Effective

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PHILADELPHIA A new form ofgene therapyfor boys with X-linked severe combined immunodeficiency syndrome (SCID-X1), a life-threatening condition also known as bubble boy disease, appears to be both effective and safe, according to an international clinical trial with sites inBoston, Cincinnati, Los Angeles, London, and Paris.

Early data published in theNew England Journal of Medicinesuggests that the therapy may avoid the late-developing leukemiaseen in a quarter of SCID-X1 patients in previous gene-therapy trials in Europe that took place more than a decade ago. Left untreated, boys with SCID-X1 usually die of infection before their first birthday.

The lab of coauthorFrederic Bushman, PhD, professor of Microbiology, from thePerelman School of Medicine at the University of Pennsylvania, carried out the deep DNA sequencing on patient specimens to track and verify distributions of integration sites of the vector.The vector used in the new trial was engineered to remove molecular signals implicated in cancers in the first trial.

Eight of nine boys recruited to date to the present trial are alive between 12 and 38 months after treatment, with no SCID-X1-associated infections. The gene therapy alone generated functioning immune systems in seven of eight boys. Genetic studies showed that the new viral vector did not lead to vector insertions near known cancer-causing genes, raising cautious hopes about the vector's long-term safety.

We showed that fewer cells accumulated with integration sites near cancer genes in the second trial, suggesting that the adverse properties had indeed been engineered out, explains Bushman So far there are no clinical adverse events in the present trial -- the integration site data has suggested improved safety.

The modified vector created for the current trial is a self-inactivating gammaretrovirus, designed to deliver its payload effectively while minimizing the chance of inadvertently turning on oncogenes that could lead to leukemia.

The core question of the trial was whether the new self-inactivating viral vector could safely and successfully shuttle a gene called theIL-2 receptor gamma(IL2RG) subunit into the patients' hematopoietic stem cells. In boys born with SCID-X1, mutations render theIL2RGgene inactive, robbing the children of the ability to produce a functional immune system.

For more information, see theDana-Farber/Boston Children's Cancer and Blood Disorders Centersnews release.

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Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of theRaymond and Ruth Perelman School of Medicine at the University of Pennsylvania(founded in 1765 as the nation's first medical school) and theUniversity of Pennsylvania Health System, which together form a $4.3 billion enterprise.

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New Gene Therapy for "Bubble Boy" Disease Appears to be Safe, Effective

Gene therapy offers a safe and effective way to treat bubble boy disease Health Updates – Video

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Gene Therapy Shows Potential for 'Bubble Boy' Disease

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Amy Norton HealthDay Reporter Posted: Thursday, October 9, 2014, 5:00 AM

(HealthDay News) -- A new form of gene therapy may offer a safe and effective way to treat "bubble boy" disease -- a severe immune deficiency that is fatal unless treated in infancy.

Researchers have long known that gene therapy can cure the disease, known medically as severe combined immunodeficiency, or SCID. Over a decade ago, trials in Europe showed that gene therapy worked -- but five of the 20 children treated developed leukemia (a type of cancer) within two to five years, according to background information in the study.

In the new trial, reported in the Oct. 9 New England Journal of Medicine, researchers refined the gene therapy approach to hopefully negate the leukemia risk.

Eight of nine children who received the therapy are still alive one to three years later, the investigators report. And so far, none has developed leukemia.

It's too early to say the therapy carries no leukemia risk, cautioned researcher Dr. David Williams, a pediatric hematologist/oncologist at Dana-Farber Cancer Institute and Boston Children's Hospital.

"We'll continue to follow these children for 15 years," Williams said.

But based on the early results, he noted, the tweaked gene therapy appears as effective at generating a functional immune system as the earlier form of treatment.

SCID refers to a group of rare genetic disorders that all but eliminate the immune system, according to the Immune Deficiency Foundation (IDF). That leaves children at high risk of severe infections.

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Gene Therapy Shows Potential for 'Bubble Boy' Disease

Gene therapy shows promise for severe combined immunodeficiency

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PUBLIC RELEASE DATE:

8-Oct-2014

Contact: Hillary Hoffman hillary.hoffman@nih.gov 301-402-1663 NIH/National Institute of Allergy and Infectious Diseases @NIAIDNews

Researchers have found that gene therapy using a modified delivery system, or vector, can restore the immune systems of children with X-linked severe combined immunodeficiency (SCID-X1), a rare, life-threatening inherited condition that primarily affects boys. Previous efforts to treat SCID-X1 with gene therapy were initially successful, but approximately one-quarter of the children developed leukemia two to five years after treatment. Results from a study partially funded by the National Institute of Allergy and Infectious Diseases (NIAID), a component of the National Institutes of Health (NIH), suggest that the new vector is equally effective at restoring immunity and may be safer than previous approaches.

In SCID-X1, mutations in a specific gene prevent the development of infection-fighting T cells. The standard therapy for SCID is transplantation of blood-forming stem cells, but some patients lack a suitable donor. In gene therapy, doctors remove stem cells from the patient's bone marrow, use a vector to insert a corrected gene and then return the corrected cells to the patient. Scientists suspect that the vectors used in earlier studies may have activated genes that control cell growth, contributing to leukemia.

In the current study, nine boys with SCID-X1 underwent gene therapy using a vector engineered by the study researchers. Seven boys developed functional T cells at levels comparable to those seen in previous studies and have remained healthy for one to three years after treatment. Analyses of the children's T cells suggest that the new vector causes fewer genomic changes that could be linked to leukemia. Researchers will continue to monitor the boys for leukemia development. Of the two other boys, one died of a pre-existing viral infection shortly after receiving the therapy, and one failed to develop corrected T cells and was given a stem cell transplant from an unrelated donor.

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ARTICLE:

S Hacein-Bey-Abina, S-Y Pai et al. A modified y-retrovirus vector for X-linked severe combined immunodeficiency. New England Journal of Medicine DOI: 10.1056/NEJMoa1404588 (2014).

WHO:

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Gene therapy shows promise for severe combined immunodeficiency


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