local injection of gene therapy
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Category Archives: Gene Therapy
GENETHON and ESTEVE announce agreement to manufacture the gene therapy for the treatment of Sanfilippo syndrome
PUBLIC RELEASE DATE:
11-Mar-2014
Contact: Press Office presse@afm.genethon.fr AFM-Tlthon
France March 11, 2014 ESTEVE, a Spanish pharmaceutical company devoted to the research, development, manufacturing and commercialization of novel medicines and Genethon, a nonprofit organization dedicated to the research and development of gene therapies for orphan genetic diseases, announce that they have entered into an agreement to manufacture Esteves investigational gene therapy for the treatment of Sanfilippo A Syndrome, AAV9-hsulfamidase, under GMP.
"We are very happy to contribute to the development of the treatment for Sanfillippo A developed by Esteve. The quality of the project and of the teams both academic and industrial participating in the program is outstanding and it is our goal to support clinical development with our biomanufacturing expertise, in the most efficient way, and in the best interest of patients" explained Frdric Revah, Chief Executive Officer of Genethon.
"The signature of this agreement with Genethon is a new milestone for ESTEVE, as it enables us to advance the development of our gene therapeutic for Sanfilippo A towards clinical trials. We are very pleased to collaborate with Genethon, a reference center in manufacturing of gene therapies for rare diseases. Our mission at ESTEVE R&D is the development of innovative products to meet patient needs and that is why this is one of our highest priority projects today." said Albert Esteve, CEO of ESTEVE.
ESTEVE is developing the Sanfilippo project in a Public and Private Partnership (PPP) with the Universitat Autnoma de Barcelona (UAB) for the development of gene therapies for mucopolysaccharidoses. The program relies on state-of-the art science developed at the CBATEG (Center of Animal Biotechnology and Gene Therapy) of the UAB. The most advanced project in this program is the development of a novel gene therapy treatment for Sanfilippo A Syndrome.
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About MPS III A (Sanfilippo syndrome Type A)
Sanfilippo A Syndrome is a devastating disease that leads to progressive and significant deterioration in mental status of children who rarely live beyond their twenties. Diagnosis of many rare diseases are lengthy and time consuming and is only initiated once the symptoms have begun to appear like the Sanfilippo Syndrome, a lysosomal storage disease caused by the loss of the activity of the enzyme sulfamidase. It affects approximately 1 in 100,000 births and is still largely underdiagnosed.
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ESTEVE and UAB advance in their program to develop a cure for Sanfilippo A Syndrome
PUBLIC RELEASE DATE:
11-Mar-2014
Contact: M. Angels Valls avalls@esteve.es 34-934-466-286 Universitat Autonoma de Barcelona
ESTEVE has announced the signing of two agreements that will enable it to progress the development of its gene therapeutic for the treatment of Mucopolysaccharidosis type IIIA (MPSIIIA or Sanfilippo A Syndrome) and begin a phase I/II clinical trial in 2015. The agreements are with the North American biotechnology company REGENX Biosciences, LLC (REGENX) and with the French non for profit organization GNTHON.
The license agreement with REGENX grants ESTEVE the right to use the adeno-associated viral vector, NAV rAAV9, in the development and commercialization of its investigational gene therapy for the treatment of Sanfilippo A Syndrome. The vector NAV rAAV9 is an integral part of the investigational therapeutic and enables the gene for the enzyme Sulfamidase, missing or defective in patients with Sanfilippo A Syndrome, to be delivered to and enter cells such as neurons and hepatocytes. Once inside the cells the gene expresses the Sulfamidase enzyme stably, compensating for its absence hence addressing the cause of the disease. The agreement with GNTHON is for the development of the manufacturing process of the investigational gene therapeutic and its production for clinical trial use. The process to be developed will allow the production of the therapeutic for preclinical toxicology studies, the clinical trial and eventually for commercial use.
Public-private partnership ESTEVE-UAB
The Sanfilippo project was initiated by the research team of Dr. Ftima Bosch at the Center for Biotechnology and Gene Therapy (CBATEG) of UAB and since 2009 is being developed within the framework of a public-private partnership between ESTEVE and the University, aimed at developing gene therapies for the treatment of this syndrome and related diseases called mucopolysaccharidoses. This research project was initiated at the CBATEG due to the petition of the Asociacin MPS-Fabry Espaa.
In this partnership, ESTEVE leads all activities associated with the management and protection of intellectual property, regulatory activities, the coordination and supervision of GMP manufacturing, the preclinical toxicology studies as well as all clinical development. The CBATEG research team at the UAB brings to the partnership their scientific know-how and expertise in gene therapy including viral vector design and the development of preclinical disease models.
The investigational gene therapeutic consists of the viral NAV rAAV9, licensed from REGENX, which contains a version of the gene that codes for Sulfamidase that has been optimized to improve its expression levels. Experimentation using preclinical disease models performed by the CBATEG have validated the potential efficacy of this therapeutic approach. The treatment consists in the administration of gene therapy in the cerebrospinal fluid, the fluid that bathes the brain and spinal cord. The viral vector NAV rAAV9 has the advantage of its high affinity for the brain (main organ affected in this disease) than many of the other adeno-associated viral vectors, is harmless, not being known to cause any disease in humans. For its part, once the gene for the Sulfamidase enzyme reaches the cytoplasm of the neuron, it begins the production of the enzyme. Thus, it is produced enzyme which is secreted into spinal fluid, allowing its distribution throughout the brain and spinal cord and also reaching those neurons in which does not incorporate any viral vector. Furthermore, a small proportion of the gene therapeutic passes from the CSF into the peripheral circulatory system, thereby reaching organs such as the liver where it can enter hepatocytes and subsequently produce and secrete the Sulfamidase enzyme which then distributes throughout the body with the aid of the bloodstream.
In the preclinical disease model studied, after administering the gene therapeutic, the levels of Sulfamidase activity significantly increase both in the brain and the rest of the body, the accumulated glycosaminoglycans (substances that build up as a consequence of the disease) are eliminated from within cells, and signs of neuroinflammation disappear. Finally, and most importantly, the behavior is restored and the lifespan is prolonged close to normal.
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ESTEVE and UAB advance in their program to develop a cure for Sanfilippo A Syndrome
HIV progress: Manipulating genes to reject virus – Video
HIV progress: Manipulating genes to reject virus
Using gene editing, researchers are trying to create HIV immunity. CBS News medical correspondent Dr. Jon LaPook explains the latest gene therapy.
By: CBS This Morning
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BBC News HIV Gene therapy breakthrough patients on medication – Video
BBC News HIV Gene therapy breakthrough patients on medication
thanks for all sources.
By: LoveInn-Baylagan
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BBC News HIV Gene therapy breakthrough patients on medication - Video
Gene therapy shows promise for HIV control
Scientists have modified genes in the blood cells of HIV patients to help them resist the AIDS virus, and say the treatment seems safe and promising. The results give hope that this approach might one day free at least some people from needing medicines to keep HIV under control, a form of cure.
The idea came from an AIDS patient who appears cured after getting a cell transplant seven years ago in Berlin from a donor with natural immunity to HIV. Only about 1 percent of people have two copies of the gene that gives this protection.
Researchers are seeking a more practical way to get similar results by using gene therapy to modify patients' own blood cells.
A study of this in 12 patients was led by Dr. Carl June at the University of Pennsylvania. Results are in Thursday's the New England Journal of Medicine. These are the first published results from this method, which also has been tried in several smaller studies of patients in California.
HIV usually infects blood cells through a protein on their surface, a "docking station" called CCR5. A California company, Sangamo BioSciences Inc., makes a treatment that can knock out a gene that makes CCR5.
The 12 HIV patients had their blood filtered to remove some of their cells. The gene-snipping compound was added in the lab, and the cells were infused back into the patients.
Four weeks later, half of the patients were temporarily taken off AIDS medicines to see the gene therapy's effect. The virus returned in all but one of them, but the modified cells seemed to be protected from HIV infection and were more likely to survive than the cells that had not been treated.
"We knew that the virus was going to come back in most of the patients," but the hope is that the modified cells eventually will outnumber the rest and give the patient a way to control viral levels without medicines, said Dr. Pablo Tebas, one of the Penn researchers. That would be what doctors call a "functional cure," because the virus would still be present but held in check without treatment.
The lone patient whose HIV did not return turned out to have one copy of the protective gene, so "nature had done half of the job already," Tebas said.
The National Institute of Allergy and Infectious Diseases sponsored the work with Sangamo and Penn.
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Could gene therapy hold key in AIDS fight? – Video
Could gene therapy hold key in AIDS fight?
An experimental treatment for HIV at the University of Pennsylvania is using gene therapy to help prevent the virus from developing into AIDS. Doctors extrac...
By: CBS Evening News
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Medical breakthrough: HIV gene therapy – Video
Medical breakthrough: HIV gene therapy
U.S. scientists are using gene therapy for the first time to boost the immune system of people with HIV, which may help them in reducing the daily intake of ...
By: Romila De Munshi
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Gene Therapy Market – Global Industry Analysis, Size, Share, Growth, Trends And Forecast, 2013 – 201 – Video
Gene Therapy Market - Global Industry Analysis, Size, Share, Growth, Trends And Forecast, 2013 - 201
Browse Full Report with TOC: http://www.transparencymarketresearch.com/gene-therapy-market.html - Gene therapy involves use of DNA as a pharmaceutical agent ...
By: Alina Martin
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Dr. Max Gomez: HIV Gene Therapy – Video
Dr. Max Gomez: HIV Gene Therapy
Genetically engineered white blood cells could mark the beginning of a cure for AIDS. CBS 2 #39;s Dr. Max Gomez has more. Subscribe Here: http://www.youtube.com/...
By: CBS New York
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Gene Therapy for Controlling HIV Shows Early Promise
By Amy Norton HealthDay Reporter
WEDNESDAY, March 5, 2014 (HealthDay News) -- In an early step toward drug-free HIV therapy, researchers are reporting the first success in genetically "editing" T-cells in patients' immune systems to become resistant to the virus.
The findings, published in the March 6 issue of the New England Journal of Medicine, are based on only 12 patients. But experts were cautiously optimistic about what the study accomplished.
Specifically, researchers were able to take T-cells from the HIV patients' blood, then "knock out" a gene known as CCR5, which controls a protein that allows HIV to enter a cell.
The scientists then infused the genetically altered T-cells back into patients' blood, where they expanded in number. What's more, a few patients were taken off their HIV drugs temporarily and saw their virus levels decrease.
"This is impressive," said Rowena Johnston, director of research for amfAR, the Foundation for AIDS Research.
The altered T-cells "actually seem to be doing exactly what [the researchers] wanted them to," said Johnston, who was not involved in the study.
Still, she said, there are plenty of questions left and much research ahead. The investigators on the study agreed.
"This was a first-in-human study," said researcher Bruce Levine, an associate professor of cancer gene therapy at the University of Pennsylvania School of Medicine, in Philadelphia.
That means the trial was designed to see whether it's even safe to use this approach in people with HIV -- and not whether it's an effective therapy.
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Localized Therapeutics – a localized photo-inducible gene therapy for arthritis – Video
Localized Therapeutics - a localized photo-inducible gene therapy for arthritis
http://localizedtherapeutics.com.
By: Max Rempel
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Localized Therapeutics - a localized photo-inducible gene therapy for arthritis - Video
Europe Nears First Approval for Gene Therapy Treatment
China was the first country to approve a gene therapy product for commercial use, in 2004. The U.S. has yet to endorse any such treatments and the field has been plagued by carcinogenicity
Flickr/hermida
From Nature magazine
Europes drugs regulator has for the first time recommended a gene therapy medicine for approval.
Glybera, a treatment for patients who cannot produce enough of an enzyme crucial for breaking down fat, was backed by the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP). This recommendation has to be endorsed by the European Commission before it becomes available, but it would be unusual for the Commission to reject the recommendation.
Gene therapy involves transferring genes into patients to treat their diseases. In this case Glybera uses a virus injected into a patient to deliver a working copy of a gene for producing lipoprotein lipase (LPL). LPL deficiency affect no more than one or two people in a million.
Back in 2004 China became the first country to approve a gene therapy product for commercial use, with a treatment for cancer. But Europe and the United States have yet to endorse any gene therapy treatments and the field has been plagued by issues such as carcinogenicity.
Jrn Aldag, chief executive of uniQure, the Amsterdam-based company that owns Glybera, says todays announcement from the EMA is an overdue signal to the gene therapy community that things are changing. It unlocks the potential, he told Nature. You will see more investment coming.
Fantastic news Tim Cot, former head of the US Food and Drug Administrations Office of Orphan Products Development and now an independent consultant, says the approval is "astounding, fantastic news. It puts Europe at the forefront.
Glybera had previously received negative opinions from both the CHMP and the EMA Committee for Advanced Therapies (CAT), which advises on cutting edge treatments. However, after re-evaluating the treatment in just those patients who experience severe or multiple attacks of pancreatitis as a result of LPL deficiency, the CAT gave a positive opinion in June, and this has now been endorsed by the CHMP.
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Sight Seen: Gene Therapy Restores Vision in Both Eyes
Two doses of gene therapy restore vision to three women who were born nearly blind
Garretttaggs55, Wikimedia Commons
Gene therapy has markedly improved vision in both eyes in three women who were born virtually blind. The patients can now avoid obstacles even in dim light, read large print and recognize people's faces. The operation, researchers predict, should work even better in children and adolescents blinded by the same condition.
The advance, reported in the February 8 issue of Science Translational Medicine, extends earlier work by the same group. Between 2008 and 2011, Jean Bennett of the University of Pennsylvania's Mahoney Institute of Neurological Sciences and her colleagues used gene therapy to treat blindness in 12 adults and children with Leber's congenital amaurosis (LCA), a rare inherited eye disease that destroys vision by killing photoreceptorslight-sensitive cells in the retina at the back of the eye. Typically, afflicted children start life with poor vision, which worsens as more and more photoreceptors die.
The treatment grew out of the understanding that people with the disorder become blind because of genetic mutations in retinal cells. One mutated gene that causes the disorder is named RPE65. An enzyme encoded by RPE65 helps break down a derivative of vitamin A called retinol into a substance that photoreceptors need to detect light and send signals to the brain. Mutant forms of RPE65 prevent the production of this enzyme in a "nursery" layer of cells called the retinal pigment epithelium, which is attached to the retina and nourishes photoreceptors by breaking down retinol, among other cellular services.
In the initial study, retina specialist and Bennett's co-author Albert Maguire of Penn Medicine injected a harmless virus carrying normal copies of RPE65 into an area of the retinal pigment epithelium, which subsequently began producing the enzyme. In each of the 12 patients, Maguire treated one eyethe one with worse vision. Six patients improved so much they no longer met the criteria for legal blindness.
In the new study, Maguire injected the functional genes into the previously untreated eye in three of the women from the first group. Bennett followed the patients for six months after their surgeries. The women's vision in their previously untreated eye improved as soon as two weeks after the operation: They could navigate an obstacle course, even in dim light, avoiding objects that had tripped them up before, as well as recognize people's faces and read large signs. Bennett showed that not only were the women's eyes much more sensitive to light, their brains were much more responsive to optical input as well. Functional magnetic imaging showed regions of their visual cortices that had remained offline before gene therapy began to light up.
Surprisingly, Bennett reports, the second round of gene therapy further strengthened the brain's response to the initially treated eye as well as the newly treated one. "That wasn't something we had been expecting, but it makes sense because the two eyes act in concert, and some aspects of vision rely on binocularity." In the new paper, the authors suggest that neuroplasticity plays a role: It is possible that regions of the visual cortex responding to the newly flowing channel of information from the second eye bolster activity in areas of the visual cortex responding to the initially treated eye.
An institutional review board required that Bennett work with adults in the follow-up study, but she thinks the therapy will work even better in younger patients who have not lost as many photoreceptors. She says the results "really bode well" for restoring meaningful vision to people with LCA and other forms of inherited blindness.
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Gene therapy used to block HIV without drugs
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In a small trial, researchers have successfully used gene therapy to boost the immune system of 12 patients with HIV to resist infection. They removed the patients' white blood cells to edit a gene in them, then infused them back into the patients. Some of the patients who showed reduced viral loads were off HIV drugs completely.
In fact, one of the patients showed no detectable trace of HIV at all after therapy. The researchers, who report their phase I study in the New England Journal of Medicine believe theirs is the first published account of using gene editing in humans.
The team included researchers from the University of Pennsylvania (Penn), PA, Albert Einstein College of Medicine, Bronx, NY, and Sangamo BioSciences, Richmond, CA, the company that developed the gene editing technology.
Carl H. June, senior author of the study and professor at Penn's Perelman School of Medicine, says:
"This study shows that we can safely and effectively engineer an HIV patient's own T cells to mimic a naturally occurring resistance to the virus, infuse those engineered cells, have them persist in the body, and potentially keep viral loads at bay without the use of drugs."
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Gene-Editing Technique Shown to Work as HIV Treatment
The approach involves using enzymes to destroy a gene in the immune cells of people with HIV, thereby increasing resistance to the virus
Scanning electron micrograph of a human T cell from the immune system of a healthy donor. Credit:NIAID/NIH - Wikimedia Commons
A clinical trial has shown that a gene-editing technique can be safe and effective in humans. For the first time, researchers used enzymes called zinc-finger nucleases (ZFNs) to target and destroy a gene in the immune cells of 12 people with HIV, increasing their resistance to the virus. The findings were published March 5 in The New England Journal of Medicine.
This is the first major advance in HIV gene therapy since it was demonstrated that the Berlin patient Timothy Brown was free of HIV, says John Rossi, a molecular biologist at the Beckman Research Institute of the City of Hope National Medical Center in Duarte, California. In 2008, researchers reported thatBrown gained the ability to control his HIV infectionafter they treated him with donor bone-marrow stem cells that carried a mutation in a gene calledCCR5. Most HIV strains use a protein encoded byCCR5as a gateway into the T cells of a hosts immune system. People who carry a mutated version of the gene, including Brown's donor, are resistant to HIV.
But similar treatment isnot feasible for most people with HIV: it is invasive, and the body is likely to attack the donor cells. So a team led by Carl June and Pablo Tebas, immunologists at the University of Pennsylvania in Philadelphia, sought to create the beneficialCCR5 mutation in a persons own cells, using targeted gene editing.
Personalized medicine The researchers drew blood from 12 people with HIV who had been taking antiretroviral drugs to keep the virus in check. After culturing blood cells from each participant, the team used a commercially available ZFN to target theCCR5gene in those cells. The treatment succeeded in disrupting the gene in about 25% of each participants cultured cells; the researchers then transfused all of the cultured cells into the participants. After treatment, all had elevated levels of T cells in their blood, suggesting that the virus was less capable of destroying them.
Six of the 12 participants then stopped their antiretroviral drug therapy, while the team monitored their levels of virus and T cells. Their HIV levels rebounded more slowly than normal, and their T-cell levels remained high for weeks. In short, the presence of HIV seemed to drive the modified immune cells, which lacked a functionalCCR5gene, to proliferate in the body. Researchers suspect that the virus was unable to infect and destroy the altered cells.
They used HIV to help in its own demise, says Paula Cannon, who studies gene therapy at the University of Southern California in Los Angeles. They throw the cells back at it and say, Ha, now what?
Long-term action In this first small trial, the gene-editing approach seemed to be safe: Tebas says that the worst side effect was that the chemical used in the process made the patients bodies smell bad for several days.
The trial isnt the end game, but its an important advance in the direction of this kind of research, says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. Its more practical and applicable than doing a stem-cell transplant, he says, although it remains to be seen whether it is as effective.
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Can Gene Therapy Cure HIV?
Engineering a patients own immune cells to resist HIV could eliminate the need for lifelong antiretroviral therapies.
The immune cells of HIV patients can be genetically engineered to resist infection, say researchers. In a small study in humans, scientists report that by creating a beneficial mutation in T cells, they may be able to nearly cure patients of HIV.
In a study published in the New England Journal of Medicine on Wednesday, researchers report that they can use genome editing to re-create the rare mutations responsible for protecting about 1 percent of the population from the virus in infected patients. They report that some of the patients receiving the genome-modifying treatment showed decreased viral loads during a temporary halt of their antiretroviral drugs. In one patient, the virus could no longer be detected in his blood.
Zinc-finger nucleases are one of a few genome-editing tools that researchers use to create specific changes to the genomes of living organisms and cells (see Genome Surgery). Scientists have previously used genome-editing techniques to modify DNA in human cells and nonhuman animals, including monkeys (see Monkeys Modified with Genome Editing). Now, the NEJM study suggests the method can also be safely used in humans.
From each participating patient, the team harvested bone marrow stem cells, which give rise to T cells in the body. They then used a zinc finger nuclease to break copies of the CCR5 gene that encodes for proteins on the surface of immune cells that are a critical entry point of HIV. The stem cells were then infused back into each patients bloodstream. The modification process isnt perfect, so only some of the cells end up carrying the modification. About 25 percent of the cells have at least one of the CCR5 genes interrupted, says Edward Lanphier, CEO of Sangamo Biosciences, the Richmond, California, biotech company that manufactures zinc finger nucleases.
Because the cells are a patients own, there is no risk of tissue rejection. The modified stem cells then give rise to modified T cells that are more resistant to infection by HIV, say the researchers.
One week after the infusion, researchers were able to find modified T cells in the patients blood. Four weeks after the infusion, six of the 12 patients in the study temporarily stopped taking their antiretroviral drugs so the researchers could assess the effect of the genome-editing treatment on the amount of the virus in the patients bodies. In four of these patients, the amount of HIV in the blood dropped. In one patient, the virus could no longer be detected at all. The team later discovered that this best responder had naturally already had one mutated copy of the CCR5 gene.
Patients who carry one broken copy of the CCR5 progress to AIDS more slowly than those who dont, says Bruce Levine, a cell and gene therapy researcher at the University of Pennsylvania School of Medicine and coauthor on the study. Because all of the cells in that best-responder patient already carried one disrupted copy of CCR5, the modification by the zinc finger nuclease led to T cells with no functional copies of the gene. That means the cells are fully resistant to HIV infection. The team is now working to increase the number of immune cells that end up carrying two broken copies of CCR5.
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Gene therapy locks out HIV, paving the way to control virus without antiretroviral drug
PUBLIC RELEASE DATE:
5-Mar-2014
Contact: Steve Graff stephen.graff@uphs.upenn.edu 215-349-5653 University of Pennsylvania School of Medicine
PHILADELPHIAUniversity of Pennsylvania researchers have successfully genetically engineered the immune cells of 12 HIV positive patients to resist infection, and decreased the viral loads of some patients taken off antiretroviral drug therapy (ADT) entirelyincluding one patient whose levels became undetectable. The study, appearing today in the New England Journal of Medicine, is the first published report of any gene editing approach in humans.
The phase I study was co-authored by researchers at Penn Medicine, the Albert Einstein College of Medicine and scientists from Sangamo BioSciences, which developed the zinc finger nuclease (ZFN) technology, the T cell therapy approach used in the clinical trial.
"This study shows that we can safely and effectively engineer an HIV patient's own T cells to mimic a naturally occurring resistance to the virus, infuse those engineered cells, have them persist in the body, and potentially keep viral loads at bay without the use of drugs," said senior author Carl H. June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine at Penn's Perelman School of Medicine. "This reinforces our belief that modified T cells are the key that could eliminate the need for lifelong ADT and potentially lead to functionally curative approaches for HIV/AIDS."
June and his colleagues, including Bruce L. Levine, PhD, the Barbara and Edward Netter Associate Professor in Cancer Gene Therapy in the department of Pathology and Laboratory Medicine and the director of the Clinical Cell and Vaccine Production Facility at Penn, used the ZFN technology to modify the T cells in the patientsa "molecular scissors," of sorts, to mimic the CCR5-delta-32 mutation. That rare mutation is of interest because it provides a natural resistance to the virus, but in only 1 percent of the general population. By inducing the mutations, the scientists reduced the expression of CCR5 surface proteins. Without those, HIV cannot enter, rendering the patients' cells resistant to infection.
For the study, the team infused the modified cells known as SB-728-Tinto two cohorts of patients, all treated with single infusionsabout 10 billion cellsbetween May 2009 and July 2012. Six were taken off antiretroviral therapy altogether for up to 12 weeks, beginning four weeks after infusion, while six patients remained on treatment.
Infusions were deemed safe and tolerable, the authors report, and modified T cells continued to persist in the patients when tested during follow up visits. One week after the initial infusion, testing revealed a dramatic spike in modified T cells inside the patients' bodies. While those cells declined over a number of weeks in the blood, the decrease of modified cells was significantly less than that of unmodified T cells during ADT treatment interruption. Modified cells were also observed in the gut-associated lymphoid tissue, which is a major reservoir of immune cells and a critical reservoir of HIV infection, suggesting that the modified cells are functioning and trafficking normally in the body.
The study also shows promise in the approach's ability to suppress the virus. The viral loads (HIV-RNA) dropped in four patients whose treatment was interrupted for 12 weeks. One of those patients' viral loads dropped below the limit of detection; interestingly, it was later discovered that the patient was found to be heterozygous for the CCR5 delta-32 gene mutation.
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Gene therapy locks out HIV, paving the way to control virus without antiretroviral drug
Gene therapy shows promise for HIV control without drugs: study-Eastday
WASHINGTON, March 5 -- U.S. researchers said Wednesday they have used gene therapy involving genetically engineered T- cells to successfully decrease the amount of the AIDS virus in several patients taken off antiretroviral drug therapy (ADT) entirely, including one patient whose levels became undetectable.
The study, published in the U.S. journal New England Journal of Medicine, is the first published report of any gene editing approach in humans, the researchers said.
"This study shows that we can safely and effectively engineer an HIV patient's own T cells to mimic a naturally occurring resistance to the virus, infuse those engineered cells, have them persist in the body, and potentially keep viral loads at bay without the use of drugs," senior author Carl June, professor of the University of Pennsylvania, said in a statement.
"This reinforces our belief that modified T cells are the key that could eliminate the need for lifelong ADT and potentially lead to functionally curative approaches for HIV/AIDS," June said.
In their study, the researchers used a technology called the zinc finger nuclease (ZFN) to modify the T cells in 12 patients with the AIDS virus in order to mimic the CCR5-delta-32 mutation that can provide a natural HIV resistance. Only one percent of the general population carries that rare mutation.
They then infused the modified cells known as SB-728-T into two groups of patients, all treated with single infusions of about 10 billion cells, between May 2009 and July 2012.
Six were taken off antiretroviral therapy altogether for up to 12 weeks, beginning four weeks after infusion, while six patients remained on treatment.
The researchers found that the amount of HIV dropped in four patients whose treatment was interrupted for 12 weeks.
One of those patients' viral loads dropped below the limit of detection before reinstitution of ADT and the patient was later found to be "heterozygous" for the CCR5-delta-32 gene mutation, they said.
"This case gives us a better understanding of the mutation and the body's response to the therapy, opening up another door for study," co-author Bruce Levine, associate professor of the University of Pennsylvania said.
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Gene therapy shows promise for HIV control without drugs: study-Eastday
Gene therapy may help control HIV
Scientists have modified genes in the blood cells of HIV patients to help them resist the AIDS virus, and say the treatment seems safe and promising.
The results give hope that this approach might one day free at least some people from needing medicines to keep HIV under control, a form of cure.
The idea came from an AIDS patient who appears cured after getting a cell transplant seven years ago in Berlin from a donor with natural immunity to HIV. Only about one per cent of people have two copies of the gene that gives this protection.
Researchers are seeking a more practical way to get similar results by using gene therapy to modify patients' own blood cells.
A study of this in 12 patients was led by Dr Carl June at the University of Pennsylvania with results publishedon Thursday in the New England Journal of Medicine. These are the first published results from this method, which also has been tried in several smaller studies of patients in California.
HIV usually infects blood cells through a protein on their surface, a 'docking station' called CCR5. A California company, Sangamo BioSciences, makes a treatment that can knock out a gene that makes CCR5.
The 12 HIV patients had their blood filtered to remove some of their cells. The gene-snipping compound was added in the lab, and the cells were infused back into the patients.
Four weeks later, half of the patients were temporarily taken off AIDS medicines to see the gene therapy's effect. The virus returned in all but one of them, but the modified cells seemed to be protected from HIV infection and were more likely to survive than the cells that had not been treated.
'We knew that the virus was going to come back in most of the patients,' but the hope is that the modified cells eventually will outnumber the rest and give the patient a way to control viral levels without medicines, said Dr Pablo Tebas, one of the Penn researchers. That would be what doctors call a 'functional cure,' because the virus would still be present but held in check without treatment.
The lone patient whose HIV did not return turned out to have one copy of the protective gene, so 'nature had done half of the job already,' Tebas said.
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