Public Workshop on Cell and Gene Therapy Clinical Trials in Pediatric Populations
The FDA will convene a one-day workshop (November 2, 2010 - 8:00 AM-5:30 PM) to facilitate an exchange of information about best practices in conducting cell and gene therapy clinical trials in pediatric populations. Cellular and gene therapies are the subject of great interest as novel products that potentially may improve the lives of patients by restoring lost function and modifying the nature and course of diseases. However, these therapies are not without risks: indeed, the novelty of these products contributes to their real and potential risks. Conducting clinical trials with novel products in pediatric patients requires special scrutiny to ensure that the rights of subjects are protected and that potential risks and benefits are appropriately balanced.
The purpose of the workshop is to gather information from Institutional Review Boards (IRBs), gene and cellular therapy clinical researchers, and other stakeholders regarding best practices related to cell and gene therapy clinical trials in pediatric populations, as well as challenges and considerations in the review of these clinical trials.
New Hope Against Melanoma
By taking a different approach, scientists have developed the next promising cancer treatment: targeted gene therapy. Skin cancer is scary, and it's tricky. If caught early it is easily treatable, but if not, it's potentially deadly. Even the best dermatologists can't spot everything. Targeted gene therapy is the latest treatment recognized by the New England Journal of Medicine. The new approach is proving fruitful when it comes to patients with the deadliest form of skin cancer: metastasized melanoma.
Gene Therapy to Treat Epilepsy a Step Closer
Current antiepileptic drugs (AEDs) have many side-effects, among others slowing down brain activity, which in turn reduces patients' ability to react. These side-effects could be eliminated if genes that counteract seizures could be introduced into the brain. Professor Merab Kokaia at Lund University in Sweden has obtained promising results in animal experiments.
CliniGene Competitive Call for Additional Project Partners
Programme title: CliniGene, (Contract number LSHB-CT-2006-018933), the European Network of Excellence for the Advancement of Clinical Gene Transfer and Therapy.
CliniGene seeks additional partners to enter its Joint Programme Activity on the topics:
Topic 1. Non-viral integrating systems for clinical gene therapy and development of human iPS, in particular transposon based technology;
Topic 2. AAV for in vivo gene therapy, in particular mechanisms leading to tight transcription regulation;
Topic 3. Technology transfer to SMEs for: (i) systems which have benefited from common evaluation and fine-tuning inside the NoE; (ii) a technology that is believed to complement the CliniGene current portfolio with view to performing side to side comparisons with gene transfer technologies already evaluated within CliniGene.
Study Shows Hope for Gene Therapy
Researchers have launched a new gene-therapy trial for children with a rare disease known as "bubble boy syndrome," reflecting fresh hopes that the strategy of delivering working genes can be used to treat many intractable ailments.
In the new study, sponsored in the U.S. by investigators at Children's Hospital Boston and expected to open at five sites around the world, scientists plan to enroll 20 boys with SCID-X1, which stands for severe combined immunodeficiency, X-linked—a genetic condition that affects boys and leaves them unable to fight germs. Without treatment, which is currently possible only by bone-marrow transplantation, most children die before age one.
A Step Closer to Gene Therapy for HIV
In a first step toward a gene-based therapy for HIV, researchers have successfully modified stem cells to resist the virus and used them to treat patients. Two years after the stem cells were used in a pilot study with four patients, descendants of those modified cells could still be found in their blood and bone marrow, along with some of the anti-HIV proteins the engineered cells were designed to produce, according to John Rossi, PhD, of City of Hope in Duarte, Calif., and colleagues.
Oncolytic vaccine therapy shows promise in melanoma, SCC studies
Efficacy and safety results of phase 2 studies provide support for undertaking pivotal trials investigating an oncolytic vaccine therapy, granulocyte colony-stimulating factor (GM-CSF)-encoding oncolytic herpes simplex virus (OncoVEXGM-CSF, BioVex), for treating metastatic melanoma (MM) and head and neck squamous cell carcinoma (SCC).
The herpes simplex virus on which OncoVEX-GM-CSF is based is genetically modified to replicate selectively in tumor cells and engineered to express a gene for GM-CSF, an immune-stimulating protein. The vaccine is injected into tumor deposits. As the virus replicates, it causes tumor cell lysis, leading to cell death and production of an immunogenic "soup" containing tumor antigens and GM-CSF. Through these mechanisms, the vaccine can eradicate the local tumor and serve as a vaccine matching each patient's tumor antigen profile that can induce a systemic immune response, which is, hopefully, sufficiently potent to eradicate tumor cells at distant, uninjected sites as well as to prevent future recurrences.
First-in-man gene therapy for advanced heart failure promising in small study
In the first clinical test of a gene therapy for heart failure, administration of a gene that upregulates an enzyme involved in myocardial contraction and relaxation appeared to improve symptoms, functional status, and ventricular volumes in patients with severe systolic heart failure. The small dose-finding study, reported here at the Heart Failure Congress 2010, sponsored by the Heart Failure Association of the European Society of Cardiology, is something of milestone and, its researchers say, paves the way for studying the novel treatment in larger clinical-outcomes trials.
Gene Therapy Reverses Muscle Weakness in MD
Patients with certain forms of muscular dystrophy (MD) may be able to achieve long-term restored muscle control with gene therapy, according to research presented Friday at the annual meeting of the American Society of Gene & Cell Therapy, held May 17 to 22 in Washington, D.C.
Following a successful trial that showed gene expression in patients three months after receiving a genetic transfer, Jerry R. Mendell, M.D., of Nationwide Children's Hospital in Columbus, Ohio, and colleagues conducted a randomized controlled trial of three patients with limb girdle MD (LGMD) in which the extensor digitorum brevis muscle received genetic therapy while the control side received saline to evaluate whether long-term gene expression was achievable.
Gene Therapy Plus Chemotherapy Ups Odds for Success in Treating 'Bubble Boy' Disease
Gene therapy combined with chemotherapy may lead to immune system improvement in patients with bubble boy disease, according to a study to be presented at the American Society of Gene & Cell Therapy 13th Annual Meeting.
Beginning in 2001, researchers from the University of California Los Angeles and the National Human Genome Research Institute, a division of the National Institutes of Health, treated 10 patients with adenosine deaminase severe combined immunodeficiency (ADA-SCID), commonly referred to as bubble boy disease.
‘Dead as Doornail’ Gene Therapy Revival Spurs Genzyme
Five years ago, doctors drilled a hole into Jean Erickson’s skull, pushed in a needle and injected a cold virus modified to help transport a gene into her brain. The gene’s job was to create a mini-factory within her brain cells to pump out dopamine, a chemical that regulates physical movement. Since then, Erickson has lived more comfortably with Parkinson’s disease, a disorder that robs patients of mobility. “I stopped freezing up,” said Erickson, 71, a former pre- school director who lives in Castro Valley, California.
New Gene Therapy Breakthrough in Humans is Result of Research Pioneered at OHSU's Primate Center
A promising gene therapy method first developed through animal studies at Oregon Health & Science University has now been successfully tested using human cells. Today, the scientific journal Nature published results of a study conducted at Newcastle University in the United Kingdom where a nucleus from one embryo was transferred to another.
It is believed that by using this method of gene transfer, genetic diseases carried in cell mitochondria might be prevented, and maternally-based diseases that are frequently passed from generation to generation could be halted.
UF-led effort creates virus reference standard that can improve patient safety in clinical trials
The use of viruses as vehicles for delivering genes to replace malfunctioning or missing ones holds promise for treating many disorders. Adeno-associated viruses are one type of vector being used increasingly in human gene therapy clinical trials and laboratory studies leading up to those trials. But differences in the way researchers determine the administered doses have made it difficult to accurately compare results from various studies.
Nanotech robots deliver gene therapy through blood
U.S. researchers have developed tiny nanoparticle robots that can travel through a patient's blood and into tumors where they deliver a therapy that turns off an important cancer gene. The finding, reported in the journal Nature on Sunday, offers early proof that a new treatment approach called RNA interference or RNAi might work in people.
Scientists Still Hopeful About Gene Therapy's Promise
Twenty-five years ago, it seemed as if gene therapy was on the verge of revolutionizing medicine. But that revolution never occurred, and scientists realized that they had been overly optimistic about how quickly they could develop such therapies. Now, however, there are signs that the field of gene therapy is making definite progress, even if the revolution is still on hold. The concept of gene therapy is simple. Some diseases are caused by damage to a single gene — for example, cystic fibrosis and hemophilia. Give patients the healthy gene, and in theory, the disease is cured.
Gene Therapy a Step Closer to Restoring Eyesight to Some Blind Patients
Researchers have moved a step closer toward fully restoring the eyesight of people with a rare genetic disorder. A new study shows the treatment is safe and effective, and could pave the way for helping cure more common causes of blindness. Leber's congenital amaurosis is an extremely rare condition that causes blindness in approximately 4,000 people in the United States.
Adeno-Associated Virus Type 2 Reference Standard Material is Now Available
The AAV2 vector reference standard material (an AAV2-GFP viral vector) is now available from ATCC (http://www.atcc.org). The AAV2 RSM is intended for use in calibrating internal (laboratory-specific) reference materials and assays for recombinant AAV viral gene transfer products, with the purpose of making data from different pre-clinical and clinical studies more comparable.
Amsterdam Molecular Therapeutics: EMA starts formal review of Glybera dossier
Amsterdam Molecular Therapeutics (Euronext: AMT), a leader in the field of human gene therapy, has reached another important milestone in the official marketing authorisation process for its lead product Glybera, AMT's proprietary product for lipoprotein lipase deficiency (LPLD). The submission of the Glybera Marketing Authorisation Application (MAA), announced earlier, has cleared the validation stage with The European Medicines Agency (EMA, formerly known as EMEA). The EMA will now commence its formal review of Glybera.
The EMA has published a Concept paper on the revision of the note for guidance on the quality, pre-clinical and clinical aspects of gene transfer medicinal products
The European Medicines Agency has published a Concept paper on the revision of the note for guidance on the quality, pre-clinical and clinical aspects of gene transfer medicinal products (EMA/CHMP/GTWP/BWP/234523/2009). This Concept Paper proposes a revision of the Note for Guidance on the Quality, Preclinical and Clinical Aspects of Gene Transfer Medicinal Products (CPMP/BWP/3088/99) that came into effect in 2001. This revision will address the issues identified from clinical experience and provision of Scientific Advice on gene therapy medicinal products and will lay down detailed and updated requirements for the quality, non-clinical and clinical aspects of gene therapy medicinal products.
Molecular Security System That Protects Cells from Potentially Harmful DNA Discovered
Researchers at the University of Minnesota have discovered a molecular security system in human cells that deactivates and degrades foreign DNA. This discovery could open the door to major improvements in genetic engineering and gene therapy technologies. Led by Reuben Harris, associate professor of biochemistry, molecular biology and biophysics in the College of Biological Sciences, the report's findings will be published online by Nature Structural and Molecular Biology on Jan. 10.
Oxford BioMedica Receives Orphan Designation for Gene Therapy Treatment for Stargardt Disease
Gene therapy developers, Oxford BioMedica (LSE: OXB) announced its StarGen therapy has received orphan treatment designation from the European Medicines Agency (EMEA). As a result the treatment will have ten years of marketing exclusivity and reduced regulatory fees. StarGen’s clinical development is expected to start in 2010, in collaboration with Sanofi-Aventis (NYSE: SNY). Stargardt Disease is a rare disease that causes cells on the macula area of the retina to stop working, which leads to problems with central vision. At first it makes vision unclear, distorted or blurred. After a longer period, Stargardt's can cause a ‘blank patch’ in the centre vision. There are currently no treatments available for Stargardt disease.
Gene Therapy Halts Brain Disease in Two Boys
Researchers have used a modified AIDS virus to halt a devastating brain disease in two young boys. The treatment, in which the virus delivered a therapeutic gene, marks the first time gene therapy has been successfully used against X-linked adrenoleukodystrophy (ALD)--a disorder that is always fatal if untreated. With this proof of principle, scientists hope versions of the AIDS virus engineered to carry different genes can now be applied to a variety of other diseases. ALD is caused by a defect in an X chromosome gene that produces a protein called ALD. Cells need this transporter protein to break down certain fats; without it, the fats build up and damage the myelin sheathing that protects nerves. In X-linked ALD, which strikes mainly boys, patients develop neurological symptoms such as seizures and loss of vision around age 6 to 8, and within months they become paralyzed, deaf, and eventually die.
For the first time, scientists in the McEwen Centre for Regenerative Medicine, University Health Network have successfully used gene therapy to repair injured human donor lungs, making them potentially suitable for transplantation into patients. This technique could significantly expand the number of donor lungs by using organs that are currently discarded, and improve outcomes after transplantation.
In their pioneering work, a team of researchers led by Dr. Shaf Keshavjee, Senior Scientist at the McEwen Centre for Regenerative Medicine, University Health Network and Director of the Lung Transplant Program, University Health Network developed a technique of ex vivo gene delivery to donor lungs, before they are implanted into a recipient's body. The technique was shown to be simple and effective in improving lung function.
Born with a retinal disease that made him legally blind, and would eventually leave him totally sightless, the nine-year-old boy used to sit in the back of the classroom, relying on the large print on an electronic screen and assisted by teacher aides. Now, after a single injection of genes that produce light-sensitive pigments in the back of his eye, he sits in front with classmates and participates in class without extra help. In the playground, he joins his classmates in playing his first game of softball.
Amsterdam Molecular Therapeutics (Euronext: AMT), a leader in the field of human gene therapy, announced today that the European Medicines Agency (EMEA) has granted Orphan Drug Designation to AMT's gene therapy product AMT-080 for the treatment of Duchenne muscular dystrophy.
Orphan Drug Designation for Duchenne muscular dystrophy (DMD) entitles AMT to ten year market exclusivity in Europe following marketing approval for AMT-080 if this product candidate is the first new drug with a major medical benefit receiving marketing approval for the European Union. The designation also provides for special benefits, including research support, eligibility for protocol assistance and possible exemptions or reductions in certain regulatory fees during development or at the time of application for marketing approval.
Scientists say they have used gene therapy to enable colorblind monkeys to see red and green, possibly opening the door to curing colorblindness in people. Jay Neitz of the University of Washington in Seattle and his colleagues injected gene-carrying viruses into the retinas of two male squirrel monkeys, which are naturally colorblind. The gene carried instructions for the production of a protein known as opsin, which makes pigments that are sensitive to the colors red and green. About five weeks after the treatment, the monkeys -- named Dalton and Sam -- began to develop the ability to see those colors, according to the results of detailed testing reported this week in the journal Nature.
For years, gene therapy produced tons of hype but no results. Recently, though, new approaches have yielded its first successes: breakthrough treatments for blindness, cancer, and the deadly bubble boy disease.
“For the first two years of her life, my daughter, Katlyn, was knocking on heaven’s door every day,” says Daisy Demerchant, a 26-year-old mom living in Centreville, New Brunswick, just north of Maine. “Two months after she was born she started getting sick, and she never got better.” At six months Katlyn was diagnosed with “bubble boy” disease, formally known as severe combined immunodeficiency (SCID), which robs the immune system of the ability to fight infection. There are many causes of this disorder; in Katlyn’s case it was lack of the enzyme adenosine deaminase, or ADA, which rids the body of a natural toxin called deoxyadenosine. When the toxin builds up, it destroys T and B lymphocytes, the body’s infection-fighting immune cells. As a result, Katlyn’s immune cells were dying.
A common antibiotic can function as an "off switch" for a gene therapy being developed for Parkinson's disease, according to University of Florida researchers writing online in advance of September's Molecular Therapy. The discovery in rats answers an important question — how can new, therapeutic genes that have been irrevocably delivered to the human brain to treat Parkinson's be controlled if the genes unexpectedly start causing problems? Meanwhile, in a review of Parkinson treatments, the researchers say that prior experimental attempts using growth factors — naturally occurring substances that cause cells to grow and divide — to rescue dying brain cells may have failed because they occurred too late in the course of the disease. Together, the findings suggest that gene therapy to enable the brain to retain its ability to produce dopamine, a neurotransmitter that falls in critically short supply in Parkinson's patients, could be safely attempted during earlier stages of the disease with an added likelihood of success.
The death of a young patient participating in a gene-therapy trial for a rheumatoid arthritis drug was most likely the result of another arthritis drug, adalimumab (Humira), and not the novel gene therapy agent, a new study found. "The death of this young patient who was receiving multiple forms of TNF inhibitors highlights the risk of opportunistic infections in patients receiving such agents, and the importance of having a well-designed monitoring plan when a patient in a study becomes ill," Karen M. Frank, MD, of the University of Chicago Medical Center, and colleagues wrote in the July 9 issue of New England Journal of Medicine.
The patient, a 35-year-old woman with a 15-year history of rheumatoid arthritis, first presented three days after receiving a second injection on July 2, 2007, of the active gene-therapy agent, tgAAC94, a tumor necrosis factor alpha (TNF-α) antagonist. She was suffering from a range of symptoms that including fever, chills, abdominal pain, and vomiting.
The National Institutes of Health Office of Biotechnology Activities (OBA) has been informed that a "relative clonal dominance" was detected during follow-up of a subject who is participating in a French human gene transfer trial being conducted for individuals with β-Thalassemia Major and Sickle Cell Anemia. The clinical trial, sponsored by Genetix France, used hematopoietic stem cells transduced by a self inactivating (SIN) HIV-1 lentiviral vector containing the gene for β-globin under the control of the β-globin promoter. The subject received the gene modified cells in June 2007.
This clonal dominance appears to result from the integration of the vector in the gene encoding for the HMGA2 protein, which is associated with both benign and malignant tumors. The clone however has been stable for five months and the subject remains in good health. In fact, although the subject required almost monthly blood transfusions during the 11 months prior to the gene transfer intervention, the subject has not since required a blood transfusion.