The basic physical and functional unit of heredity is the genes. It is a specific sequence of sources that programs instructions on how to produce proteins. Although genes gets a lot interest because of lack of open understanding of its nature, it is the protein that is the main element that perform most of life functions and even consists of the majority of the cellular structures. When the genes are changed, the programmed or encoded proteins become unable to accomplish the usual function expected from it and genetic disorders arise.

Gene therapy is the replacement of genetic material to an impaired cell. It then corrects the flaw in the genome of a patient. Gene therapy can also be applied to a developed lifetime disease of an individual such as cancer or recurring infection. It gives a specific trait or attribute to the cell giving it strength to combat the disease.

Generally, gene therapy is normally used in acute diseases when the cells of a particular organ in the body cannot function the normal way because it does not have sufficient required protein to perform a specific bodily task. In order to replace the faulty protein, a gene transfer vector or a gene transfer agent is altered so that it contains the gene that encodes for this protein. The altered vector is then administered to the patient. The gene transfer vector delivers the altered gene to the cell, which in turn, the cells mechanism converts the healing gene to correct the problem. In essence, it fixes the malfunctioning cell.

To summarize, gene therapy is a procedure for correcting defective genes that are responsible for the development of a disease. There are several approaches that maybe used in correcting faulty genes:

* The most common is the insertion of a normal gene into a non-specific location inside the genome to replace the non-functional gene.

* An abnormal gene is being substituted by a normal gene using homologous recombination or DNA crossover.

* The abnormal gene is repaired by undoing the genetic damage that happened long time ago. It is also called selective reverse mutation, which returns the gene to its normal function.

The gene transfer vector or a gene transfer agent, which is the carrier to deliver the therapeutic gene to the patients target cells is basically a virus that has been altered genetically to carry a normal human DNA. Many scientists tried to take advantage of this discovery and manipulate the virus genome to aid in delivering the healing genes and remove the disease causing ones.

Some of the few different types of viruses that are used as gene therapy vectors are retroviruses, adenoviruses, adeno-associated viruses and herpes simplex viruses.

There are also factors that have kept gene therapy from becoming the perfect treatment for genetic diseases. Some of the discovered factors are:

* Short life of gene therapy

* Immune response

* Risk of viral vectors that once inside the patients body, it may recover its ability to cause disease.

* Multigene disorders

Human gene therapy has triggered many issues since it was known. The promise of the technology is very great but the reality of it is somehow overwhelming. Human gene therapy must be seriously and cautiously evaluated.

It will be, as technology evolves.

Dave Kotecki is an innovative businessman who has a passion for new advancements in medical technology. His principle if you cant sell, youll fail is one of the benchmarks of his ability to practice what he learned in the internet industry. To learn how you can profit from the discovery of customized nutritional products, click here .

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How Helpful is Gene Therapy? - Good Herald

May 30, 2017 08:05 ET | Source: Abeona Therapeutics Inc

NEW YORK and CLEVELAND, May 30, 2017 (GLOBE NEWSWIRE) -- Abeona Therapeutics Inc. (Nasdaq:ABEO), a leading clinical-stage biopharmaceutical company focused on developing novel gene therapies for life-threatening rare diseases, announced today that the FDA has granted Rare Pediatric Disease Designation for Abeonas EB-101 gene therapy program for patients with dystrophic epidermolysis bullosa (DEB), including recessive dystrophic epidermolysis bullosa (RDEB), which are life-threatening genetic skin disorders characterized by skin blisters and erosions that cover the body.

These designations are granted to drugs with high promise that may address areas of unmet medical need for children with rare diseases. RDEB is a debilitating and life threatening inherited disorder with no approved treatment options available for patients today," stated Timothy J. Miller, Ph.D., President & CEO of Abeona Therapeutics Inc. Building upon the already granted FDA and EMA Orphan Drug Disease Designations for the EB-101 gene therapy program, receiving the Rare Pediatric Disease Designation is another important validation of the science and clinical approach to developing a novel gene therapy for RDEB patients.

Typically, wounds on patients with RDEB, also known as "butterfly skin" syndrome, can remain unhealed for months to years due to the inability of the skin to stay attached to the underlying dermis and can cover a large percentage of the body. In the ongoing Phase 1/2 clinical trial, EB-101 was administered to non-healing chronic wounds on each subject and assessed for wound healing at predefined time points over years. The primary endpoints of the clinical trial assess safety and evaluate wound healing after EB-101 administration compared to control untreated wounds. Secondary endpoints include expression of collagen C7 and restoration of anchoring fibrils at three and six months post-administration.

About Rare Pediatric Disease Designation: The rare pediatric disease designation indicates that the FDA may give the company a pediatric priority review voucher if the drug is approved for the pediatric indication. That voucher could then be used by the company for another drugany drugto be given a priority review. A priority review mandates that the FDA will review a BLA drug submission within six months instead of the standard 10 months. Normally, a priority review designation would only be given to a drug that is for a serious condition and has demonstrated the potential to be a significant improvement in safety and effectiveness. The priority review voucher may be used by the sponsor, sold or transferred.

EB-101 Gene Therapy Program Highlights:

About EB-101: EB-101 is an autologous, ex-vivo gene therapy in which COL7A1 is transduced into autologous keratinocytes for the treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB). RDEB is a subtype of an inherited genetic skin disorder characterized by chronic skin blistering, open and painful wounds, joint contractures, esophageal strictures, pseudosyndactyly, corneal abrasions and a shortened life span. Patients with RDEB lack functional type VII collagen owing to mutations in the gene COL7A1 that encodes for C7 and is the main component of anchoring fibrils, which stabilize the dermal-epidermal basement membrane. Patients are being enrolled in the ongoing Phase 2 portion of the Phase 1/2 clinical trial (NCT01263379). The EB-101 program has also been granted orphan drug designation by the FDA and European Medicines Agency (EMA).

About Epidermolysis Bullosa (EB): EB is a group of devastating, life-threatening genetic skin disorders that is characterized by skin blisters and erosions all over the body. The most severe form, recessive dystrophic epidermolysis bullosa (RDEB), is characterized by chronic skin blistering, open and painful wounds, joint contractures, esophageal strictures, pseudosyndactyly, corneal abrasions and a shortened life span. Patients with RDEB lack functional type VII collagen (C7) owing to mutations in the gene COL7A1 that encodes for C7 and is the main component of anchoring fibrils that attach the dermis to the epidermis. EB patients suffer through intense pain throughout their lives, with no effective treatments available to reduce the severity of their symptoms. Along with the life-threatening infectious complications associated with this disorder, many individuals often develop an aggressive form of squamous cell carcinoma (SCC).

About Abeona: Abeona Therapeutics Inc. is a clinical-stage biopharmaceutical company developing gene therapies for life-threatening rare genetic diseases. Abeona's lead programs include ABO-102 (AAV-SGSH), an adeno-associated virus (AAV) based gene therapy for Sanfilippo syndrome type A (MPS IIIA) and EB-101 (gene-corrected skin grafts) for recessive dystrophic epidermolysis bullosa (RDEB). Abeona is also developing ABO-101 (AAV-NAGLU) for Sanfilippo syndrome type B (MPS IIIB), ABO-201 (AAV-CLN3) gene therapy for juvenile Batten disease (JNCL), ABO-202 (AAV-CLN1) for treatment of infantile Batten disease (INCL), EB-201 for epidermolysis bullosa (EB), ABO-301 (AAV-FANCC) for Fanconi anemia (FA) disorder and ABO-302 using a novel CRISPR/Cas9-based gene editing approach to gene therapy for rare blood diseases. In addition, Abeona has a plasma-based protein therapy pipeline, including SDF Alpha (alpha-1 protease inhibitor) for inherited COPD, using its proprietary SDF (Salt Diafiltration) ethanol-free process. For more information, visit http://www.abeonatherapeutics.com.

Investor Contact: Christine Silverstein Vice President, Investor Relations Abeona Therapeutics Inc. +1 (212)-786-6212 csilverstein@abeonatherapeutics.com

Media Contact: Andrea Lucca Vice President, Communications & Operations Abeona Therapeutics Inc. +1 (212)-786-6208 alucca@abeonatherapeutics.com

This press release contains certain statements that are forward-looking within the meaning of Section 27a of the Securities Act of 1933, as amended, the expected receipt of a Priority Review Voucher and that involve risks and uncertainties. These statements include, without limitation, our plans for continued development and internationalization of our clinical programs, that patients will continue to be identified, enrolled, treated and monitored in the EB-101 clinical trial, and that studies will continue to indicate that EB-101 is well-tolerated and may offer significant improvements in wound healing. These statements are subject to numerous risks and uncertainties, including but not limited to continued interest in our rare disease portfolio, our ability to enroll patients in clinical trials, the impact of competition; the ability to develop our products and technologies; the ability to achieve or obtain necessary regulatory approvals; the ability to secure licenses for any technology that may be necessary to commercialize our products; the impact of changes in the financial markets and global economic conditions; and other risks as may be detailed from time to time in the Company's Annual Reports on Form 10-K and other reports filed by the Company with the Securities and Exchange Commission. The Company undertakes no obligations to make any revisions to the forward-looking statements contained in this release or to update them to reflect events or circumstances occurring after the date of this release, whether as a result of new information, future developments or otherwise.

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Abeona Therapeutics Receives Rare Pediatric Disease Designation ... - GlobeNewswire (press release)

Spark Therapeutics has posted fresh data from a phase 1/2 trial of its hemophilia B gene therapy, SPK-9001. The data suggest Sparks tapering courses of steroids successfully arrested the factor IX (FIX) declines seen in two patients who appeared to have an immune reaction to the Spark100 vector capsid.

Philadelphia-based Spark first reported on the two patients in December. At that time, the fall in FIX activityfrom 71% to 68% and, more dramatically, 32% to 12%raised concerns about the safety of the treatment. Spark downplayed these concerns, noting that the patient who received steroids more promptly only experienced a 3% decline in FIX activity. The latest set of data backed up Sparks confidence.

Both patients have now completed their tapering courses of steroids. After completing the courses of steroids, both patients saw their alanine aminotransferase levels return to baseline. The FIX activity of the subject whose level fell to 12% has since stabilized. Spark said the patient has been at around 15% over the nine weeks since finishing the course of steroids, a level likely to result in improved clinical outcomes. The other patients FIX activity is back up above 70%.

Our analysis suggests that a tapering course of oral corticosteroids has been well-tolerated and may help control potential capsid immune responses following SPK-9001 infusion, Spark CSO Katherine High, M.D., said in a statement.

Those data could lessen concerns that immune responses will scuttle the gene therapy, which has consistently delivered higher FIX activity levels than its main rival, uniQures AMT-060. UniQure sees safety as an area in which it may have an edge over Spark, although questionmarks hang over the elevated liver enzymes seen in some patients in the study.

Other aspects of the Spark data drop are free from red flags. Mean steady-stage FIX activity in the 10 participants who are 12 weeks or more post treatment stood at 33% at the last count. That is up on the 28% Spark reported in its December update. And with the range of responses spanning from 14% to 81%, it is also well clear of the 3% to 12.7% uniQure recorded in its high-dose cohort in December.

UniQure has argued FIX activity levels are less important than clinical benefits, such as cessation of bleeding and reduction in infusions. Sparks latest data show SPK-001 continuing to perform well against these measures. At the last count, the annualized bleeding rate was down 96%. The fall in the annualized infusion rate was 99%.

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Spark hemophilia B gene therapy clears another early test - FierceBiotech

Xconomy San Diego

Christopher Reinhard will tell you there is nothing unusual about the 20-plus years hes spent getting an experimental heart therapy to late-stage clinical trials.

Very rarely will you get a short story on development of a drug, said Reinhard (above), who is a principal investor and the CEO of San Diego-based Angionetics. Two decades is about what you would expect for a new drug-making method, Reinhard said.

That may be true, but it doesnt begin to convey the tortuous path that Reinhard has followed to get Angionetics where it is today. The biotech is starting a phase 3 trial in the next few months that seeks to enroll some 320 patients with myocardial ischemiawhen clogged coronary arteries reduce the flow of oxygen-rich blood to the heart.

To treat the disease, Angionetics isnt testing some new type of cholesterol-lowering drug, or a stent to help open clogged arteries.

Rather, its attempting a risky and less-proven methodgene therapy, in which new genetic instructions are transported into the body to help produce a specific protein. Gene therapies have been in development for decades, but are only now starting to come of age thanks to a variety of technological advances. Two therapies are approved in Europe, from UniQure (NASDAQ: QURE) and GlaxoSmithKline, both for ultra rare immune and metabolic diseases. Spark Therapeutics (NASDAQ: ONCE) this year is expected to file the first ever U.S. approval application for a gene therapy, a treatment for a form of childhood blindness.

Angionetics gene therapy, Ad5FGF-4 (Generx), is intended to stimulate the growth of new blood vessels in the heart. A catheter inserted through the groin delivers the genescarried within modified virusesinto heart cells, where they are supposed to produce a protein, fibroblast growth factor-4, that helps grow new blood vessels.

The hope is to ease chest pain and relieve the effects of clogged coronary arteries by stimulating the growth of new blood vessels in areas in the heart where there is insufficient blood flow. Were just taking the heart and trying to enhance its ability to grow more blood vessels, Reinhard said.

Angionetics image highlights growth of collateral blood vessels (Image by Bryan Christie Design, used with permission)

While gene therapies are more advanced than ever, and several experimental treatments aimed at heart disease and heart failure are being tested, none have yet succeeded. A heart failure gene therapy from San Diegos Celladon, for instance, failed in 2015.

Still, the potential prize is substantial. Of the estimated 16.5 million Americans with coronary heart disease, Angionetics Reinhard said about half experience heart-related chest pain.

The current standard of care offers two principal methods of treatment. The first course of therapy is usually to prescribe drugs like nitrates that temporarily dilates blood vessels to Next Page

Bruce V. Bigelow is the editor of Xconomy San Diego. You can e-mail him at bbigelow@xconomy.com or call (619) 669-8788

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Angionetics Nears Key Gene Therapy Trial for Coronary Heart Disease - Xconomy

New step toward the treatment of myotubular myopathy gene ... Science Daily A team of researchers has demonstrated the efficacy of administration of a therapeutic vector by a single intravenous injection and identified the dose that ... and more »

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New step toward the treatment of myotubular myopathy gene ... - Science Daily

Tocagen has filed to raise up to $86 million in an IPO to take its breakthrough-designated brain cancer gene therapy combination through the first part of a phase 2/3 trial. The San Diego, California-based biotech expects to deliver data from the phase 2 in the first half of next year, having wrapped up enrollment last month.

That trial is assessing the combination of gene therapy Toca 511 and prodrug Toca FC in patients with first or second recurrence of glioblastoma or anaplastic astrocytoma who are undergoing resection.

Subjects receive either standard of care or the Toca 511-Toca FC combination. Toca 511 is a retroviral replicating vector that encodes cytosine deaminase (CD). Its administration is intended to equip cancer cells to produce CD, a prodrug activator enzyme. Tocagen then gives patients the prodrug, Toca FC, an extended-release formulation of approved antifungal agent 5-fluorocytosine that is inactive until exposed to CD. Tocagen hopes Toca FC will cross the blood-brain barrier, be activated by CD and then kill both cancer cells and immunosuppressive cells.

Among the 24 patients who received the higher Toca 511 doses in a phase 1 and met the inclusion criteria for the phase 2/3, Toca saw three complete responses and two partial responses. At the time of the last data update, the responders were still alive 24 to 43 months after entering the study. The median overall survival for the 24 patients is 14.3 months.

The question facing Tocagen is whether that will translate into improved overall survival when the experimental regimen is pitted against standard of care options including Mercks Temodal and Roches Avastin. Tocagen is hoping Wall Street will provide the money it needs to start to answer the question.

Tocagen is yet to set the terms for its IPO, but listed $86 million as its proposed maximum offering. A chunk of the anticipated haul is earmarked for manufacturing scale-up and validation of Toca 511 and Toca FC. Tocagen plans to set aside another tranche to complete the ongoing phase 2, leaving some cash left over to wrap up a phase 1b of the combination in other indications, including newly-diagnosed brain cancer and a clutch of other solid tumors.

If Tocagen hits its fundraising goal, the IPO cash will see it through at least the next 12 months, taking it up to the delivery of phase 2 data.

Tocagen has financed its progress to date through a series of low-profile venture roundsmost recently a $28.8 million investment in 2015and by seeking donations via a brain cancer nonprofit.

Management must now persuade public investors to part with their cash. This year, Braeburn Pharmaceuticals and Visterra have both pulled IPOs after getting a frosty reception on Wall Street. Another company, ObsEva, hit its range but subsequently saw its stock slide. Tocagen will be hoping its experience has more in common with Jounce Therapeutics, which raised $102 million before seeing its stock go on a 30% tear in its first months on the market.

Jounce benefited from the starpower of a $2.6 billion pact with Celgene and a pitch that positions it at the forefront of the second wave of immuno-oncology. Tocagen lacks attributes with such pulling power, but in co-founder and R&D chief Harry Gruber, M.D. it has a name that could turn the heads of investors.

Gruber is gene therapy specialist who has played a role in getting a handful of biotechs started over the past 30 years, including Gensia and Viagene. Gensia ultimately became part of Teva through a $3.4 billion buyout, while Viagene accepted a $95 million bid from Chironnow part of Novartisafter a bumpy few years trying to develop gene therapies in the early 1990s.

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Tocagen seeks $86M IPO to fund cancer gene therapy trial ... - FierceBiotech

by Stuart Tomlinson, KATU News

Even before her first birthday, Kristin Kelly Bretanas parents noticed a fluttering in her eyes. As she grew, Bretana said she was accident-prone and had trouble seeing colors.

I have difficulty seeing far away, and I have difficulty with a lot of light saturation and Im almost completely color blind, Bretena said. And I say almost because there are certain situations where I can see a color if the saturations high enough.

Eventually her doctors gave her the news: She had achromatopsia, a rare genetic disease that results when you have a mutation in a gene that codes for a protein thats very important for the function of the cones.

To see, our retinas use rods and cones. Rods we use at nighttime and in dim light, cones are what we use during the daytime and for our color vision, says Dr. Mark Pennesi, OHSU Associate Professor of Ophthalmology whos now treating Bretana for the disease with gene therapy.

With achromatopsia the rods are actually ok, but the cones have no function at all," Pennesi said. "These patients have severe vision loss, theyre legally blind and they have no color vision at all. When they go outside they can barely see. They have to wear very dark sunglasses, but in dim light they actually see very well.

Pennesi said by taking a modified virus and stripping out all the things that make you sick, doctors then inject a normal copy of the missing or diseased gene back into the eye. The modified gene can then perhaps either stop the progression of the disease, or even restore function.

We actually go inside of the eye with a very, very fine needle and create a little pocket of fluid underneath the retina and inject that modified virus, Pennesi said. The virus then attaches to the retinal cells and inserts that DNA into the cells so they can start making the protein again.

Bretana said she has come to accept her limitations.

Its something I am not allowed to forget whether it be crossing the street and realizing that I am putting my life into a persons hands who is driving down the road because I cannot see inside the cab of a car, she said. It doesnt bother me nearly as much as it used to when I was a child and struggling with issues like self-identity and self-efficacy and what-not.

Pennesi said the therapy can be used for other diseases of the eye. OHSU currently has 7 gene therapy studies underway.

Its actually a very exciting time because many of these patients for decades have been told theres nothing that can be done, Pennesi said.

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OHSU gene therapy studies offer hope - and vision - to patients with eye disease - KATU

A number of recent headlines imply a recent case study just publishedproves that gene therapy has cured sickle cell diseasea genetic disorder that incurs tremendous pain, suffering and diminished life expectancy.

Due to such limited progress in management of this condition, this team of researcherstook samples from the bone marrow of a patient with severe diseaseUsing a lentiviral vector, they transferred an anti-sickling gene into the patients stem cellswhich get put back into the patient in the hope they will multiply and replace the cells made with the defective gene.

[T]he team concludes their patient had complete clinical remission with correction of hemolysis and biologic hallmarks of the disease. Furthermore, after fifteen months, the antisickling protein remained high at approximately 50% and the patient had no crises or hospitalizations. Before, the patient required regular transfusions.

ACSHs Senior Fellow in Molecular Biology, Dr. Julianna LeMieux, puts the promise of gene therapy into even greater context for this and other disease entities:This is an incredibly promising result, even with the obvious caveat that it is only one person. Sickle Cell is a disease that is ripe for genetic advances[T]his one success story is incredibly encouraging for the sickle cell community and for moving the field of curing diseases using genetic editing forward.

[The study can be found here.]

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:Did Gene Therapy Cure Sickle Cell Disease?

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Sickle cell cure? Patient in complete remission following gene therapy - Genetic Literacy Project

Pfizer has confirmed it assessing potential sites in North Carolina for a gene therapy production plant.

Reports in the US press suggested Pfizer is considering either expanding its existing facility in Sanford, North Carolina or building the plant at a site nearby.

Kim Bencker, head of communications at Pfizer Global supply, told us in an emailed statement We recently announced that were moving forward with scoping potential sites in Sanford for our new gene therapy site.

She added: This work is still in the preliminary stages and we arent able to share additional detail at this time.

The move follows a little over a year after the US drug manufacturer acquired Bamboo, a North Carolina-based gene therapy developer.

The deal included a recombinant Adeno-Associated Virus (rAAV) vector design and production technology, a Phase I candidate for Giant Axonal Neuropathy and a preclinical programme targeting Duchenne Muscular Dystrophy (DMD).

Pfizer also gained a 11,000sq ft gene therapy manufacturing facility in Chapel Hill that Bamboo bought from the University of North Carolina in 2016.

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Pfizer mulls sites for NC gene therapy plant year after Bamboo buy - BioPharma-Reporter.com

JaCeon Golden has only ever known the inside of hospitals. But the treatment hes receiving may have implications far beyond his as-yet isolated life.

Round-faced and big-eyed, with a perpetual pout that belies his sunny nature, he looks as healthy as any other 5-month-old. But JaCeon was born without a functioning immune system. Even the most banal of infections a cold, a diaper rash could be deadly.

Earlier this year, JaCeon became the first baby at UCSF Benioff Childrens Hospital at Mission Bay to undergo an experimental gene therapy treatment that, doctors hope, will nudge his body to build a new, robust immune system.

From right: Dannie Hawkins checks on her nephew Ja'Ceon Golden, who is being held by patient care assistant Grace Deng at UCSF Benioff Children's Hospital on Wednesday, March 8, 2017, in San Francisco, Calif. Golden, who is five months old, is diagnosed with severe combined immunodeficiency disease (SCID). He is a patient at UCSF, where he stays in a sterile room. The hospital is working on a new gene therapy treatment for SCID. Hawkins brought her nephew Golden from New Mexico for the experimental treatment.

From right: Dannie Hawkins checks on her nephew Ja'Ceon Golden, who...

So far, his results are promising. In a few weeks, JaCeons great aunt, whos also his guardian, hopes to introduce him to the world outside.

Am I going to see him smile when we walk out of here? Dannie Hawkins, 52, said with a glance at the baby, being fed from a bottle by a nurse wearing a gown and gloves. Hows he going to do in the free world?

It will be a while months, probably years before JaCeon is able to fully integrate with that wide world: go to school and birthday parties, ride a public bus, swim in a community pool. But that those activities may be in his future at all is extraordinary.

The treatment given to JaCeon is the result of decades of research into gene therapy that included a string of striking failures that led many doctors to abandon the pursuit altogether.

Gene therapy long had been considered a potential treatment for severe combined immunodeficiency disorder, or SCID, the condition JaCeon was born with, and some other genetic syndromes. The idea is to replace a single gene thats causing trouble.

Even as many doctors gave up on the promise of gene therapy, teams of stubborn scientists kept plugging away. And a few years ago, their experiments started to work, propelled by advances in the understanding of stem cells in this case, a type called hematopoietic stem cells that live in bone marrow and are responsible for generating blood and immune cells and improved methods of delivering genetic repairs.

JaCeon Golden is treated by patient care assistant Grace Deng (center) and pediatric oncology nurse Kat Wienskowski.

JaCeon Golden is treated by patient care assistant Grace Deng...

Now human gene therapy is being tested in trials at UCLA, where a team has treated 20 children with one type of SCID, and at UCSF in collaboration with St. Jude Childrens Research Hospital in Memphis. Both trials are funded by grants from the California Institute for Regenerative Medicine, the states stem cell agency, located in Oakland.

Researchers are studying similar therapies in hopes of curing genetic syndromes like sickle cell disease. And the stem cell agency is funding gene therapy research into potential treatments for HIV, brain cancer and Huntingtons disease, among others.

Gene therapy has been shown to work, the efficacy has been shown. And its safe, said Sohel Talib, a senior science officer at the state stem cell agency. The confidence has come. Now we have to follow it up.

JaCeon was born at a hospital in Las Cruces, N.M., and diagnosed with SCID just after birth as part of a standard newborn screening. He was flown to UCSF, one of a handful of facilities with expertise in SCID, when he was 3 weeks old. His great-aunt joined him about a month later, in November.

The immune disorder is commonly known as bubble baby disease, because until fairly recently kids born with it had to live in isolation, often in plastic bubbles in hospital rooms or their own homes to protect them from infections.

Babies born with SCID have a genetic mutation that leaves their immune system unable to develop disease-fighting cells. Without treatment, most will die within a year. Since the 1970s, some babies with SCID were cured with a bone-marrow transplant. But to be effective, a perfect match was required, almost always from a sibling, and only about a fifth of kids have such a match.

Ja'Ceon Golden is held by patient care assistant Grace Deng, as Deng bottle feeds Golden at UCSF Benioff Children's Hospital on Wednesday, March 8, 2017, in San Francisco, Calif. Golden, who is five months old, is diagnosed with severe combined immunodeficiency disease (SCID). He is a patient at UCSF, where he stays in a sterile room. The hospital is working on a new gene therapy treatment for SCID. Golden was brought from New Mexico for the experimental treatment.

Ja'Ceon Golden is held by patient care assistant Grace Deng, as...

The rest could undergo a bone marrow transplant from a partial match in JaCeons case, his great-aunt was one but even when that treatment was successful, kids were left with fragile immune systems that required constant maintenance with antibiotics and other boosts.

Gene therapy, though, may prove as effective as a bone marrow transplant from a perfect match.

The procedure starts with doctors harvesting stem cells from a babys own bone marrow, usually taken from the hip. In JaCeons case, his stem cells were sent in January to St. Jude in Memphis, where scientists are perfecting the gene-therapy delivery mechanism.

Sending away JaCeons stem cells was probably the most stressful time of my life, short of my own kids maybe being born, said Dr. Morton Cowan, the lead investigator of the UCSF trial, who has worked in SCID research for more than 30 years.

JaCeons stem cells were flown east over the first big weekend of major storms in California. Flights were being canceled around the clock, and doctors only had a window of about 36 hours to get the fresh cells to the labs in Memphis.

The trip was successful, but not without a hitch. After the cells were engineered and were being sent back to California, the material for a few heart-stopping hours got lost in the mail.

In a couple of months, Cowan said, he hopes to be able to do the gene-therapy delivery at UCSF labs, avoiding the travel headaches.

For now, that still happens at St. Jude. Doctors used a virus in fact, HIV, the virus that causes AIDS to deliver the gene therapy to JaCeons stem cells. The virus is neutered, with all of the disease-causing pieces inside removed.

Whats left is a missile-like shell designed to infiltrate a cell and deliver whatever payload doctors have inserted inside in this case, a healthy gene that will restore the stem cells ability to build normal immune cells.

Back in San Francisco, the cells were infused into JaCeon via a port in his chest. Because theyre his own cells, there was no fear his body would reject them.

He did have to undergo mild chemotherapy to kill off some of his own bone marrow and make room for the re-engineered stem cells to roost, but UCSF has been developing a technique for limiting the dosage of chemotherapy given in gene therapy procedures.

JaCeon suffered no obvious side effects from either the stem cell infusion or the chemotherapy drugs, doctors said.

Hes just thriving. Hes just hes great, Cowan said. He added, We cant open the Champagne just yet, but early tests show the new gene is active, and JaCeon has had an uptick of certain immune cells.

The infusion procedure took just 20 minutes, and JaCeon slept through it, but it felt momentous nonetheless.

It had been difficult to decide to enroll JaCeon in the trial, Hawkins said. Since she was a partial match for a bone marrow transplant, she had the option of giving him the traditional and well-tested therapy.

Shed said to his doctors, So youre telling me hes a guinea pig? They told her, she recalls, If it works, he can open the door for other kids.

That night, as Hawkins slept on the decision, I kept waking up, waking up, all night long, she said. If there was a possibility he could save someone else ... she added, and then broke off in tears.

She spends about six hours with JaCeon every day, beginning each morning with a bath in sterile water, brought by nurses in special tubs. Shes constantly wiping down his toys, clothes, bedding and stuffed animals.

Ive changed a lot of diapers in my time, but this is way more complicated than with other kids, Hawkins said, demonstrating the multistep process she uses to prevent diaper rash.

Im not going to say its been easy, she said. But hes doing fine. I wouldnt have it any other way.

Erin Allday is a San Francisco Chronicle staff writer. Email: eallday@sfchronicle.com

Twitter: @erinallday

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Amid advances in gene therapy, 'bubble baby' in SF gains hope - San Francisco Chronicle

Pfizer has confirmed it assessing potential sites in North Carolina for a gene therapy production plant.

Reports in the US press suggested Pfizer is considering either expanding its existing facility in Sanford, North Carolina or building the plant at a site nearby.

Kim Bencker, head of communications at Pfizer Global supply, told us in an emailed statement We recently announced that were moving forward with scoping potential sites in Sanford for our new gene therapy site.

She added: This work is still in the preliminary stages and we arent able to share additional detail at this time.

The move follows a little over a year after the US drug manufacturer acquired Bamboo, a North Carolina-based gene therapy developer.

The deal included a recombinant Adeno-Associated Virus (rAAV) vector design and production technology, a Phase I candidate for Giant Axonal Neuropathy and a preclinical programme targeting Duchenne Muscular Dystrophy (DMD).

Pfizer also gained a 11,000sq ft gene therapy manufacturing facility in Chapel Hill that Bamboo bought from the University of North Carolina in 2016.

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Pfizer scopes out sites for gene therapy plant in North Carolina - BioPharma-Reporter.com

The human heart has an innate capacity to remodel in response to advancing coronary artery disease. As plaque builds up in the hearts three major arteries, some genetically privileged patients begin to grow small collateral blood vessels to overcome restricted blood flow and improve cardiac perfusion. This process is known as cardiac angiogenesis. With the passage of time, this response is overrun by disease progression.

Researchers have long wondered if this primal angiogenic healing response could be amplified and regulated through the design and development of angiogenic therapeutics. In recent years, monoclonal antibody therapies have proven effective at harnessing the human bodys natural biological mechanisms to treat cancer. Similarly, within cardiac care, angiogenic gene therapy has shown great promise.

In the U.S., more than one million patients with advanced coronary artery disease suffer from recurrent and severe chest pain, which profoundly limits their physical activity and quality of life. These refractory angina patients are no longer responsive to anti-anginal medications and are either not candidates for stent implantation or bypass surgery, or continue to suffer from angina even after these mechanical revascularization procedures. While drug and proteins appear unsuitable, new research and clinical studies focused on angiogenic gene therapy are now showing great promise as a one-time treatment for more than one million patients in the U.S. with advanced coronary artery disease and refractory angina.

The successful commercialization of an angiogenic gene therapy will require (1) an angiogenic growth factor that regulates the multiple proteins required to orchestrate micro-vessel growth and enlargement; (2) a simple percutaneous catheter-based delivery system to deliver the angiogenic gene therapy into heart cells; and (3) a deep understanding and characterization of patients who are most likely to benefit from angiogenic gene therapy, enabling design of a clinical study properly powered to detect treatment effects and assess potential risk-benefit.

Choice of Angiogenic Growth Factor

One key element of successful gene therapy is gene expression in the targeted cells, at a functional level. For angiogenic gene therapy, a central challenge has been identifying the growth factors that can stimulate the complex angiogenic biological process. It has been debated and widely studied whether the delivery of vascular endothelial growth factor (VEGF) or other growth factors, alone or in combination, is ideal for collateral vessel development. Recent research suggests a more fruitful approach may be the use of a specific regulatory gene, FGF-4, that is now known to activate VEGFs and the cascade of events required to stimulate cardiac angiogenesis. Using a regulatory gene is likely more practical than trying to determine which individual growth factor or growth factor combination is best suited for the job.

Simplified Catheter-Based Delivery Options

Even with firm understanding of the merits of individual angiogenic growth factors, a separate question remains: Which DNA delivery system is best suited for cardiovascular angiogenic gene therapy?

Advances have come with a key realization: the facilitation of coronary collateral formation requires a relatively short duration of gene expressiononly a few weeks. Vector systems that meet this requirement include plasmid constructs and adenovirus. So here was the next challenge: determining which of these two approaches was optimal. Plasmids are easy to manufacture and safe but have very low level and short duration of muscle transduction and could be delivered to the heart mainly through direct intramuscular injections. Adenoviral vectors, on the other hand, can be administered via the intravascular route and have been shown to achieve high transfection efficiency in heart muscle cells with transgene expression lasting for two to six weeks. The relatively short duration of growth factor gene expression by the adenovirus serotype 5 (Ad5) vector has proved sufficient for the building of new functional biological structures such as coronary collateral vessels.

Studies have demonstrated that fibroblast growth factor-4 (FGF-4) can promote the growth of existing or new collateral vessels in the heart, when delivered as a gene within an Ad5 vector. The resulting molecular packagenamed Ad5FGF-4is delivered into the heart as a one-time treatment during a standard angiogram-like procedure. The biologic is delivered in front of a balloon that briefly blocks blood flow, allowing the treatment to more easily leave the blood vessel and enter the cardiac muscle. FGF-4 gene expression promotes the development of new collateral vessels and the enlargement of existing collateral vessels in ischemic areas of the heart, to increase blood flow to these oxygen-starved regions.

Effective Clinical Study Design

An additional hindrance to historical progress in cardiovascular gene therapy may have involved study design. The standard endpoint used in most cardiovascular therapeutic angiogenesis studiese.g., exercise tolerance testing (ETT)is based on decades of experience with clinical development of small molecule anti-anginal drugs, and is still considered by regulatory authorities to be a relevant indicator of clinical effectiveness. In general, clinically significant improvements in ETT time resulting from mechanical revascularization (bypass surgery and stents), pharmacologic interventions or gene therapy, represent improved functional capacity for treated patients. ETT is known to be subject to placebo effect, and therefore careful study design, including well-defined patient inclusion criteria (e.g. limited baseline ETT capacity) and controlled testing conditions and criteria are essential for meaningful outcomes.

An attempt to fuse the insights and overcome the roadblocks summarized above are fueling ongoing efforts to improve and advance angiogenic gene therapy. Future studies are likely to elucidate the most promising therapies for cardiovascular angiogenic gene therapy and offer hope to the many patients for whom angina is currently a source of deep concern causing significant negative impact on quality of life.

Christopher J. Reinhard is Chief Executive Officer of Angionetics Inc., a company focused on the late-stage clinical development and commercialization of Generx, an angiogenic gene therapy product candidate designed for medical revascularization for the potential treatment of patients with myocardial ischemia and refractory angina due to advanced coronary artery disease.

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Angiogenic Gene Therapy for the Heart: Overcoming the Roadblocks - Drug Discovery & Development

Pfizer, which scooped up Bamboo Therapeutics last year in its aim to be a major player in gene therapies, is now looking at building a gene therapy production facility in North Carolina where the biotech is based.

Pfizer spokeswoman Kimberly Becker confirmed a report by the Triangle Business Journal that the company has been exploring the area. The newspaper was told by sources that Pfizer has talked to state and local officials about a potential $100 million expansion project. Bamboo is based inChapel Hill.

We recently announced that were moving forward with scoping potential sites in Sanford for our new gene therapy site. This work is still in the preliminary stages and we arent able to share additional detail at this time, Becker said in an email.

The sources told the newspaper thatPfizer also is considering putting it in Massachusetts. The drugmakercurrently is erecting a $200 million biologics and vaccines production facility at its campus in Andover.

But Bamboo already has an 11,000-square foot, fully staffed and operational manufacturing facility in Sanford it acquired last year from the University of North Carolina about the time that Pfizer made an initial investment in the company. Bamboo has produced phase I and II materials using a in the facility using what Pfizer said was superior suspension, cell-based production platform that increases scalability, efficiency and purity.

Pfizer last year bought Bamboo in two-step deal, laying out $193 million to acquire its stock, with a pledge of up to $495 million more in milestones. With gene therapies, genetic material is introduced into a patients body to replace gene mutations that cause disease.

The biotech is working on recombinant adeno-associated virus (rAAV)-based gene therapies for rare diseases. It has a pre-clinical asset for Duchenne Muscular Dystrophy (DMD); and three targeted at the central nervous system, with pre-clinical assets for Friedreichs Ataxia and Canavan disease, and a Phase I asset for Giant Axonal Neuropathy, Pfizer said.

Pfizer first entered the emerging field in 2014 with a deal with Spark Therapeutics in hemophilia. At that time, the company also established a dedicated gene therapy research center in London known as the Genetic Medicines Institute which falls under its Rare Disease Research Unit.

While the field offers the hope of one-time cures by dealing with the genetic root cause of a disease, it offers challenges for insurance coverage and payments. There have been no gene therapies approved yet in the U.S., but Dutch company uniQure developed the firstgene therapy approved in Europe, a treatment thathas been termed the worlds most expensive drug.

Approved in 2012, Glybera is priced at more than $1.2 million. Only one German doctor has been able to win insurance approval, despite the fact the treatment can cure the ultra-rare disease called lipoprotein lipase deficiency. uniQure is now focused on a hemophilia B program, competing with the gene therapy being developed by Spark Therapeutics with Pfizer.uniQure, which has had to eliminatejobs to cut costs, has a $25 million, 55,000-square-foot gene therapy manufacturing facility in Lexington, Massachusetts.

GlaxoSmithKline has also won approval in Europe for Strimvelis, its gene therapy for bubble boy disease. It is offering the one-time treatment at about $665,000, with a money-back guarantee.

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Pfizer looks at building major gene therapy manufacturing facility in ... - FiercePharma

A number of recent headlines imply a case study just published in the New England Journal of Medicine proves that gene therapy has cured sickle cell diseasea genetic disorder that incurs tremendous pain, suffering and diminished life expectancy. Here, we will unpack the significance of the researchers findings.

First, lets address why this news could be so groundbreaking to those afflicted and their loved ones.

Sickle Cell Disease is an inherited condition that causes a mutated hemoglobinthe protein within red blood cells (RBCs) that carries oxygen for delivery to vital tissues. Oxygen feeds our organs so they can stay healthy and perform their respective jobs. This Hemoglobin S (aka Sickle Hemoglobin) polymerizes on deoxygenation and rids the RBCs of their malleability. As a result, these malformed sickled cells are stiff and clump together thereby occluding vessels which in turn prompts organ damage.

Roughly 90,000 Americans have Sickle Cell Disease. (1) The natural course of the illness involves a complex cascade of events intermingled with crises often triggered by infections. Anemia is commonplace (and often profound) given these faulty cells get readily destroyed, over consumed and dont last as long as healthy RBCs. Vasoocclusive Crises result from infarction and ischemiain infants the hands and feet swell, in particular. Basically, adequate blood flow is halted wherever the obstruction takes place. Aggressive pain management and rehydration is essential.

Prophylactic antibiotics are a mainstay in an effort to stave off infection which can routinely catapult patients into a life-threatening crisis. By early childhood, they develop a functional asplenia or ineffective spleen. So, they become especially susceptible to overwhelming infection by encapsulatedbacteriahence, why vaccination for pneumococcus and the like is so important. Sepsis can result. Parvovirus can cause an aplastic crisis.

Strokes. Pulmonary infarcts with subsequent hypoxia. Acute Chest Syndrome. Gallstones. Blood transfusions are frequent. Though the blood supply is well-tested for safety, recurrent transfusion can lead to issues like iron overload, for instance. This too must be treated. The list goes on of the challenges, battles and treatment complexities these patients endure. Because fetal hemoglobin has a higher oxygen carrying capacity, a disease-modifying drug like Hydroxyurea that increases its presence is used.

Allogeneic hematopoietic stem-cell transplantation represents the only cure, but less than 18% of those with severe disease have sibling donors who are a match. (2) This is also not without great risk, though those need to be weighed against how advanced the disease. Due to such limited progress in management of this condition, this team of researchers sought to examine whether therapeutic ex vivo gene transfer into autologous hematopoietic stem cells referred to as gene therapy, may provide a long-term and potentially curative treatment for sickle cell disease. (3)

What does this mean? They took samples from the bone marrow of a patient with severe disease. The cells here provide the origins of our blood components which includes our red blood cells. This is where the problem begins in generating the sickling. A cancer drug, busulfan, was used to condition the body expected adverse effects from this occurred which resolved with standard care (e.g. anemia, low platelets, neutropenia and so on). Using a lentiviral vector, they transferred an anti-sickling gene into the patients stem cells (retrieved from the bone marrow) which get put back into the patient in the hope they will multiply and replace the cells made with the defective gene.

In a study funded in part by Bluebird Bio whose product is LentiGlobin BB305 (the antisickling gene therapy subject of this publication), the team concludes their patient had complete clinical remission with correction of hemolysis and biologic hallmarks of the disease. Furthermore, after fifteen months the antisickling protein remained high at approximately 50% and the patient had no crises or hospitalizations. Before, the patient required regular transfusions. After, all medications were stopped, no pain ones were needed, and the patient returned to full activities at school. (4)

Ongoing research is underway in a U.S. multi center, phase 1/2 clinical study. The intention is to use this gene therapy to treat those with severe sickle cell disease and another condition called beta-thalessemia. So far, in the few patients who have participated, their results seemingly support this work. Clearly, longer term follow-up and larger populations are crucial to understanding the significance of this report. Additionally, stem cell transplantation is no minor feat.

That said, for a disease that disables at such a young age, this option could be quite an extraordinary one if the success persists. ACSHs Senior Fellow in Molecular Biology, Dr. Julianna LeMieux, puts the promise of gene therapy into even greater context for this and other disease entities:"This is an incredibly promising result, even with the obvious caveat that it is only one person. Sickle Cell is a disease that is ripe for genetic advances for a few reasons. First,the gene that is affected is known andcan be replaced by the healthy variant. Also, the cells that are needed to be alteredare easily accessible inthe bone marrow. In many diseases, this is not the case. But, this one success story is incredibly encouraging for the sickle cell community and for moving the field of curing diseases using genetic editing forward."

The team proved their concept. To know if "cure" is in this gene therapy's future, much more data needs to be acquired and study be implemented. Promising with cautious optimism might be the most apt description.

Source(s):

(1) (2) (3) (4) Jean-Antoine Ribeil, M.D., Ph.D. et al. Gene Therapy in a Patient with Sickle Cell Disease. N Engl J Med. 376;848-855. March 2, 2017.

Note(s):

To learn more about "Orphan Diseases" or rare ones that afflict less than 200,000 (but in total impact 25 million Americans) and drug discovery challenges, review: Did Pompe Disease Geta New Champion in President Trump? and Pompe Disease, Newborn Screening and Inborn Errors of Metabolism.

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Did Gene Therapy Cure Sickle Cell Disease? | American Council on ... - American Council on Science and Health

This 2009 colorized microscope image made available by the Sickle Cell Foundation of Georgia via the Centers for Disease Control and Prevention shows a sickle cell, left, and normal red blood cells of a patient with sickle cell anemia.

Janice Haney Carr, AP

A French teen who was given gene therapy for sickle cell disease more than two years ago now has enough properly working red blood cells to dodge the effects of the disorder, researchers report.

The first-in-the-world case is detailed in Thursdays New England Journal of Medicine.

About 90,000 people in the U.S., mostly blacks, have sickle cell, the first disease for which a molecular cause was found. Worldwide, about 275,000 babies are born with it each year.

Vexing questions of race and stigma have shadowed the history of its medical treatment, including a time when blacks who carry the bad gene were urged not to have children, spurring accusations of genocide, Keith Wailoo of Princeton University wrote in a separate article in the journal.

The disease is caused by a single typo in the DNA alphabet of the gene for hemoglobin, the stuff in red blood cells that carries oxygen. When its defective, the cells sickle into a crescent shape, clogging tiny blood vessels and causing bouts of extreme pain and sometimes more serious problems such as strokes and organ damage. It keeps many people from playing sports and enjoying other activities of normal life.

A stem cell transplant from a blood-matched sibling is a potential cure, but in the U.S., fewer than one in five people have a donor like that. Pain crises are treated with blood transfusions and drugs, but theyre a temporary fix. Gene therapy offers hope of a lasting one.

The boy, now 15, was treated at Necker Childrens Hospital in Paris in October 2014. Researchers gave him a gene, taken up by his blood stem cells, to help prevent the sickling. Now, about half of his red blood cells have normal hemoglobin; he has not needed a transfusion since three months after his treatment and is off all medicines.

Its not a cure but it doesnt matter, because the disease is effectively dodged, said Philippe Leboulch, who helped invent the therapy and helped found Bluebird Bio in Cambridge, Massachusetts, the company that treated the boy. The work was supported by a grant from the French governments research agency.

Bluebird has treated at least six others in the U.S. and France. Full results have not been reported, but the gene therapy has not taken hold as well in some of them as it did in the French teen. Researchers think they know why and are adjusting methods to try to do better.

Two other gene therapy studies for sickle cell are underway in the U.S. -- at the University of California, Los Angeles and Cincinnati Childrens Hospital - and another is about to start at Harvard and Boston Childrens Hospital using a little different approach.

This work gives considerable promise for a solution to a very common problem, said Dr. Stuart Orkin, a Boston Childrens Hospital doctor who is an inventor on a patent related to gene editing.

The results are quite good in this patient, he said of the French teen. It shows gene therapy is on the right track.

2017 The Associated Press. All Rights Reserved. This material may not be published, broadcast, rewritten, or redistributed.

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Gene therapy lets a French teen dodge sickle cell disease - CBS News

I agree with Mr Darius Lee (Gene editing will create more divisions in society; March 3) that gene editing should not be used to promote eugenics.

However, gene editing to cure or ameliorate genetic diseases should be viewed as a form of medical advancement, akin to any medical breakthrough in the form of drugs or surgery.

Recently, it was reported that a teenage boy with sickle-cell anaemia was cured of the disease using gene therapy.

Presently, such patients are treated with blood transfusions to clear the blockages caused by abnormal haemoglobin, and have to be on powerful painkillers to manage the painful symptoms. Bone marrow transplants are also used to treat the disease, but finding matching donors can be difficult.

Many other genetic illnesses also exact a grave personal and financial toll on patients and their families.

Besides improving the quality of life for sufferers, gene therapy may also prove to be much less costly in the long term, as sufferers do not need to undergo further treatment.

It can be argued that gene therapy may be accessible only to patients in well-developed medical systems, thus potentially exacerbating the divisions between the "haves" and "have-nots".

But, just as we do not use this as a reason to withhold conventional medical treatment, so we should not condemn those with hereditary illnesses to life-long suffering if gene therapy is available to them.

It behooves society to make such treatments accessible to as many as people possible.

We may also already be"editing" our children's genetic potential with our lifestyle and behavioural choices, such as diet and smoking, as these factors may cause epigenetic modifications.

Studies have found that men who were smokers from an early age had sons who were significantly fatter than average.

Researchers who analysed historical records from a remote part of Sweden found that people whose grandparents had been short of food between the ages of nine and 12 seemed to live longer.

Whether intentionally or not, people have been subjected to varying forms of genetic modifications since time immemorial.

It is only right that gene editing be viewed as just another form of medical treatment to cure illnesses.

Maria Loh Mun Foong (Ms)

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View gene therapy as a medical advancement - The Straits Times

Researchers at Stanford have made mice glow using a new gene therapy technique, showing that the process can work on living animals.

(Courtesy of Linda Cicero).

Named charge-altering releasable transporters (CARTs), the new technique allows researchers to control how much of a desired protein is expressed inside a cell, and how long the gene therapy lasts. It has a variety of applications to many central problems in biology and medicine, including immunology and cancer research.

Previous gene therapy techniques have relied on permanently changing the DNA within a cell. Colin McKinlay, a third-year Ph.D. student in chemistry and co-lead author on the paper, explains that CARTs take advantage of messenger RNA (mRNA) rather than DNA to give researchers greater control over the process.

By introducing mRNA into the cells, you can basically tell those cells to produce any given protein, McKinlay said. Its more of a temporary effect and you have a lot more control over doing that.

However, mRNA molecules are too large to enter the cell on their own. CARTs are able to latch onto the mRNA, cross the cell membrane, release the mRNA into the cell and quickly degrade into small molecules called metabolites naturally recognizable by the cell. After that, the cell takes over, translating the mRNA into the desired proteins.

Its kind of like the cell already has all of the ingredients, McKinlay said. Were just providing the recipe, and the cell then puts all the pieces together.

One possible application of the new gene therapy technique is creating new types of vaccinations. Typical vaccination techniques involve introducing a dead or weakened antigen, bacteria and foreign substances such as viruses into the cell, which the body then uses to create antibodies. CARTs could allow researchers to temporarily introduce specific proteins from the antigens into cells in order to specify targets for the immune system that are less sensitive to antigen mutation.

CARTs also have the potential to be used as a research tool. As transient polycations, CARTs allow proteins to be introduced and manufactured by the cell in controlled quantities and for a controlled amount of time, making them a valuable resource for studying signaling cascades and other biological phenomena.

The team behind CARTs primarily consists ofWender and Waymouth Group researchers, andalso drawson collaborators across Stanford. As the team begins to test the potential applications of CARTs, more researchers are expected to come on board.

In their recent paper on bioluminescent proteins in mice, researchers worked with Christopher Contag, a professor of pediatrics at Stanford, to show that the technique can work in vivo in animal models,bringing the team a step closer to using it in humans.

We couldnt have done it if we were stuck just within the confines of the chemistry department, said Jessica Vargas 16, a formerPh.D. student in the Wender Lab and a co-lead author on the paper. The work in general is a true testament to Stanfords collaborative spirit.

Contact Aulden Foltz at afoltz at stanford.edu.

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Researchers develop controllable gene therapy, make rats glow ... - The Stanford Daily

An experimental gene therapy that turns a patients own blood cells into cancer killers worked in a major study, with more than one-third of very sick lymphoma patients showing no sign of disease six months after a single treatment

In all, 82 percent of patients had their cancer shrink at least by half at some point in the study.

Its sponsor, California-based Kite Pharma, is racing Novartis AG to become the first to win approval of the treatment, called CAR-T cell therapy, in the U.S. It could become the nations first approved gene therapy.

A hopeful sign: the number in complete remission at six months 36 percent is barely changed from partial results released after three months, suggesting this one-time treatment might give lasting benefits for those who do respond well.

The therapy is not without risk. Three of the 101 patients in the study died of causes unrelated to worsening of their cancer, and two of those deaths were deemed due to the treatment.

It was developed at the governments National Cancer Institute and then licensed to Kite. The Leukemia and Lymphoma Society helped sponsor the study.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post: Gene therapy to fight a blood cancer succeeds in major study

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One third of lymphoma patients cancer free after 6 months in CAR-T ... - Genetic Literacy Project

Gene therapy is the use of DNA as a potential therapy to treat a disease.In many disorders, particularly genetic diseases caused by a single genetic defect, gene therapy aims to treat a disease by delivering the correct copy of DNA into a patients cells.The healthy, functional copy of the therapeutic gene then helps the cell function correctly.

In gene therapy, DNA that encodes a therapeutic protein is packaged within a vector, often a naked virus, which is used to transfer the DNA to the inside of cells within the body. Gene therapy can be delivered by a direct injection, either intravenously (IV) or directly into a specific tissue in the body, where it is taken up by individual cells. Once inside cells, the correct DNA becomes expressed by the cell machinery, resulting in the production of therapeutic protein, which in turn treats the patients disease and can provide long-term benefit.

Abeona is developing next generation adeno-associated virus (AAV) gene therapies. Viruses such as AAV are utilized because they have evolved a way of encapsulating and delivering one or more genes of the size needed for clinical application, and can be purified in large quantities at high concentration. Unlike AAV vectors found in nature, the AAV vectors used by Abeona have been genetically-modified such that they do not replicate. Although the preclinical studies in animal models of disease demonstrate the promising impact of AAV-mediated gene expression to affected tissues such as the heart, liver and muscle, our programs use a specific virus that is capable of delivering therapeutic DNA across the blood brain barrier and into the central nervous system (CNS), making them attractive for addressing lysosomal storage diseases which have severe CNS manifestations of the disease.

Lysosomal storage diseases (LSD) are a group of rare inborn errors of metabolism resulting from deficiency in normal lysosomal function. These diseases are characterized by progressive accumulation of storage material within the lysosomes of affected cells, ultimately leading to cellular dysfunction. Multiple tissues ranging from musculoskeletal and visceral to tissues of the central nervous system are typically involved in disease pathology.

Since the advent of enzyme replacement therapy (ERT) to manage some LSDs, general clinical outcomes have significantly improved; however, treatment with infused protein is lifelong and continued disease progression is still evident in patients. Thus, viral gene therapy may provide a viable alternative or adjunctive therapy to current management strategies for LSDs.

Our initial programs are focused on LSDs such as Mucopolysaccharidosis (MPS) IIIA and IIIB, also known as Sanfilippo syndromes type A and type B. MPS III is a progressive neuromuscular disease with profound CNS involvement. Our lead product candidates, ABO-101 and ABO-102, have been developed to replace the damaged, malfunctioning enzymes within target cells with the normal, functioning version.

Delivered via a single injection, the drug is only given once.

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Gene Therapy - Abeona Therapeutics

In a world first, a teenager with sickle cell disease achieved complete remission after an experimental gene therapy at Necker Childrens Hospital in Paris, researchers say.

People with sickle-cell disease, a group of inherited blood disorders, have abnormal hemoglobin in their red blood cells, causing blood to clog in the tiny vessels and organs of the body.

After 15 months since treatment, the patient who began therapy at age 13 no longer needs medication, and his blood cells show no further sign of the disease, according to a case report published Thursday in The New England Journal of Medicine.

Since therapy was applied, he hasnt had any pain, any complications. He is free of any transfusions. He plays sports and goes to school, said Dr. Philippe Leboulch, an author of the new research and a professor of medicine at the University of Paris. So we are quite pleased with the results.

This success provides proof of concept for human patients, Leboulch said.

According to Dr. Marina Cavazzana, senior author of the study and head of the biotherapy department at Necker, all the biological tests we perform lead us to think he is cured. Yet, she added, the answer to the question of whether he is truly cured can be provided only by the longer follow-up.

Still, hopes are running high that patients with this very devastating disease can receive this therapy in the next five years, Cavazzana said. This is our hope, and we work very hard to attain it.

A global burden

Worldwide, more than 275,000 infants are born with sickle cell disease each year. In the United States, approximately 100,000 people, most of African ancestry or identifying as black, currently have it. About one in every 365 black children in the US is born with sickle cell disease, for which the life expectancy is now about 40 to 60 years.

Sickle cell disease is one of the most common gene disorders in the world, explained Leboulch. A genetic mutation causes hemoglobin, the main constituent of red blood cells, to distort the shape of the cell, and this causes the blood to aggregate or clog.

This leads to tremendous pain, anemia and also lesions of organs that ultimately result in shortness of life expectancy, Leboulch said. So what we did here was, we tried to inhibit the process of aggregation.

Essentially, researchers extracted bone marrow from the patient, harvested the stem cells and altered the genetic instructions so that they would make normal hemoglobin. Next, they treated the patient with chemotherapy for four days to eliminate his diseased stem cells. Finally, they returned the treated stem cells via an IV into his bloodstream.

At that point, the new cells that were modified outside the body started to make new blood cells, and we hope this will be stable for the life of the patient, Leboulch said.

Before receiving treatment, the teen had terrible pain and needed blood transfusions, which required twice-yearly hospitalizations, Leboulch explained. His many complications included necrosis of the hip, which necessitated hip replacement surgery.

Hope for all patients

Going forward, the plan is to proceed through clinical trials and, if results are promising, make the treatment available to patients. Leboulch and his colleagues are using the same genetic therapy to treat a similar disease called thalassemia, another inherited blood disorder in which patients have less hemoglobin and fewer red blood cells than normal. Severe forms require regular blood transfusions.

Leboulch and his colleagues have global phase 2 and phase 3 trials for the thalassemia treatment underway in France, the US, Australia and Thailand.

For sickle cell disease, a companion trial in the US is underway. I understand that seven (sickle cell) patients have been treated already. Of course, the outcome is much shorter, and we dont have the results just yet, but its coming along, Leboulch said.

To apply this to a baby or a very young child should be at least as effective or more, he said. Doing it with older patients, who have had years of complications, could be more challenging.

Leboulch also noted that gene therapy is easier on patients than procedures requiring outside donors. Previously, hematopoietic stem cell transplant, which replaces a patients bone marrow with that of a donor, has proved an effective cure for some patients.

According to Dr. Alexis Thompson, president-elect of the American Society of Hematology, the majority of sickle cell disease patients do not have a sibling who would be an appropriate match for bone marrow donation.

Gene therapy holds promise because a patient serves as his own donor, and the risks are much reduced since theres no possibility of a mismatch, said Thompson, who was not involved in this research but is an investigator on a related gene therapy study.

I think this is a really very exciting advancement, she said, adding that if the results seen in France can be duplicated, this would provide for a new direction for patients who need a curative option.

According to Dr. Trish Wong of Oregon Health and Science University, the new study is truly amazing work proof of principle that a cure for this chronic, devastating disease is in sight. Wong was not involved in the new research.

Gene therapy offers hope for all patients with sickle cell disease, regardless of whether they have a bone marrow match or not, Wong wrote in an email.

Time is still needed to assess the success of this treatment and the possibility of later side effects, said Wong. But any patient with severe sickle cell disease will tell you that being able to live a life for even a year without medications or fear of pain or hospitalization is substantial.

Finally, Dr. Grace Onimoe of the American Sickle Cell Anemia Association noted that the life expectancy of a patients with sickle cell disease remains decades lower than that of the general population while children throughout the world continue to suffer. Onimoe, who was not involved in the new research, said, As more work continues in the area of gene therapy to enhance safety and reduce potential complications, we remain optimistic of the promise it holds.

Leboulch also feels very hopeful.

Now, we want to be cautious, of course, and we dont want to say that this is the cure for tomorrow or the next day for everybody, he said. At the same time, what weve observed is really convincing, and we just hope that we can move this along to make it available to patients.

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Sickle cell anemia patient 'cured' by gene therapy, doctors say - FOX31 Denver