Dive Brief:

The EMA's green light for Bluebird's manufacturing removes a final hurdle standing in the way of marketing the gene therapy, which costs $1.8 million per patient.

A requirement from European authorities to narrow drug product specifications for Zynteglo forced the company to delay the gene therapy's launch later than when Wall Street analysts had expected.

In a statement, Apceth said it's ready for the challenge to bring Bluebird's treatment to market. Between 2,000 and 3,000 patients in the European Union would be eligible under the conditions approved by regulators for Zynteglo's use.

Bluebird has cautioned investors to take a long view of the new treatment's prospects, and to expect a slow start. In addition to winning approval for the new manufacturing specifications, Bluebird has to navigate through healthcare systems that aren't used to paying large sums for a one-time treatment.

In hopes to alleviating those problems, the company has offered an installment plan that would require later payments only if the treatment continues to benefit patients. The hope is that Zynteglo saves healthcare dollars by sparing beta-thalassemia patients the need for regular blood transfusions and the complications that can go along with them.

Patients with the blood disorder carry a genetic mutation that hinders the body from effectively producing the crucial oxygen-carrying protein hemoglobin. As a result, they often require transfusions every two to five weeks to fight anemia.

"This is one step along the commercial journey as we advance our ongoing launch and market access activities on a country-by-country basis," said Alison Finger, Bluebird's chief commercial officer, in the company's statement on the EMA's nod.

In a September company presentation, Bluebird said it wants to make sure to "get the model right" as it looks toward future gene therapies it's developing in its pipeline. The company is initially planning to offer Zynteglo through treatment centers in Germany, Italy, the U.K. and France, with a drug manufacturing facility in Munich.

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Bluebird gets European green light for gene therapy production - BioPharma Dive

Zolgensma, a lifesaving treatment for infants and the worlds most expensive drug, has been used to treat 100 patients since its launch and brought in $160 million for its maker Novartis (NVS) last quarter, beating analysts expectations.

The gene therapy is a treatment for spinal muscular atrophy, a rare and devastating neurological disease. It carries a record price tag of $2.1 million, or an annualized cost of $425,000 per year for five years.

Novartis said Tuesday that roughly 99% of SMA patients who qualified for Zolgensma got coverage of the one-time therapy, although some had to go through an approval process to receive the drug. The company also indicated that it made progress in striking deals with health plans to cover the drug, saying that agreements are in place covering roughly 90% of patients insured commercially and roughly 30% of patients covered by Medicaid.

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I think the overall uptake that were seeing very early in the launch speaks to the promise of the product, the physician excitement, and the parent and patient desire to get kids on gene therapy, said Dave Lennon, president of AveXis, Novartiss gene therapy business.

The strong sales numbers came over a summer that saw a controversy involving manipulation of data used to support Zolgensmas approval by the Food and Drug Administration. In an unusual rebuke, the agency said in August that AveXis knew that preclinical data had been falsified before the drug was approved in May, but did not inform the Food and Drug Administration until later. The agency said that the drug should stay on the market, but the scandal sparked anger from lawmakers and a pledge from Novartiss CEO, Vas Narasimhan, to move more quickly on disclosing issues around data integrity.

Lennon said Novartis worked quickly to reassure patients and physicians of Zolgensmas quality, and the data manipulation scandal had no real impact on the treatments commercial performance, Lennon said.

Zolgensmas early success could be a worrying sign for Biogen, whose Spinraza has been the treatment of choice for SMA since its approval in 2016. More than 50% of patients treated with Zolgensma had switched over from Spinraza, according to Novartis, preferring a one-time therapy over Biogens every-four-months treatment.

Zolgensmas sales outstripped what analysts had forecasted. One average of analysts projections, from Bloomberg, had pegged the drugs sales for the quarter at $86 million. Another compiler of financial estimates, FOA, had gauged analysts consensus at $106 million.

Novartis expects revenue to grow. The company is counting on approvals for Zolgensma in Europe and Japan next year, and it recently presented data demonstrating the gene therapys effects on older SMA patients. Novartis is also counting on an expansion of newborn testing for SMA, which is currently done in 30% of U.S. states but could rise to 70% by 2020, according to the company.

Time is neurons for these kids, and we really want to make sure they get gene therapy as soon as possible, Lennon said.

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Novartis gene therapy brings in $160 million, beating expectations - STAT

Cobra Moradian, Fatemeh Rahbarizadeh

Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Correspondence: Fatemeh RahbarizadehDepartment of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Jalal AleAhmad Highway, Tehran 14115-111, IranTel +98 21 82883884Fax +98 21 82884555Email rahbarif@modares.ac.ir

Background: Breast cancer stem cells (BCSCs) are cells with a higher ability to metastasis and resistance to conventional treatments. They have a phenotype of (CD44high/CD24low) and the unlimited ability for proliferation. Development of strategies to target the BCSC population may lead to the establishment of more effective cancer therapies. Pseudomonas exotoxin A (PE) is a potent cytotoxic protein. CXCR1 promoter provides BCSC and HER2 specificity on transcription level. 5UTR of the basic fibroblast growth factor-2 (bFGF 5UTR) provides tumor specificity on translation level. Here, we utilized a mutant form of PE encoding DNA PE38, CXCR1 promoter and bFGF 5UTR to target BCSCs.Methods: The stemness of SK-BR-3, MDA-MB-231 and MCF10A cell lines were evaluated based on the expression of the CD44high/CD24low stem cell signature and the ability to form mammospheres. Then, the cell lines were transfected with constructs encoding luciferase/PE38 under the control of the CMV/CXCR1 promoter with or without bFGF 5UTR. Luciferase protein expression was evaluated using dual-luciferase reporter assay. PE38 transcript expression was measured by real-time PCR, and the cytotoxic effect of PE38 protein expression was determined by MTT assay.Results: The percentage of CD44high/CD24low population did not correlate to mammosphere forming efficiency (MFE). Given that the percentage of CD44 high/CD24 low is not a conclusive BCSC profile, we based our work on the mammosphere assay. However, in comparison with MCF10A, the two tumorigenic cell lines had higher MFE, probably due to their higher BCSC content. Reporter assay and real-time PCR results demonstrated that CXCR1 promoter combined with bFGF 5UTR increased BCSC-specific gene expression. Meanwhile, tightly regulated expression of PE38 using these two gene regulatory elements resulted in high levels of cell death in the two tumorigenic cell lines while having little toxicity toward normal MCF10A.Conclusion: Our data show that PE38, CXCR1 promoter and bFGF 5UTR in combination can be considered as a promising tool for killer gene therapy of breast cancer.

Keywords: breast cancer stem cell, PE38, CXCR1 promoter, bFGF-2, HER2, mammosphere

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Targeted Toxin Gene Therapy Of Breast Cancer Stem Cells Using CXCR1 Pr | OTT - Dove Medical Press

Some gene therapies, such as bluebird bios Zynteglo, work by modifying a patients own blood stem cells to deliver a functioning gene. While they hold great potential as life-saving treatments for many immune system disorders and blood-based conditions, the process for administration can be costly and time-consuming.

In a study published in the journal Blood, scientists at Scripps Researchdescribed a possible way to more efficiently deliver genes to improve gene therapy treatment outcomesand it involves a close relative to a natural compound found in grapes.

Take Zynteglo, formerly known as LentiGlobin. Approved in the EU to treat beta thalassemia, an inherited blood disorder, it uses a lentiviral vector to insert a functioning version of the beta-globin gene into a patients blood-producing hematopoietic stem cells (HSCs) outside of the body. When the cells are given back to the patient, the gene can multiply and start to make healthy red blood cells.

Industry Insight Survey: Direct-to-Patient Distribution of Clinical Supplies

This industry survey seeks to gain insight on trial sponsors' perspective on offering a DTP option and their current level of awareness and understanding of any factors that may influence their ability to do so. The first 50 qualified respondents will receive a $5 Amazon gift card.

However, HSCs protect themselves with structures known as interferon-induced transmembrane (IFITM) proteins against viral attacks. Therefore, in preparation for a gene therapy, the lentiviral vectors could be intercepted several timeswasting a large amount of expensive materialsbefore a successful delivery.

This is why gene therapy of hemopoietic stem cells has been hit-or-miss, Bruce Torbett, the studys senior author, said in a statement. We saw a way to potentially make the treatment process significantly more efficient.

Torbett and colleagues at Scripps Research focused on caraphenol A, a small molecule related to resveratrol, which is a natural compound produced by grapes widely known for its antioxidant and anti-inflammatory effects.

The team found that adding caraphenol A to human HSCs, along with lentiviral vectors, could reduce the cells natural defenses by lowering the levels of IFITM2 and IFITM3, allowing the vectors to pass more easily. The effect was even more pronounced once the HSCs were transplanted into mice, as the cells divided and produced blood cells with the corrected gene, according to the team.

RELATED:Improving viral vectors for hemophilia gene therapies by tricking the immune system

Because gene therapy holds the promise of a potential cure for debilitating diseases that are deadly or require long-term care, scientists have been exploring new ways to improve it. A research team at the San Raffaele Telethon Institute for Gene Therapy in Italy recently found integrating the protein CD47 in the surface of lentiviral vectors could help them escape detection and destruction by the immune system once inside the body.

Torbett and his team believe caraphenol A could reduce costs of HSC-based gene therapy, which are high: Bluebird has priced Zynteglo at 1.6 million ($1.8 million) in Europe. It could also save time by helping patients get the therapy sooner. And because the longer stem cells stay outside of the body, the more likely they are to lose their ability to self-generate, more efficient gene delivery could also preserve their self-renewing properties, Tobett said.

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Could a grape-based compound improve gene therapy efficiency? - FierceBiotech

During the third-quarter financial call, Vasant Narasimhan, CEO of Novartis, noted that questions from European and Japanese regulators regarding chemistry, manufacturing and controls (CMC) were behind expected decision dates on Zolgensma (onasemnogene abeparvovec) being pushed back into 2020.

At present, the company expects to receive opinions from the European Medicines Agency (EMA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) in the first quarter and the first half of 2020, respectively.

Narasimhan revealed few other details regarding the questions, only that there were an extensive set of questions with respect to manufacturing, to which it had submitted responses. Reuters stated that he also confirmed that the decision delay was not due to the revelation of data manipulation in August.

Despite the setback on potential approval date, the company was able to confirm that the product had achieved US sales of $160m (143m), arriving higher than analyst predictions of $98m (88m).

When questioned on the patient numbers this related to, on paid programs, Narasimhan confirmed that approximately 100 patients had been treated though other patients had received the gene therapy through treatment in clinical trials.

Once approved in elsewhere in the world, Narasimhan predicted such number could increase rapidly: I think in some countries in Europe, as well in the Middle East, there could be very strong demand coming very quickly after approval.

He cited pent-up demand as a reason that sales would increase quickly, and also pointed to early access programs being made available in France, Portugal and Germany as another positive long-term sign for the product.

The company will need to see substantial return on the product, after investing $8.7bn in the AveXis acquisition to gain access to the technology.

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Novartis gene therapy held up by manufacturing questions - BioPharma-Reporter.com

Sanofi is playing catch-up in gene therapy, but new CEO Paul Hudson is taking quick steps to close the gap. A reorganization of the R&D unit is intended to pivot thedrugmaker toward immuno-oncology drugs and gene therapies. And to hasten the transition, the company is retrofitting a vaccine plant in France into a gene therapy manufacturing operation.

A spokesman Monday confirmed Sanofi is preparing teams at its Lyon-Gerland site to work on vector-based gene therapies. John Reed, Sanofi's head of R&D,spoke about the project in an interview with BioPharma Dive.The drugmaker expects the facility to be operational a year from now.

RELATED: Sanofi quits Voyager gene therapy deal once worth up to $845M

De-Risking the Solid Form Landscape of an API

This presentation will discuss how predictable stability and solubility can minimize development timelines and cost. Attend to hear about two case studies exemplifying the importance of understanding the hydration space of an API and how hydrate formation may be avoided by development of a robust crystallization procedure.

Sanofi has invested about 25 million in the Lyon-Gerland site over the last five years. In 2013, the drugmaker struck a deal with France's Transgene to share the cost of a 10 million facility thereto manufacture Transgene's immuno-oncology therapies.

The Lyon vaccine facility is being retrofitted even as Sanofi this summer reworked itsgene therapy partnership with Voyager Therapeutics. Sanofi dumped two programs it has started with Voyager, and now the two will develop adeno-associated virus capsids the protein shells of the virusfor the delivery of gene therapies. Sanofi gets the exclusive option to use these capsids to deliver treatments for up to two non-CNS diseases.

RELATED: Sanofi U.S. plant sets new bar for biologics production

The project also comes as Sanofi has been upgrading other parts of its manufacturing network for the future. Last week, it opened a new biologics plant in Massachusetts that it considers its prototype plant of the future. In the digitally enabled manufacturing facility, all manufacturing stages are controlled through analytical processes that are forecast to avoid variations.

Plant operators also have access to data analytics or augmented reality solutions that can help them make real-time decisions and adjustments. Sanofisaid the remade plant is 80 times more productive while also reducing energy use and emissions by 80%.

As for gene therapy production, Sanofi is following other companies such bluebird bio and Gileads Kite Pharma in building viral vector manufacturingfacilities to serve their gene therapy or CAR-T development programs, which are much further along than Sanofi's.

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Sanofi starts on viral vector facility as its R&D focus shifts to gene therapies - FiercePharma

The Centre for Process Innovation (CPI) has announced it has overcome a significant bottleneck in the development of gene therapies.

CPI said its CRD IUK project, which was launched in partnership with Cobra Biologics and GE Healthcare Life Sciences, has been successful in its aim to develop a scalable, cost-effective purification process for adeno-associated viruses (AAVs).

AAVs are a vital technology for the delivery of gene therapies into patients. By transporting genetic material into patient cells, AAVs are able to provide a cure for otherwise untreatable diseases.

However, manufacturers are currently hindered by the low efficiency of AAVs production, which slows down the overall development timescale of gene therapies, ultimately increasing the cost for payers in healthcare systems.

The CRD IUK project was funded by a 570K grant from Innovate UK and focused on optimising an AAV purification process using GE Healthcare Life Sciences Fibro chromatography material. The material is based on electrospun cellulose nanofibers that contain different chromatography functionalities, overcoming the limitations of existing chromatographic supports.

Whilst the technology was understood to be highly effective for purification of biomolecules, the CRD IUK project extended the technologys effectiveness to AAVs. After assessing the technology, a multistep purification process was developed for AAV purification.

Daniel Smith, chief scientific officer, Cobra Biologics, said:We are delighted to have been part of this collaboration working to develop robust processes for use in the development of gene therapies. This project has provided a scalable, cost-effective fibre-based chromatography method for production of AAVs that will greatly enhance development of innovative new treatments.

John Liddell, chief technologist, CPI, said: Gene therapies have the potential to be transformative for disease areas with unmet clinical need, and effective manufacturing processes are crucial for reaching the time and cost points necessary for achieving commercialisation. This was the second Innovate UK-funded project related to viral vectors for CPI and therefore further enhances the Catapult centres ability to support growth of this emerging sector, which has been confirmed in subsequent gene therapy projects.

Oliver Hardick, business leader, Puridify, GE Healthcare Life Sciences, added: This has been an excellent collaboration with Cobra Biologics and CPI. Together, we have made a big step forward in the production of viral vectors to be used in gene therapies. The success of the project will significantly reduce the cost and time associated with development and manufacturing of AAVs, helping to accelerate delivery of gene therapy products to market.

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Industry collaboration overcomes significant bottleneck for gene therapy production - EPM Magazine

SOUTH PLAINFIELD, N.J., Oct. 24, 2019 /PRNewswire/ --PTC Therapeutics, Inc., (NASDAQ: PTCT) today announced new results from its investigational gene therapy, PTC-AADC, in patients living with aromatic L-amino acid decarboxylase (AADC) deficiency. The datademonstrated clinically meaningful and sustained improvements in motor, cognitive and language milestones. These included the ability to sit, walk, and talk and represents up to five years of follow up post-treatment.1,2 PTC-AADC is a one-time gene therapy treatment of the human dopa decarboxylase (DDC) gene administered into the putamen, which supports production of key neurotransmitters. The data were presented at the Child Neurology Society 48th Annual Meeting.

"We are excited to see the transformational effects in AADC deficiency patients in this long-term study as patients with severe AADC deficiency never achieve the ability to sit, walk or talk," said Stuart Peltz, Ph.D., Chief Executive Officer of PTC Therapeutics. "We are on track to submit a BLA to the FDA by the end of the year and are proud to be on the verge of bringing the first commercial treatment for AADC deficiency patients which is in line with our mission of bringing clinically differentiated treatments to patients with rare disorders."

New analysis evaluated outcomes of 26 patients with AADC deficiency across three separate clinical trials,2 making it the most comprehensive analysis of patients treated with PTC-AADC to date. Specifically, these results showed that 12 months post-treatment with PTC-AADC, patients' mean body weight had increased from 12.0 kg to 15.2 kg, and the frequency of oculogyric crises (involuntary upward eye movement) was reduced.2 Dyskinesia (involuntary movements) was the most frequently recorded adverse event, however most events were mild or moderate and all cases resolved by 10 months post-treatment.2

"In addition to failing to reach key developmental milestones, such as walking and talking, children with AADC deficiency can experience severe symptoms that affect their everyday lives. These symptoms can include episodes of oculogyric crises, which can last for minutes or hours and involve sustained upward movement of the eyes, involuntary movements of the neck, tongue protrusions and jaw spasms, which can be very distressing for patients and their families," said Claudio Santos, M.D., Senior Vice President, Global Medical Affairs, PTC Therapeutics. "The post-treatment data presented at CNS confirm reductions in the number of patients experiencing oculogyric crises, suggesting that this gene therapy treatment has the potential to make a real difference in the lives of patients with AADC deficiency."

A separate analysis of a long-term study demonstrated the sustained efficacy of PTC-AADC up to five years.1 These are the longest data available for any investigational treatment for AADC deficiency. These results showed clinically meaningful and sustained improvements in motor, cognitive and language milestones up to five years post-treatment with PTC-AADC.1

An additional abstract building on the existing understanding of AADC deficiency was also presented, giving a disease state overview that highlights the potential importance of a gene therapy to treat this condition.3

About aromatic L-amino acid decarboxylase (AADC) deficiencyAromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic condition caused by a mutation in the dopa decarboxylase (DDC) gene, resulting in a lack of functioning AADC enzyme, which is responsible for the final step in the synthesis of key neurotransmitters dopamine and serotonin.4

AADC deficiency results in delays or failure to reach developmental milestones such as head control, sitting, standing, walking, or talking, low muscle tone (also known as muscular hypotonia), severe, seizure-like episodes involving involuntary eye movement (also known as oculogyric crises), autonomic abnormalities, and the need for life-long care.4 Given this neurologically devastating illness, patients with severe AADC deficiency have a high risk of death during childhood. There are currently no approved therapies that address the underlying cause.

About PTC Therapeutics, Inc.PTC is a science-driven, global biopharmaceutical company focused on the discovery, development and commercialization of clinically-differentiated medicines that provide benefits to patients with rare disorders. PTC's ability to globally commercialize products is the foundation that drives investment in a robust pipeline of transformative medicines and our mission to provide access to best-in-class treatments for patients who have an unmet medical need. To learn more about PTC, please visit us onwww.ptcbio.comand follow us onFacebook, on Twitter at @PTCBio, and on LinkedIn.

For More Information:

Investors:Emily Hill+ 1 (908) 912-9327ehill@ptcbio.com

Media: Jane Baj+1 (908) 912-9167jbaj@ptcbio.com

References:

Forward-LookingStatements:This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this release, other than statements of historic fact, are forward-looking statements, including statements regarding: the future expectations, plans and prospects for PTC; expectations with respect to PTC's gene therapy platform, including any potential regulatory submissions; PTC's strategy, future operations, future financial position, future revenues, projected costs; and the objectives of management. Other forward-looking statements may be identified by the words "guidance", "plan," "anticipate," "believe," "estimate," "expect," "intend," "may," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions.

PTC's actual results, performance or achievements could differ materially from those expressed or implied by forward-looking statements it makes as a result of a variety of risks and uncertainties, including those related to: expectations with respect to the potential financial impact or PTC's ability to realize the anticipated benefits of the acquisition of Agilis and its gene therapy platform, including with respect to the business of Agilis and expectations with respect to the potential achievement of development, regulatory and sales milestones and contingent payments to the former Agilis equityholders with respect thereto and PTC's ability to obtain marketing approval of PTC-AADC and other product candidates acquired from Agilis, will not be realized or will not be realized within the expected time period; significant transaction costs, unknown liabilities, the risk of litigation and/or regulatory actions related to the acquisition of its gene therapy pipeline, as well as other business effects, including the effects of industry, market, economic, political or regulatory conditions; the eligible patient base and commercial potential of PTC-AADC; and the factors discussed in the "Risk Factors" section of PTC's most recent Annual Report on Form 10-K, as well as any updates to these risk factors filed from time to time in PTC's other filings with the SEC. You are urged to carefully consider all such factors.

As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. There are no guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially successful, including PTC-AADC.

The forward-looking statements contained herein represent PTC's views only as of the date of this press release and PTC does not undertake or plan to update or revise any such forward-looking statements to reflect actual results or changes in plans, prospects, assumptions, estimates or projections, or other circumstances occurring after the date of this press release except as required by law.

View original content:http://www.prnewswire.com/news-releases/ptc-therapeutics-announces-results-from-long-term-aadc-deficiency-gene-therapy-treatment-demonstrating-sustained-improvements-300944629.html

SOURCE PTC Therapeutics, Inc.

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PTC Therapeutics Announces Results from Long-Term AADC Deficiency Gene Therapy Treatment Demonstrating Sustained Improvements - BioSpace

October 22 2019, 12:01am,The Times

Progress in gene editing has huge potential and should be welcomed

A leap forward in genetic science has the potential to improve the life of our species. It builds on the momentous 2012 discovery of the Crispr/Cas9 technique, which made it vastly easier to edit genes. This breakthrough revolutionised the study of heritable human diseases by allowing scientists to reproduce them more easily in laboratory animals, and opened up the tantalising possibility of one day curing them by editing embryos or even the genes of adult patients. The new advance, by scientists at Harvard and MITs Broad Institute, makes the technique far more effective, meaning that its use in treating diseases is becoming a real prospect. We should embrace it.

The new technique tackles a key weakness in Crispr/Cas9 gene editing. In 2012 scientists realised that

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The Times view on a breakthrough in treating heritable disease: Gene Therapy - The Times

A more efficient approach to gene therapy that could lower costs and improve patient outcomes has recently been developed by a team from Scripps Research. This work, published on October 17 in the journal Blood, offers a potential alternative to the standard process of delivering gene therapy, which is expensive, time-consuming, and requires many steps to administer healthy genes to the patients stem cells.

If you can repair blood stem cells with a single gene delivery treatment, rather than multiple treatments over the course of many days, you can reduce the clinical time and expense, which removes some of the limitations of this type of approach, explained research leader Bruce Torbett, PhD, associate professor in the Department of Immunology and Microbiology.

The goal of gene therapy is to introduce a healthy version of a gene to a patients stem cells to replace a defective copy of this gene. This approach is designed to treat inherited conditions caused by genetic mutations, such as sickle cell anemia. Patients with sickle cell have a mutation in a gene that codes for a protein in blood cells, leading to misshaped cells that cause a myriad of clinical issues. The goal of gene therapy is to replace this mutated gene with a healthy copy to restore normal protein synthesis and eliminate the disease symptoms. This is often done by implanting the healthy gene into a modified virus, known as a viral vector, and having this virus use its innate ability to infiltrate host cells and inject this healthy gene into them.

Gene therapy treatments typically require the harvesting of a small population of hemopoietic stem cells, the cells that serve as precursors for all types of blood cells, from the patients blood. Viral vectors containing therapeutic genes are then introduced to these cells with the goal being for them to insert this genetic information into the stem cells.

The hemopoietic stem cells defend themselves from viral penetrance using interferon-induced transmembrane (IFITM) proteins that block the viral vectors. For this reason, many gene therapies require a large number of vectors and many attempts for success, which is an expensive process.

In their work, the Scripps team focused on caraphenol A, a molecular relative of resveratrol, a natural compound made by grapes and other plants present in wine. Resveratrol is known to have antioxidant and anti-inflammatory properties. Although caraphenol A shares these anti-inflammatory properties, it served a much different purpose in this work.

Observing the chemical properties of resveratrol and associated molecules such as caraphenol A, Torbett and colleagues wanted to investigate whether they could be used in gene therapy to improve the viral vectors ability to enter blood stem cells. Enhancing viral vector penetrance into host cells would be advantageous, being that the cells natural defense mechanisms against viral attacks present a challenge in gene therapy.

This is why gene therapy of hemopoietic stem cells has been hit-or-miss, explained Torbett. We saw a way to potentially make the treatment process significantly more efficient.

The researchers found that by adding caraphenol A to human hemopoietic stem cells with the viral vector present, the stem cells defense was weakened, and the viral penetrance increased. When these treated stem cells were implanted into mice in this study, they were observed to produce blood cells that contained the new genetic information.

In addition to saving costs, this approach also cuts down the time required for a patient to receive a gene therapy treatment. Reducing treatment time is not only convenient for the patient, but it lowers the chance that the stem cells lose their self-renewing properties as well. The more time the stem cells spend being outside of the body and being manipulated, the higher the likelihood of them losing their proliferative ability is.

Torbetts team is continuing to research how stem cells combat viral attacks, hoping to lower the cost of gene therapy while improving efficiency.

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New Gene Therapy Approach Reduces Cost and Improves Efficiency - DocWire News