Category Archives: Genetic Therapy

Early data trends from first patient dosed in the AVR-RD-04 investigational gene therapy program for cystinosis show improvements across multiple measures

Data from the Phase 1 and Phase 2 trials of AVR-RD-01 support potential long-term engraftment and durable, endogenous production of functional enzyme in patients with Fabry disease

First Phase 2 Fabry patient treated using plato gene therapy platform shows plasma enzyme activity at one month 4.0 times higher than mean activity of other Phase 2 patients treated using academic platform at same timepoint

Analyst and investor event will be webcast today, Feb. 10, 2020, at 7:00 p.m. ET, in conjunction with WORLDSymposiumTM

AVROBIO, Inc. (NASDAQ: AVRO), a leading clinical-stage gene therapy company with a mission to free people from a lifetime of genetic disease, today announced new initial data from the first patient dosed in the investigational gene therapy program for cystinosis, showing improvements in early measures at three months compared to baseline. The company also unveiled new clinical data showcasing a sustained biomarker response in patients for up to 32 months after receiving the companys investigational gene therapy for Fabry disease across metrics including vector copy number (VCN), substrate levels and enzyme activity. Additionally, the company reported on the clinical debut of its platoTM gene therapy platform. These data showed improved enzyme activity, transduction efficiency and VCN in drug product manufactured using plato compared with drug product produced using the academic platform, as well as higher in vivo enzyme activity at one month in the first patient treated with plato, as compared to other patients treated using the academic platform. All these data will be presented today, during the 16th Annual WORLDSymposiumTM in Orlando, Fla.

"We have now dosed 10 patients across three trials for two lysosomal disorders and were delighted with the data were seeing. We have followed six patients in our Fabry trial for more than a year and one for nearly three years, and they are consistently producing the functional enzyme that was missing as a consequence of their genetic disease, suggesting a potentially durable effect from a single dose," said Geoff MacKay, AVROBIOs president and CEO. "Furthermore, we believe that early data from the first clinical application of plato support our decision to invest heavily from AVROBIO's earliest days in this state-of-the-art gene therapy platform. We believe these data collectively indicate that were making exciting progress toward our goal of freeing patients and families from the life-limiting symptoms and relentless progression of lysosomal disorders."

Three-month data from first patient in investigational AVR-RD-04 trial in cystinosisAVROBIO reported initial data from the first patient dosed in the investigator-sponsored Phase 1/2 trial of the companys AVR-RD-04 investigational gene therapy for cystinosis, a progressive disease marked by the accumulation of cystine crystals in cellular organelles known as lysosomes. Patients with cystinosis accumulate the amino acid cystine, which can lead to crystal formation in the lysosomes of cells, causing debilitating symptoms including corneal damage, difficulty breathing and kidney failure, often leading to a shortened lifespan. The current standard of care for cystinosis, a burdensome treatment regimen that can amount to dozens of pills a day, may not prevent overall progression of the disease.

As of the safety data cut-off date of Jan. 27, 2020, which was approximately three months following administration of the investigational gene therapy to the first patient in the AVR-RD-04 program, there have been no reports of safety events attributed to the investigational drug product. In addition, no serious adverse events (SAEs) have been reported as of the safety data cut-off date. Adverse events did not suggest any unexpected safety signals or trends.

Three months following administration of AVR-RD-04, the first patient had a VCN of 2.0. VCN measures the average number of copies of the lentiviral-vector inserted transgene integrated into the genome of a cell and can be used to help assess the durability of a gene therapy. Initial data on another biomarker show that the patients average granulocyte cystine level -- one of the trials primary endpoints -- decreased from 7.8 nmol half cystine/mg protein two weeks after cysteamine discontinuation, to 1.5 at three months post-gene therapy.

The ongoing open-label, single-arm Phase 1/2 clinical trial evaluating the safety and efficacy of AVR-RD-04 is sponsored by AVROBIOs academic collaborators at the University of California San Diego (UCSD), led by Stephanie Cherqui, Ph.D. The trial is actively enrolling up to six participants at UCSD.

Interim data continue to support potential first line use of AVR-RD-01 in Fabry diseaseFour patients have been dosed in the Phase 2 trial (FAB-201), and five patients in the Phase 1 investigator-led trial of AVR-RD-01 in Fabry disease.

VCN data continue to be stable at 32 months following AVR-RD-01 treatment for the first patient in the Phase 1 trial, suggesting successful engraftment, which is critical to the long-term success of investigational ex vivo lentiviral gene therapies. The VCN data trend was generally consistent across the seven other Phase 1 and Phase 2 trial participants out six to 24 months.

The first three AVR-RD-01 Phase 2 patients entered the study with minimal endogenous enzyme activity. At nine, 12 and 18 months after dosing, data from these three patients indicate sustained increased leukocyte and plasma enzyme activity, suggesting that they are now producing an endogenous supply of functional alpha-galactosidase (AGA) enzyme. This enzyme is essential for breaking down globotriaosylceramide (Gb3) in cells; without it, a toxic metabolite, lyso-Gb3, may accumulate, potentially causing cardiac and kidney damage and other symptoms.

For two Phase 2 patients, data indicate that their decreased plasma lyso-Gb3 levels, a key biomarker for monitoring Fabry disease, have been sustained below their baseline at six and 18 months after dosing. The third Phase 2 patient, a cardiac variant who does not have classic Fabry disease, did not show a decrease in plasma lyso-Gb3 levels, as expected. Cardiac and kidney function measures in the Phase 2 trial remained within normal range for patients who had available 12-month data.

As previously reported, a kidney biopsy taken at 12 months post-treatment for the first patient in the Phase 2 trial showed an 87-percent reduction in Gb3 inclusions per peritubular capillary. The company believes this data point, the primary efficacy endpoint for the Phase 2 trial, supports the potential of AVR-RD-01 to reduce Gb3 levels in tissue, including in the kidney.

In the Phase 1 trial of AVR-RD-01, four of the five patients had their plasma lyso-Gb3 levels reduced between 26 and 47 percent compared to their pre-treatment baseline levels. Data from the other patient in the trial, who remains off enzyme replacement therapy (ERT), through month six showed an initial decline and at month 12 showed a 23-percent increase in lyso-Gb3 levels, as compared to pre-treatment levels. This patients lyso-Gb3 levels remain within the range for the Fabry disease patients on ERT observed in this study.

Overall, three of the five Phase 1 patients have discontinued ERT and all three remain off ERT for six, 14 and 15 months.

As of the safety data cut-off date of Nov. 26, 2019, there have been no safety events attributed to AVR-RD-01 drug product in either the Phase 1 or Phase 2 trial. Through the safety data cut-off date, four SAEs have been reported in the FAB-201 trial and two SAEs in the Phase 1 trial. The fourth Phase 2 patient, who was dosed after the safety data cut-off date, has reported an SAE, which was not attributed to AVR-RD-01 and which subsequently resolved. Across both studies, each of the SAEs has been consistent with the conditioning regimen, stem cell mobilization, underlying disease or pre-existing conditions. Pre-existing low anti-AGA antibody titers have been detected in four patients in the Phase 1 trial and a transient low titer was observed but not detectable in subsequent measures in one patient in the Phase 2 trial.

The Phase 1 trial is fully enrolled. AVROBIO continues to actively enroll the Phase 2 trial in Australia, Canada and the U.S. The FAB-201 trial is an ongoing open-label, single-arm Phase 2 clinical trial evaluating the efficacy and safety of AVR-RD-01 in eight to 12 treatment-nave patients with Fabry disease.

Successful clinical debut of platoTM gene therapy platformAVROBIO also shared preliminary results from the first two patients to receive busulfan conditioning. Conditioning is an essential step in ex vivo lentiviral gene therapy designed to clear space in the bone marrow for the cells carrying the therapeutic transgene to engraft. The conditioning regimen developed as part of AVROBIOs plato platform includes therapeutic dose monitoring to assess how rapidly the individual patient metabolizes busulfan so physicians can adjust the dose as needed, with a goal of minimizing side effects while maximizing the potential of durable engraftment.

AVROBIO is implementing its precision dosing conditioning regimen across its company-sponsored clinical trials as part of the plato platform. The fourth patient in AVROBIOs Phase 2 Fabry trial received a precision dosing conditioning regimen with busulfan as part of the plato platform, while the first patient in the investigator-led cystinosis trial received busulfan but not as part of the plato platform.

These two patients both had rapid neutrophil and platelet count recovery, with a trajectory that was similar to the patients who enrolled earlier in the Fabry trials and who received a melphalan conditioning regimen. Side effects, which included nausea, mucositis, fever, rash and hair loss, developed eight to 10 days after dosing with busulfan and then resolved quickly.

The company also reported preliminary data from the first drug product produced using the plato gene therapy platform, which was used to dose the fourth patient in the Phase 2 Fabry trial (FAB-201). Early data indicate that enzyme activity and transduction efficiency for the drug product used to dose the fourth patient were 2.2 times higher than the mean of the drug product used to dose the first three patients in FAB-201. VCN for the drug product used to dose the fourth patient was 1.8 times higher than the mean of the drug product for the first three patients dosed in FAB-201. The drug product for the first three patients in FAB-201 was manufactured using a manual process first developed by AVROBIOs academic collaborators. The automated manufacturing embedded in plato leverages optimized processes developed at AVROBIO.

At one month following administration of the plato-produced investigational gene therapy for the fourth patient in the Phase 2 Fabry trial, initial data show the patients plasma enzyme activity level to be 4.0 times higher than the mean activity level of the first three patients in the Phase 2 Fabry trial at the same timepoint.

The investigational drug product used to dose the first patient in the AVR-RD-04 program for cystinosis, which included a four-plasmid vector but not platos automated manufacturing process, also showed increased performance in line with the increased performance recorded for the drug product in the Fabry trial. The investigational drug product and VCN assay are different for each trial.

"We believe these data are an early, but exciting, validation of our decision to invest in technological innovation rather than build expensive bricks-and-mortar manufacturing facilities," said MacKay. "The plato platform gives us control over the production and scaling of our investigational gene therapies through an efficient, automated manufacturing system that is designed to be deployed in standard contracted sites around the world. The four-plasmid vector, conditioning regimen with precision dosing and other elements of plato are designed to optimize the safety, potency and durability of our investigational lentiviral gene therapies."

About AVROBIOs ex vivo approach to gene therapyOur investigational ex vivo gene therapies start with the patients own stem cells. In the manufacturing facility, a lentiviral vector is used to insert a therapeutic gene designed to enable the patient to produce a functional supply of the protein they lack. These cells are then infused back into the patient, where they are expected to engraft in the bone marrow and produce generations of daughter cells, each containing the therapeutic gene. This approach is designed to drive durable production of the functional protein throughout the patients body, including hard-to-reach tissues such as the brain, muscle and bone. It is a distinguishing feature of this type of gene therapy that the corrected cells are expected to cross the blood-brain barrier and thereby potentially address symptoms originating in the central nervous system.

Lentiviral vectors are differentiated from other delivery mechanisms because of their large cargo capacity and their ability to integrate the therapeutic gene directly into the patients chromosomes. This integration is designed to maintain the transgenes presence as the patients cells divide, which may improve the expected durability of the therapy and potentially enable dosing of pediatric patients, whose cells divide rapidly as they grow. Because the transgene is integrated ex vivo into patients stem cells, patients are not excluded from receiving the investigational therapy due to pre-existing antibodies to the viral vector.

Analyst and investor event and webcast informationAVROBIO will host an analyst and investor event today, Monday, Feb. 10, 2020, in conjunction with the WORLDSymposiumTM, an annual scientific meeting dedicated to lysosomal disorders, in Orlando, FL. The presentation at the event will be webcast beginning at 7:00 p.m. ET. The webcast and accompanying slides will be available under "Events and Presentations" in the Investors & Media section of the companys website at http://www.avrobio.com. An archived webcast recording of the event will be available on the website for approximately 30 days.

About AVROBIOOur mission is to free people from a lifetime of genetic disease with a single dose of gene therapy. We aim to halt or reverse disease throughout the body by driving durable expression of functional protein, even in hard-to-reach tissues and organs including the brain, muscle and bone. Our clinical-stage programs include Fabry disease, Gaucher disease and cystinosis and we also are advancing a program in Pompe disease. AVROBIO is powered by the plato gene therapy platform, our foundation designed to scale gene therapy worldwide. We are headquartered in Cambridge, Mass., with an office in Toronto, Ontario. For additional information, visit avrobio.com, and follow us on Twitter and LinkedIn.

Forward-Looking StatementsThis press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as "aims," "anticipates," "believes," "could," "designed to," "estimates," "expects," "forecasts," "goal," "intends," "may," "plans," "possible," "potential," "seeks," "will," and variations of these words and phrases or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy for and the potential therapeutic benefits of our prospective product candidates, the design, commencement, enrollment and timing of ongoing or planned clinical trials, clinical trial results, product approvals and regulatory pathways, and anticipated benefits of our gene therapy platform including potential impact on our commercialization activities, timing and likelihood of success. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early-stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.

Any forward-looking statements in this press release are based on AVROBIOs current expectations, estimates and projections about our industry as well as managements current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of AVROBIOs product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators, the risk that AVROBIO may not successfully recruit or enroll a sufficient number of patients for our clinical trials, the risk that AVROBIO may not realize the intended benefits of our gene therapy platform, including the features of our plato platform, the risk that our product candidates or procedures in connection with the administration thereof will not have the safety or efficacy profile that we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving AVROBIOs product candidates, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and growth potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIOs actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled "Risk Factors" in AVROBIOs most recent Quarterly Report on Form 10-Q, as well as discussions of potential risks, uncertainties and other important factors in AVROBIOs subsequent filings with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200210005767/en/

Contacts

Investor Contact: Christopher F. BrinzeyWestwicke, an ICR Company339-970-2843chris.brinzey@westwicke.com

Media Contact: Tom DonovanTen Bridge Communications857-559-3397tom@tenbridgecommunications.com

Continued here:
AVROBIO Presents Positive Initial Data for its Investigational Cystinosis Program and Plato TM Platform, as well as Positive Data Out to 32 Months for...

(The Conversation is an independent and nonprofit source of news, analysis and commentary from academic experts.)

(THE CONVERSATION) An emergency room physician, initially unable to diagnose a disoriented patient, finds on the patient a wallet-sized card providing access to his genome, or all his DNA. The physician quickly searches the genome, diagnoses the problem and sends the patient off for a gene-therapy cure. Thats what a Pulitzer prize-winning journalist imagined 2020 would look like when she reported on the Human Genome Project back in 1996.

The Human Genome Project was an international scientific collaboration that successfully mapped, sequenced and made publicly available the genetic content of human chromosomes or all human DNA. Taking place between 1990 and 2003, the project caused many to speculate about the future of medicine. In 1996, Walter Gilbert, a Nobel laureate, said, The results of the Human Genome Project will produce a tremendous shift in the way we can do medicine and attack problems of human disease. In 2000, Francis Collins, then head of the HGP at the National Institutes of Health, predicted, Perhaps in another 15 or 20 years, you will see a complete transformation in therapeutic medicine. The same year, President Bill Clinton stated the Human Genome Project would revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.

It is now 2020 and no one carries a genome card. Physicians typically do not examine your DNA to diagnose or treat you. Why not? As I explain in a recent article in the Journal of Neurogenetics, the causes of common debilitating diseases are complex, so they typically are not amenable to simple genetic treatments, despite the hope and hype to the contrary.

There are indeed individual gene mutations that cause devastating disorders, such as Huntingtons disease. But most common debilitating diseases are not caused by a mutation of a single gene. This is because people who have a debilitating genetic disease, on average, do not survive long enough to have numerous healthy children. In other words, there is strong evolutionary pressure against such mutations. Huntingtons disease is an exception that endures because it typically does not produce symptoms until a patient is beyond their reproductive years. Although new mutations for many other disabling conditions occur by chance, they dont become frequent in the population.

Instead, most common debilitating diseases are caused by combinations of mutations in many genes, each having a very small effect. They interact with one another and with environmental factors, modifying the production of proteins from genes. The many kinds of microbes that live within the human body can play a role, too.

Since common serious diseases are rarely caused by single-gene mutations, they cannot be cured by replacing the mutated gene with a normal copy, the premise for gene therapy. Gene therapy has gradually progressed in research along a very bumpy path, which has included accidentally causing leukemia and at least one death, but doctors recently have been successful treating some rare diseases in which a single-gene mutation has had a large effect. Gene therapy for rare single-gene disorders is likely to succeed, but must be tailored to each individual condition. The enormous cost and the relatively small number of patients who can be helped by such a treatment may create insurmountable financial barriers in these cases. For many diseases, gene therapy may never be useful.

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The Human Genome Project has had an enormous impact on almost every field of biological research, by spurring technical advances that facilitate fast, precise and relatively inexpensive sequencing and manipulation of DNA. But these advances in research methods have not led to dramatic improvements in treatment of common debilitating diseases.

Although you cannot bring your genome card to your next doctors appointment, perhaps you can bring a more nuanced understanding of the relationship between genes and disease. A more accurate understanding of disease causation may insulate patients against unrealistic stories and false promises.

Read more from the original source:
Why sequencing the human genome failed to produce big breakthroughs in disease - Idaho Press-Tribune

AI and gene therapy could help cure AIDS and understand human biology, Bill Gates says.

Microsoft founder Bill Gates thinks artificial intelligence and gene therapy are the two technologies with the greatest power to change lives. In a speech being delivered Feb. 14 at the American Association for the Advancement of Science, Gates said AI can "make sense of complex biological systems," while gene-based tools have the potential to cure AIDS.

The potential of AI is only just being realized now, the billionaire philanthropistsaid Friday, with computational power doubling every 3.5 months. Along with improvements in handling data, Gates said it's enabling "the ability to synthesize, analyze, see patterns, gain insights and make predictions across many, many more dimensions than a human can comprehend."

Gates said the most exciting part of AI "is how it can help us make sense of complex biological systems and accelerate the discovery of therapeutics to improve health in the poorest countries."

Gene-editing technologies will meanwhile help with vaccines, diagnostics and therapeutics, he said. "[It] has the potential to improve health -- not only for rare genetic disorders, but also for diseases that predominately afflict people in poor countries."

Gates also addressed the deadly coronavirus, saying these two technologies could help with diagnostic tests, treatment and vaccine development.

"Our foundation has committed up to $100 million to address this new coronavirus because we believe it poses a serious threat to global health," Gates said. "This money will support efforts to detect, isolate and treat confirmed cases, help countries in sub-Saharan Africa and South Asia take steps to prepare for the epidemic and protect their most vulnerable citizens, and accelerate the development of vaccines, treatments and diagnostics."

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Bill Gates: AI and gene therapy have the power to save lives - CNET

Researchers at the University of Pennsylvania and Childrens National Hospital in Washington, DC utilized a hybrid approach that combined gene therapy with gene editing to treat a rare genetic disease in animal models, making it convert into a milder, more treatable form of the disease. The disease was ornithine transcarbamylase deficiency (OTCD), which is the most common type of a family of illnesses called urea cycle disorders.

Urea cycle disorders affect about 1 in 30,000 individuals. It causes problems in how the body metabolizes proteins in food. Normally, proteins are broken into individual amino acids. The body then recycles those amino acids to create new proteins for the body to use. Extra proteins are metabolized for energy, which requires a chemical category called amines to be removed, which are converted into ammonia. Ammonia is toxic to cells. In healthy people, urea cycle enzymes from the liver convert ammonia into urea, which is harmlessly excreted in urine.

When people have urea cycle disorders, ammonia builds up, causing vomiting and lethargy. If untreated, it can cause coma and death.

The various urea cycle disorders are caused by various genetic mutations. The researchers, led by James M. Wilson at the University of Pennsylvania and Mark L. Batshaw at Childrens National, originally attempted a typical form of gene therapy in animal models, inserting a properly functioning version of the OTC gene into a virus that carries the code for the missing enzyme, ornithine transcarbamylase.

This approach worked in older animals but did not last long in newborn animals because of rapid liver growth. CRISPR/Cas9 gene editing, on the other hand, can be used to modify the genes. Alone, this is a problem for OTCD because there are more than 400 different known mutations that cause it.

For their new approach, which they described in the journal Science Advances, they developed a viral vector that carried an enzyme that creates a targeted break in DNA. This step is typical in standard gene editing. But, instead of correcting the mistake, a second vector that carried a copy of the correct OTC gene sequence was used simultaneously.

In their experimental animal models of newborn animals, the gene integrated into cells and spread in patches in the animals livers as they grew. They produced more and more of the necessary detoxifying enzyme as they grew. They then tested nitrogen loads on the animals, and the ones who had been treated with the combined strategy had approximately 60% lower ammonia levels in their blood compared to untreated animals. All of the treated animals survived a seven-day test, while only a quarter of the untreated animals survived.

Theoretically, this could be a curative approach for OTCD, Batshaw said. And if it worked for that, we could create similar templates to treat other related disorders.

Currently, treatment for the disease includes a very low protein diet, drugs that scavenge nitrogen from the blood or a liver transplant in the most serious cases. Through these therapies, weve turned this fatal disease into a chronic one for most patients, Batshaw said. But theres still no curative approach other than liver transplantation.

The research isnt quite ready for human studies, but it is promising.

Read more:
Hybrid Gene Therapy Approach Shows Promise in Treating Metabolic Diseases - BioSpace

Have you ever slipped when trying to avoid sugar, quit smoking, or break another habit or addiction? Usually that one piece of cake or one cigarette wont ruin your whole plan, but for people struggling with cocaine addiction, one slip can undo months of hard work.

Cocaine consumption is increasing, with 2.2 million people in the U.S. admitting to recent cocaine use in 2017. In 2014, the National Survey on Drug Use and Health estimated that nearly 1 million Americans were addicted to cocaine. The effect of cocaine on the brain and body is so powerful that, even after state-of-the-art treatments, many people trying to quit cocaine relapse within a year.

What if cocaine could be made less euphoric, so that a single use by a recovering addict doesnt result in a full-blown relapse? Scientists at the Mayo Clinic recently published progress toward making this idea a reality a gene therapy that would treat cocaine addiction by making cocaine less rewarding.

We are a molecular biologist and a neurobiologist who are interested in understanding and treating human disease, including neurological disorders such as cocaine addiction. As University of Tennessee faculty members leading basic biomedical research, we have worked for years on how genes are turned on and off in people and the effects of cocaine on mice, respectively. So, we were excited to see a promising convergence of novel gene therapy and cocaine addiction therapy.

A treatment to make cocaine less addictive

Beginning more than 20 years ago, scientists have worked to engineer a new version of a human protein that could break down cocaine so quickly that it doesnt produce an addictive high. We all have the normal human protein BChE that helps regulate neurotransmitters, and which can slowly break down cocaine. Targeted mutations in BChE can turn it into a super-CocH a protein that can quickly break down cocaine. When this CocH is injected into the bloodstream, it breaks down cocaine very fast before the user can experience the pleasurable effects so a dose of cocaine is less rewarding. Being less rewarding means it is easier to stop using cocaine.

Previous research has shown that injections of the super-CocH protein drastically decrease addictive behavior in cocaine-addicted rats. Thats great. But the problem is that daily CocH injections would be too expensive and difficult to maintain for the years needed to prevent cocaine relapse for human users. It would be much more practical to provide a single treatment that could provide enough CocH to last for years.

One way to do that is gene therapy: Give patients the DNA sequence (the gene) that contains the instructions for making super-CocH so their bodies can keep making it for months or potentially years. Fortunately, over the past decade, this type of gene therapy has been moving from science fiction to hopeful reality. Clinical trials have demonstrated the potential of gene therapy to treat diseases from hemophilia to neurodegenerative disorders, and a handful of these are FDA-approved. The new Mayo Clinic study takes an important step toward making CocH gene therapy a reality.

How does gene therapy work?

How exactly does a scientist give a person a gene? You cant just swallow DNA the way you would a pill. The Mayo Clinic scientists had to find a way to deliver the gene to every cell in the liver. The way they did this was to insert the gene for super-CocH into a virus called adeno-associated virus (AAV). AAV has been modified so that when it infects cells it cannot reproduce in the body or make someone sick. It is just a delivery vehicle. The virus works by delivering the CocH gene to liver cells, where it remains for months or years. The cells read the super-CocH gene and use it to manufacture many copies of the CocH protein, which then breaks down cocaine.

In the new study, the team tested this approach in mice. The results are very promising and suggest that this gene therapy is safe and effective. Mice receiving the gene therapy alone were healthy. Mice given cocaine became hyperactive and showed signs of liver damage. When the mice were given cocaine plus gene therapy they behaved normally, as if they had not been given the drug. The cocaine was quickly broken down by their new super-CocH proteins, and their livers showed no signs of damage.

The results are promising enough that the FDA has approved plans to proceed with human clinical trials.

Looking forward

Keep in mind, this treatment wont hit the market anytime soon. It took six years from initial tests of AAV-CocH therapy in mice to reach the point where the technique is safe enough for human trials. There are many aspects of the treatment that need to be evaluated and modified to make sure it is both safe and effective in humans.

For example, AAV gene therapy can produce unwanted immune responses in people that will need to be carefully monitored. Issues such as discomfort caused by the therapy, different responses based on an individuals genetic makeup and interactions with other medications or medical conditions will also need to be addressed.

Because this study only monitored mice for two months, longer-term effects of the gene therapy will need to be investigated. Also, how well this therapy works to treat cocaine addiction in mice is not really known, and treating addiction in humans is certain to be even more complicated.

This gene therapy could someday make a dose of cocaine less rewarding, but a full recovery from addiction will likely require a combination of treatments administered over many years.

Like many, the two us have family members or friends who struggle with addictions that cannot be cured simply by trying harder. This recent work combines careful scientific progress with a creative new idea, giving hope to those trying to overcome cocaine addiction.

Rachel Patton McCord, Assistant Professor of Biochemistry & Cellular and Molecular Biology, University of Tennessee and Rebecca A. Prosser, Professor of Biochemistry & Cellular and Molecular Biology, University of Tennessee

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Image: Reuters

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This Genius Gene Therapy Plan Could Combat Cocaine Addiction - The National Interest Online

To date, the FDA has approved four gene therapy products, which insert new genetic material into a patients cells. The agency anticipates many more approvals in the coming years, as evidenced by the more than 900 investigational new drug (IND) applications for ongoing clinical studies in this area. The FDA believes this will provide patients and providers with increased therapeutic choices.

In that spirit, [January 28], the FDA is announcing the release of a number of important policies: six final guidances on gene therapy manufacturing and clinical development of products and a draft guidance, Interpreting Sameness of Gene Therapy Products Under the Orphan Drug Regulations.

The six guidance documents incorporate input from many stakeholders and take a significant step toward helping to shape the modern structure for the development and manufacture of gene therapies.

In sum, these policy documents are representative of efforts to help advance product development in the field of gene therapy. We will continue to work with product innovators, sponsors, researchers, patients, and other stakeholders to help make the development and review of these products more efficient, while putting in place the regulatory controls needed to ensure that the resulting therapies are both safe and effective.

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900 gene therapy drugs are in the pipeline. How does the FDA want to regulate them? - Genetic Literacy Project