Posts Tagged ‘gene therapy’
Science Policy Around the Web April 27, 2021
By Tony Patelunas, PhD, PhD
Bill Gates wants Western countries to eat ‘synthetic meat’; Meatable has raised $47 million to make it
In an effort to combat impending climate change, Bill Gates, the Microsoft founder and world’s third wealthiest man, is advocating for a shift away from traditional sources of meat. Startups from across the world, many in the United States, have moved towards a solution: lab-grown meat. Two of the best funded companies in this space, Mosa Meat and Meatable (both from the Netherlands) have raised over $40M in financing.
However, the biggest hurdles come after the funding is secured. Meatable plans to have a product ready for European regulatory review in 2023, but Gates’ questions whether cellular agriculture will ever reach economical scales. Meatable is currently spending about $10,000 per pound of meat produced, which is not suitable for large-scale production. If companies in this space can scale up and reduce costs, the reduction in traditional pork and beef consumption can have a major impact on land management and the environment.
With such potential, the companies in this space have attracted major investors includes Dr. Rick Klausner, former Chief Medical Officer of Illumina, Dr. Jeffrey Leiden, executive chairman of Vertex Pharmaceuticals, and institutions such as Section 32, BlueYard Capital, and Agronomics. The investors see this industry as a great opportunity to address existential issues such as food insecurity and the climate crisis.
(Jonathan Shieber, TechCrunch)
She’s 14 months old and needs a drug that costs $2.1 million to save her life
For parents of a child with spinal muscular atrophy (SMA), a genetic disease that causes neural degeneration in early childhood, a life-saving treatment is a race against time. Zolgensma, a single-dose treatment produced by Novartis Gene Therapies, costs $2.1 million and is only approved in the United States for children under 2 years old. For 14-month-old Ayah Lundt, the lack of drug approval in Denmark’s healthcare system and the short time to raise $2.1 million for treatment in the United States had her family turn to a GoFundMe campaign, Friends of Little Ayah, to access this treatment.
Some might wonder why the drug costs $2.1 million when it is just a single injection. Novartis says the cost is in line with the value. Current treatments for SMA can cost up to $6 million for the first 10 years of a child’s life. If Zolgensma works, $2.1 million is far less. Moreover, Novartis has pledged 100 free doses distributed in a lottery style program for SMA patients most in need. Unfortunately, Ayah’s parents are not eligible for the lottery because Zolgensma is not approved for use in Denmark and has yet to receive approval for funding from the Danish Medicines Council.
Until then, the girl who was eating mushy bananas and crawling happily at 6 months is fighting for her life. Daily routines involve continuous positive airway pressure (CPAP) treatment, monthly lumber punctures of different medicines, and some activities to try and strength her muscles. Her parents say she often tries to do more from her small green wheelchair but can’t.
(Faith Karimi, CNN)
Science Policy Around the Web March 24th, 2020
By Maria Disotuar, PhD
The Secretive Company That Might End Privacy as We know It
Have you heard of the start-up company Clearview AI? If not, you’re not alone. Most individuals have not heard about this tiny company, and yet it’s bound to transform our privacy and the world. Clearview is a facial recognition application founded by Hoan Ton-That, an Australian computer programmer and part-time model. The app allows users to upload a picture of a stranger and then it searches a database containing more than 3 billion images scraped from social media sites such as Facebook, Venmo, YouTube, and Instagram. The search results provide images of the stranger and direct links to the photos. The app software also has the capability to be paired-up with augmented-reality glasses which means you could identify anyone on the street and know who they are and where they live in seconds.
For now, the app has only been distributed to Homeland Security, the FBI, local cops, and a few companies for security purposes. These individuals have used the app to solve a series of murder, identify theft, and kidnapping cases. Yet, experts are concerned about future implications of the app and some argue it should be banned all together. Currently, the app has not been tested by an independent party and so there is no data to determine the rate of false or positive matches. Importantly, these types of apps tend to be controversial because they tend to deliver false matches for certain ethnic groups, particularly individuals of color. To date, there is no clear indication about if or when Clearview will be made publicly available, however, experts like Al Gidari, a privacy professor at Stanford University note that without a strong federal privacy law Clearview could end anonymity as we know it.
(Kashmir Hill, The New York Times)
CRISPR treatment inserted directly into the body for the first time
For the first time in history, CRISPR-Cas9 gene-editing has been directly administered into a clinical trial patient to treat Leber’s congenital amaurosis 10 (LCA10), a rare genetic eye disorder that often leads to blindness in infancy. Typically, clinical trials that use CRISPR edit the genome of cells removed from the body. The CRISPR elements are introduced into the cells and then these cells are transplanted into the patient. In this case, however, the CRISPR elements are injected directly into the eye and used to remove the mutation in the gene CEP90 that results in LCA10.
This is not the first time gene editing has been used directly on a clinical trial patient. In 2018, Sangamo Therapeutics used an older gene editing system called zinc-finger nucleases to alleviate the symptoms of Hunter’s syndrome, a metabolic disease that can lead to organ damage. The results of the trial showed that the therapy was not effective. CRISPR, however, is more powerful and easier to use and design in the laboratory. Scientists hope direct insertion of CRISPR elements will remove the DNA mutation and lead to reactivation of the inactive photoreceptors.
Yet, this landmark event does not come without challenges. There are inherent safety and efficacy concerns when using this type of technology directly on an individual. The challenge with direct application is getting the CRISPR system to edit the correct place and understanding if the system made unwanted off-target edits. For now, the first volunteers to get the therapy will receive a small dose to test for efficacy and later they will receive larger doses to minimize any health risks.
(Heidi Ledford, Nature)
Science Policy Around the Web December 6th, 2019
By Hannah King, PhD
200,000 Uninsured Americans to Get Free H.I.V.-Prevention Drugs
World AIDS Day, held annually on December 1st, has led to a flurry of AIDS-related announcements this week.
The Trump administration has released an announcement outlining how it plans to distribute HIV prevention drugs donated by the pharmaceutical company Gilead, which manufactures the drugs. These drugs will be available to 200,000 uninsured Americans who have a prescription and recent evidence of their HIV-negative status.
While other programs exist in the US to provide these drugs free of charge (including those run by cities in high-incidence areas and a program from Gilead itself) this announcement marks the first time the government has provided such HIV-prevention medicine free to individuals not enrolled in a federal health program. With 37,500 new HIV infections per year in the US, and 1.2 million Americans estimated as being at high risk for HIV-acquisition, widespread distribution of this preventative treatment is an important public health initiative.
Access to HIV prevention and treatment medication is also a worldwide issue. In further encouraging news, an Indian drug manufacturer has announced that it will make a pediatric formulation of HIV medication, that is strawberry flavored and the size of sugar granules! The current medication is either formulated as hard tablets, or requires refrigeration, reducing either the tolerability to children or accessibility of the product. As 160,000 children are born with HIV each year, but only approximately half receive treatment, this new formulation will hopefully reduce the AIDS-related morbidity and mortality in this vulnerable population.
(Donald G. McNeil Jr., New York Times)
China’s CRISPR babies: Read exclusive excerpts from the unseen original research
Further details of the research purporting to use CRISPR to create gene-edited babies have emerged, reinforcing the “serious, unresolved safety concerns” associated with this human research.
MIT Technology Review has released excerpts from an unpublished manuscript outlining a study by the Chinese researcher He Jiankui which describes the creation of the first gene-edited human babies. The mutation introduced into the embryos is a deletion in the gene expressing a protein called CCR5. A deletion in this CCR5 protein occurs naturally in some individuals and renders them resistant to infection with HIV – the stated rationale for this experiment. However, the manuscript shows the deletion that was introduced into the genomes of these babies is similar, but not identical to the naturally occurring deletion, and no attempt is made by the authors to validate its ability to confer HIV resistance.
Furthermore, despite the manuscript describing the experiments a “success”, the data shows the CCR5 deletion is absent in one chromosome on one of the babies, meaning she carries one copy of the functional CCR5 gene, and is still susceptible to HIV infection. Data in the manuscript, showing DNA sequencing of cells from the babies following their birth also indicates that not all cells in these babies share the same genetic code, suggesting that not all cells carry the CCR5 deletion, or that other “off-target” effects with unknown health implications may be present.
This newly available data, in addition to the many ethical concerns previously raised, further demonstrate this experiment is not the “success” nor the path forward to “control the HIV epidemic” that He Jiankui claims it to be.
(Antonio Regalado, MIT Technology Review)
Science Policy Around the Web September 3rd, 2019
By Ben Wolfson PhD
Biohackers are pirating a cheap version of a million-dollar gene therapy
This past weekend, the 4th annual Biohack the Planet, a conference for community scientists and biohackers, was held in Las Vegas. In addition to discussions concerning the future and goals of biohacking, a group of biohackers announced their efforts to develop a pirated version of the gene therapy Glybera, called Slybera.
First approved in Europe in 2012, Glybera is a gene therapy meant to treat the rare genetic disorder lipoprotein lipase deficiency (LPLD). Glybera provided a “one-off” solution to LDLD by inducing a patients body to produce new copies of the missing protein. Approximately 1 in every million people suffer from LPLD, meaning that there existed an exceedingly small market for the drug. Moreover, upon its release it was deemed the world’s most expensive drug at approximately 1 million dollars per dose. Due to financial issues associated with this high cost, Glybera was withdrawn from market in 2017.
At Biohack the Planet, research leader Gabriel Licinia described the process of creating a prototype pirated version of Glybera, which he says cost less than $7,000 and was created in only 2 months. Licinia and his colleagues got the gene sequence used in Glybera from the original papers published describing it, and ordered the DNA from a commercial DNA synthesis company. They then inserted the DNA into a genetic construct capable of inducing mammalian cells to produce the LPL protein.
While Licinia demonstrated that this method works in cells, it would likely not have the same long lasting effects as Glybera, which uses viruses as carriers for the LDL gene, producing stable expression of the protein for a number of years.
The future of Slybera is uncertain, as there is currently no defined clinical path for products created by biohackers. However the team is taking steps to demonstrate their seriousness, including distributing their materials to fellow biohackers so they can attempt to replicate their studies.
(Alex Pearlman, MIT Technology Review)
Gene editing- Regulatory and ethical challenges
By: Chringma Sherpa, Ph.D.
When power is discovered, man always turns to it. The science of heredity will soon provide power on a stupendous scale; and in some country, at some point, perhaps, not distant, that power will be applied to control the composition of a nation. Whether the institution of such control will ultimately be good or bad for that nation, or for humanity at large, is a separate question.
—William Bateson, English biologist who coined the term “genetics.”
On November 25, 2018, in an allegedly leaked YouTube video, He Jiankui, a scientist at the Southern University of Science and Technology in Shenzhen, China, revealed the birth of the first gene-edited babies using a technology called CRISPR. There has been a general consensus in the scientific community that heritable changes should not be made to prevent the off-target and unwanted genetic changes artificially produced in an individual during gene editing to be passed on to his/her offspring(s). He became the first scientist to publicly violate this consensus resulting in an international scandal and criminal/ethics investigations into both He and his collaborators.
In the wake of He’s CRISPR-babies scandal, scientists worldwide are debating on the ethical and regulatory measures that would discourage another wayward and rogue scientist like He from attempting such an irresponsible feat. At the 2nd international summit on human gene editing that convened two days after He’s video became public, He presented his work. The summit was well attended by ethicist and journalist besides scientists. At the summit, David Baltimore of the California Institute of Technology, who chaired the organizing committees for both the 1st and 2nd international summits on human gene editing read one of the conclusions from the 1st summit held at Washington DC in 2015 – “It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application”. Baltimore called He’s work outright irresponsible on the basis of the statement from the 1st summit. At the summit, many other ethical and safety-related questions were raised which He failed to answer or did not answer convincingly.
He’s scandal has driven various organizations to draft new guidelines and sanctions aimed at preventing unethical and unapproved use of genome editing. China has imposed new laws requiring human gene editing projects to be approved by China’s health ministry first to avoid fines and blacklists. Both the 2nd human gene editing summit and the WHO panel that convened in March 2019, have proposed a central registry of human gene-editing research and called for an international forum/ committee to devise guidelines for human gene editing based on common norms and differences of opinions between countries. To allow time for the creation and effective implementation of new regulations, the WHO also called for a global moratorium on heritable editing of human eggs, sperm, or embryos for the next five years. Supporting the WHO panel’s recommendations, Francis Collins, director of the National Institute of Health, said that “NIH strongly agrees that an international moratorium should be put into effect immediately”. However, not all scientists are in favor of a moratorium, as they believe it might stifle the growth of a technology that might be safe and beneficial in the near future. Jennifer Doudna of the University of California, Berkley, one of the co-inventors of CRISPR gene editing, says that she prefers strict regulation that precludes the use of germline editing until scientific, ethical, and societal issues are resolved over a moratorium. David Baltimore agrees with Doudna stating that the word moratorium was intentionally not used in both the human gene editing summits as a moratorium would be hard to reverse. Science historian Ben Hurlbut of Arizona State University, who had numerous discussions with He before Lulu and Nana were created, thinks a blanket moratorium on clinical germline editing would have prevented He from proceeding. Both the two human gene editing summits and a 2015 essay by Baltimore, Doudna, and 16 co-authors had already outlined numerous guidelines for clinical germline editing. According to Hurlbut, He weighed these criteria and believing that his procedure met all the guidelines proceeded. A categorical prohibition of germline editing would not have allowed him to use his subjective judgment and act out of self-interest.
The modern debate over CRISPR editing is not the first time the scientific community has come together to discuss game-changing biological technologies, and it is heavily informed by two prior events. In 1970, Paul Berg and his postdoctoral researcher David Jackson used the recombinant DNA technology to create the first chimeric DNA. This invention created an uproar among the scientists and the general public who feared that this technology would lead to the creation of uncontrollable and destructive superbugs, the exaggerated versions of which can be seen in some science fiction movies. Yielding to the opinions and sentiments of the fellow scientists, Berg held himself from cloning such recombinant DNAs and in 1974, he pleaded for a voluntary moratorium on certain kinds of recombinant DNA research until their safety issues have been resolved. He also moved quickly to organize the Asilomar conference (Asilomar II) in 1975 that bore semblance to the 2nd human gene editing conference in that it invited not only the scientists but lawyers, ethicists, writers, and journalists to weigh in on the risk-benefit analysis of the Recombinant DNA technology. On the recommendation of Asilomar conference, Donald Fredrickson, then director of the National Institutes of Health (NIH), initiated the formation Recombinant DNA Advisory Committee (RAC) to act as a gatekeeper of all research that involved recombinant DNA technology. The scope of the committee, which was composed of stakeholders, including basic scientists, physicians, ethicists, theologians, and patients’ advocates was later expanded to encompass the review and approval of human gene therapy research. Due to the redundancies of regulatory oversights between the US Food and Drug Administration (FDA) and RAC, RAC was reinstated as only an advisory body providing advice on the safety and ethical issues associated with emerging biotechnologies in 2019.
While this is a successful example of scientific self-regulation, the second event resulted in a major setback in the field of gene therapy. On September 13, 1999, Mark Batshaw and James Wilson of University of Pennsylvania supervised the administration of adenovirus to an 18-year-old Jesse Gelsinger in a gene therapy clinical trial. Gelsinger died of liver and kidney failure and brain damage three days later. Like the birth of CRISPR babies, Gelsinger’s death was an instance where new technology was used prematurely without a thorough assessment of its safety profile. It is suspected that both the clinical applications headed by He and Wilson might also have been motivated by fame and financial gain; He and Wilson both had financial stakes in private biotechnology companies that would benefit from these human trials. In the aftermath of Gelsinger’s death, Wilson was banned from carrying out FDA regulated clinical trials for the next five year, nearly all gene therapy trials were frozen, and many biotechnology companies carrying out these trails went bankrupt. This was a dark period in the history of gene therapy, and it would take almost another decade of introspection, reconsideration, and more basic experimentation for gene-therapy to re-emerge as a viable therapeutic strategy.
Scientists at both the Asilomar and human gene editing conferences passionately debated the safety of the relevant technologies but deliberated on the discussion of the big ethical issue associated with these technologies – the ultimate creation of designer babies. That gene editing sits on the slippery slope to eugenics was recognized since the days of Charles Darwin and Gregor Mendel when the study of genes and heredity was still in its infancy and the discovery of DNA as the genetic material was half a century away. One of the earliest proponents of genetic manipulation for human benefits was Francis Galton, Charles Darwin’s cousin. Galton proposed an unnatural and accelerated selection of beneficial traits by marriage between people of desirable traits. The danger that someday some rogue scientists might use germline gene editing technology in favor of eugenics lurks in the mind of those who understand the potential of the currently available gene editing technologies. However, more fearful is the idea that the wave of positive eugenics would soon give way to negative eugenics – elimination of undesirable traits as it did around World War II as exemplified by the famous case of Carrie Buck, a woman who was designated “mentally incompetent” and involuntarily sterilized.
Various countries have their own regulation and legislation on germline editing to prevent any backlash from this powerful technology. Figure 1 presents a summary of the regulatory landscape of germline gene modification surveyed in thirty-nine countries by Araki Motoko and Tetsuya Ishii. In the US, Congress has shown strong support against germline gene editing. In 1996, it passed a rider as part of the annual appropriations bill that prohibits the use of federal funds for any research involving human embryo. In another appropriations bill passed in 2015, Congress banned the FDA from considering applications involving the therapeutic modification of the human germline.
Human gene editing holds great promises in treating many life-threatening and previously intractable diseases. Only when this discipline of science is held to high ethical standards and regulated sensibly at international, national, and a personal level, shall we reap the benefits of this powerful technology.
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Science Policy Around the Web – September 11, 2018
By: Liu-Ya Tang, Ph.D
Source: pixabay
New Therapies
Here’s what we know about CRISPR safety – and reports of ‘genome vandalism’
Since its discovery in 2012, CRISPR-Cas9 has become a popular gene-editing tool forr removing, adding or altering sections of the DNA sequence in the genome. It has been widely used in research settings because it is efficient, precise and cheap. Beyond that, there is a growing interest in applying CRISPR techniques in treating human diseases which are caused by genetic mutations. Firms such as CRISPR Therapeutics, Intellia Therapeutics and Editas Medicine are conducting clinical trials of therapies using CRISPR. For example, one of the pipelines from CRISPR Therapeutics is a gene-editing Phase I/II trial for beta-thalassemia and sickle cell disease, which are caused by mutations in β-globin gene. Hematopoietic blood cells, which are the stem cells that generate red blood cells, are taken from the patient. After genetic correction, the cells are then reintroduced to the same patient. The hope is that the “revised” stem cells will produce normal red blood cells, which will cure the disease, relieving the patients from a lifetime of blood transfusions. Furthermore, there are other clinical trials of treatments for Hemophilia, Duchenne muscular dystrophy and cystic fibrosis by CRISPR. In China the technology has been used to treat patients with oesophagus cancer.
Though there is great potential for applying CRISPR to cure human diseases caused by various genetic mutations, cautionary measures need to be implemented while the safety of this technology is being debated. Several studies have raised concerns that CRISPR may not be as effective as previously thought, and in some cases it may produce unwanted side effects. The data have shown that applying CRISPR-Cas9 system on human body may cause stress to cells and some people may not be responsive to CRISPR-based therapy if their immune system has developed an immune defense against the CRISPR protein. Additionally, studies show that CRISPR-Cas9 may cause off-target DNA damage during genome editing, and the rate is about 1 to 5 percent. However, the clinical application of CRISPR editing is a work in progress. Hopefully new versions of the technique with improved accuracy and efficiency will be used to treat genetic diseases in the near future.
(Jianhua Luo, The Conversation)
Public health
Hospitals are fed up with drug companies, so they’re starting their own
Shortages of critical generic drugs and price spikes on old drugs have plagued hospitals in recent years. To resolve this, a group of major American hospitals are launching a nonprofit and independent generic drug company, which is called Civica Rx.
The company’s mission is to “make sure essential generic medicines are affordable and available to everyone”, so it will focus initially on establishing price transparency and stable supplies for 14 generic drugs used in hospitals. Civica is backed by seven large health systems and three philanthropic groups including Mayo Clinic and HCA Healthcare, collectively representing about 500 hospitals. A commitment of $100 million from governing members have been contributed to the effort, and member health care organizations have agreed to buy drugs from Civica based on the long-term contracts.
The list of 14 drugs haven’t been disclosed because of competitive reasons, but they include generic drugs that underwent price increases of 50 percent or more between 2014 and 2016 and essential medicines that were on national shortage lists. It is estimated that the first drug from Civica could hit the market next year.
The establishment of Civica would present a “threat” to other pharmaceutical companies that make the same generic drugs. There is a possibility that those companies will temporarily cut their prices to maintain the market share. But Civica leaders say the model of guaranteeing a steady supply at a fair, transparent price will be attractive to hospitals. Martin VanTrieste, chief executive of Civica, hopes that the entrance of 14 generic drugs to the market is a good correction for the over-priced drug market and the company would expand if the market place cannot be fixed by adding these 14 drugs.
(Carolyn Y. Johnson, The Washington Post)
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Science Policy Around the Web – October 17, 2017
By: Charles Wright, Ph.D.
Source: Public Domain Pictures
Gene Therapy
FDA experts offer a unanimous endorsement for pioneering gene therapy for blindness
Gene therapy, an approach long hailed for its potential to cure intractable genetic diseases, finally has some successes in getting regulatory approval. Recently, the U.S. Food and Drug Administration (FDA) approved the first-ever gene therapy treatment for a fatal brain disease.
Last week, another gene therapy approach—this time for a blinding disease that strikes in early-to-late childhood—also received endorsement by a 16-0 vote from the FDA’s Cellular, Tissue and Gene Therapies Advisory Committee. The vote provides encouragement for patients suffering from Leber congenital amaurosis, type 2 (LCA2), which Voretigene neparvovec (Luxterna) from Spark Therapeutics aims to treat. However formal regulatory approval is still pending . Leber congenital amaurosis, although rare with an estimated prevalence of only 1:50,000 – 1:100,000, devastates vision at an early age. Newborns may show visual impairment immediately after birth, and most LCA patients lose most of their vision by the time they reach 20-30 years of age. Voretigene neparvovec aims to treat patients with mutations in the RPE65 gene, characteristic of LCA2, through gene therapy.
The recent string of successes in gene therapy comes years after the field struggled to rebuild itself after tragedy. In 1999, the death of a participant in a trial to treat a rare metabolic disorder forced FDA to strengthen its oversight of gene therapy trials. With the first formal FDA approval for a gene therapy awarded just months ago, the recent approvals for other treatments since then suggests gene therapy may have reached a turning point. In the future, gene therapy may be common for a variety of diseases.
If voretigene neparvovec receives FDA approval, it will be the first gene therapy treatment for a blinding disease.
(John Carroll, Science)
The Scientific Workforce
Why I’m pushing for a postdoc union
Postdoctoral fellows face a bevy of obstacles that threaten to derail even the most brilliant and committed young scientists from a research career. Many postdocs unfortunately become intimately familiar with them in the lab; funding, publications, and tenure-track positions elude trainees and can keep postdocs from establishing themselves as independent researchers for years. The harsh reality of the postdoc lifestyle often causes problems outside the lab as well. Low pay, long working hours, and relationship strain all take their toll.
In response to these issues, some postdocs try to form unions to force academia to respond. The subject of postdoc unions often pits researchers against university administrators, and the legal standing of postdoc unionization remains in flux. Universities may claim unionization ultimately harms postdoc employment, as supervisors may write less than glowing recommendation letters for post-docs who missed work due to labor disputes. Nevertheless many postdocs feel unions may help provide a platform for receiving the benefits they need.
Brian Weitzner at the University of Washington (UW) in Seattle proposes collective bargaining rights for postdocs employed at UW campuses across the state. In the past several months, while he and other postdocs prepare for a vote on whether to unionize, he talked with UW postdocs who share his concerns. Fair pay, health insurance, and protection for victims of sexual harassment in the laboratory all motivate him to seek the establishment of a formal avenue with universities for resolving these and other issues.
UW postdocs are working with a local chapter of United Automobile Workers to navigate the steps needed to form a union. Their petition to vote is currently being reviewed by the Washington State Public Employment Relations Commission.
(Brian D. Weitzner, Science Careers)
Genomics
The rise and fall and rise again of 23andMe
Four years ago, the DNA-testing firm, 23andMe, teetered on the edge of oblivion. Then, in 2015, 23andMe made the news again when it announced regulatory approval to sell a test for a rare genetic disease directly to the public. Now, the company offers testing for 10 genetic diseases to consumers and continues to supply genomics data to collaborators to aid in drug development.
In 2007, 23andMe first gained prominence with its home-delivered kit that consumers could use to learn more about their genome. After the company analyzed the data, costumers would receive information about their ancestry, predisposition to disease, and other miscellaneous facts such as whether they carried DNA variants that impacted their earwax consistency or urine smell after eating asparagus. 23andMe would also pool customers’ de-identified data together to analyze and sell to other pharmaceutical companies or research collaborators.
As 23andMe grew in popularity, critics became concerned that consumers were being overly impressed by advertisements indicating they could use their own genetic information to better inform personal health decisions even though many links between the DNA sequence variations reported by the test and disease remain dubious. Alarmed by the possibility patients could make decisions about their health on information that had not been fully validated, FDA warned 23andMe it would need to provide evidence of the accuracy of the tests and ability of consumers to understand the results to continue marketing their kit as a health tool. 23andMe ignored the FDA’s warnings until the regulatory agency finally issued a cease-and-desist letter.
Since then, 23andMe decided to work with the FDA to approve the genetic tests included in its kit. The company can still only sell genetic tests directly to customers for a small number of diseases but is working with the FDA to expand its offerings to the general public. In the meantime, the company still works with research collaborators to find new disease-relevant DNA variations, like those possibly involved in clinical depression.
Ultimately, 23andMe hopes its business model will lead to new therapies for disease.
(Erika Check Hayden, Nature)
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Science Policy Around the Web – October 10, 2017
By: Kseniya Golovnina, PhD.
source: pixabay
Gene Therapy
In a First, Gene Therapy Halts a Fatal Brain Disease
The first historic gene therapy approval by the U.S. Food and Drug Administration in August 2017 opened a new era for the treatment of serious and life-threatening diseases. One month later Bluebird Bio announced the successful start of Lenti-D therapy in the clinical trial and gave a flutter of hope to cure cerebral adrenoleukodystrophy (CALD) also known as Lorenzo’s Oil.
Adrenoleukodystrophy (ALD), a rare disorder that affects one in 21,000 male births worldwide, is caused by mutations in the ABCD1 gene that lead to the subsequent accumulation of very long chain fatty acids in tissues, including the myelin of the central nervous system. The most severe form of ALD, known as cerebral ALD (CALD), involves the progressive destruction of the protective sheath of the nerve cells in the brain that are responsible for thinking and muscle control. This leads to deafness, blindness, seizures, loss of muscle control and dementia, resulting in permanent disability or death. Symptoms of CALD progress rapidly if untreated and the only current treatment is stem cell transplantation.
Gene therapy is a technique for correcting defective genes responsible for disease development. It utilizes viruses to deliver unmutated copies of the genes, such as the ABCD1 gene, to the cells of the patient’s body. First, blood from the patient is collected by apheresis, depleting immune response T cells and enriching progenitors of all blood cells (hematopoietic stem cells, HTS). The HTS cells are then infected with a virus carrying a functional copy of the gene, before returning the cells to the body.
Bluebird Bio is now pursuing Lenti-D therapy which uses lentiviruses to deliver a functional copy of the ABCD1 gene to patients with ALD. Results published in the New England Journal of Medicine, reported that 15 out of 17 patients (88%) were free from major functional disabilities two years after the hematopoietic stem-cell gene therapy. These results demonstrate the therapy’s efficacy over the 76% benchmark established by radiotherapy-free survival at 24 months. Bluebird’s Chief Medical Officer David Davidson expressed excitement about the patients’ progress. He announced that the first four patients treated in the expansion cohort are also doing well, as measured by their amount of the functional ABCD1 gene.
(Gina Kolata, The New York Times)
Drug pricing
FDA acts to encourage generic competition for complex drugs
What kind of feelings do you have when pharmaceutical companies announce their prices for upcoming exciting gene therapies and other innovative, life-changing bio pharmaceuticals? Positive news about development and success of first-of-their-kind drugs can be undermined by anxieties that patients will not be able to afford them. High drug prices can prevent accessibility of new therapies vital for many patients, and market analysts predict rapid inflation in healthcare spending over the next few years due to the aging US population.
The FDA is conscious of the stress expensive drugs put on both patients and the entire healthcare system. Under the leadership of current Commissioner, Dr. Scott Gottlieb, one of key goals of the the FDA is to bring more competition from generics to help drive prices down. On October 2, 2017 the agency prepared draft guidance specifically aimed at copycats of complex therapies and therefore trying to clear the way for generic drug makers to the market.
Gottlieb wrote in his blog post that the agency is looking for more efficient regulatory pathways with robust reviews and communication with pharmaceutical companies for abbreviated new drugs applications (ANDAs). He highlighted that “early and better meetings between FDA and sponsors can improve development timelines. The agency acknowledged that the complexity of the approval process may be discouraging to generic drug makers. The new guidance aims to clarify these complexities by outlining how genetic makers can prove “sameness” by showing that there is no difference in response to generic drug compared with the original. This is the second update for ANDAs process and Dr. Gottlieb assured that FDA will continue to progress in this reformation.
(Linda A. Johnson, The Associated Press)
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Science Policy Around the Web – September 5, 2017
By: Sarah L. Hawes, PhD
Image: By Simon Caulton [CC BY-SA 3.0], via Wikimedia Commons
Gene therapy
FDA approves breakthrough gene therapy for childhood leukemia
Last week, the FDA approved use of gene therapy for the first time, to be used against resistant or relapsed acute lymphoblastic leukemia (ALL) originating in B-cells. The treatment, called Kymriah, was made by Novartis Pharmaceuticals in collaboration with University of Pennsylvania. It is a form of CAR T-cell therapy, in which a patient’s own immune cells are extracted and genetically modified to better identify and attack cancer-laden B-cells before being infused back into the patient.
Because the cellular feature which modified T-cells use to seek and destroy cancerous cells is also present on healthy B-cells, treatment carries risks including hypoxia, hypotension, and suppressed immune function. A life-threatening immunological reaction called cytokine release syndrome appears more commonly in adults, and may explain patient age-restriction (25 and under) on FDA’s approval.
For patients with otherwise intractable cancer, Kymriah may be a literal life-saver. In a recent clinical trial on 63 patients with drug-resistant or recurring ALL, Kymriah lead to remission in 83% of cases three months post-treatment.
While announcing approval of Kymriah, FDA Commissioner Scott Gottlieb asserted that the FDA is “committed to helping expedite the development and review of groundbreaking treatments that have the potential to be life-saving.” This has been substantiated for Kymriah in particular using both Priority Review and Breakthrough Therapy mechanisms. These speed FDA approval, thereby shortening pharmaceutical companies’ delay to profit, and have helped to drive activity in the promising CAR T-cell research arena in recent years.
Despite the success of these mechanisms in bringing a breakthrough cancer therapy to market faster, Novartis insists that a $475,000 price tag for one-time treatment is conservative considering the high cost of drug development and low number of candidate patients. This sobering figure is made worse by the fact that some cases indeed recur several months following Kymriah. Novartis is currently working with Medicare on a plan for outcome-based pricing, so that the pharmaceutical company is only paid if patients respond to the therapy.
(FDA News Release; Jessica Glenza, The Guardian)
Image: By NOAA, via Wikimedia Commons
Emergency preparedness
Hurricane Harvey illustrates the importance of disaster preparedness for research institutions (again)
The US National Academies of Sciences, Engineering, and Medicine released a report just last month highlighting weaknesses in disaster preparedness in biomedical research facilities, and issuing recommendations to enhance the resilience and continuity of research in the face of adversities including natural disasters, fires, and cyber threats. Costs of unpreparedness are high. In In 2012 Hurricane Sandy is estimated to have caused NYU more than $20 million in research equipment, and killed thousands of mice housed in New York laboratories, including many transgenic strains which took decades to develop and existed nowhere else on earth.
Hurricane Harvey’s toll on the scientific community is similarly, incalculably high. University of Houston’s infant rhesus monkeys ran out of formula and had to be weaned early. Loss of refrigeration capability jeopardized precious tissue and reagents, not to mention rendering some agents hazardously unstable. The University of Texas at Austin Marine Science Institute lost the roof off a microbial-ecology lab, forcing trainees to abandon their work and move to alternative institutions.
Some fared better due to advanced planning. For instance, Baylor College of Medicine was protected from Harvey by a wall installed around their campus after 2001 Tropical Storm Allison cost them 60,000 breast-cancer samples and thousands of laboratory animals. To support less fortunate Texas researchers, the broader scientific community has used hashtag #SciHelpTX on Twitter to advertise sharable resources such as open lab space, computers, and animal colony husbandry.
Hopefully Harvey has driven home the message that preparedness is a necessary investment going forward. Enacting preparations remains up to individual institutions’ policies; a list of recommendations by the National Academies can be found here.
(Emma Marris, Nature News)
Image: Wikimedia Commons
Gene therapy
Correction of a pathogenic mutation in human embryos? Maybe! The exploration continues
An August 2017 publication in Nature reports success using CRISPR-Cas9 to delete targeted sections of gene responsible for producing familial hypertrophic cardiomyopathy from human zygotes. The study, led by Dr. Shoukhrat Mitalipov, involved collaboration between the Salk Institute, Oregon Health and Science University (OHSU) and Korea’s Institute for Basic Science. By introducing a short-lived version of CRISPR, an enzyme, and a repair template into a healthy egg prior to fertilization but simultaneously with sperm bearing the targeted genetic defect, authors believe they ensured the gene excisions would take place early, and be carried throughout all following cell divisions. They believe this technique avoids unintended edits and mosaicism, in which both diseased and repaired cells exist side by side in the organism. The team found both the deleted genes and the template for replacement absent, and believe the genome repair used the healthy genes from the egg. They suggest this is due to certain evolutionary resiliencies associated with early stage eggs.
Other researchers responded by emphasizing the remaining uncertainties and importance of maintaining a focus on research as opposed to pushing too quickly toward application of germline editing techniques with the potential for producing heritable genetic changes. Complex ethical questions remain around germline editing even should techniques be perfected for any specific section of the genome. This research could not receive government funding due to the creation and destruction of human embryos.
Within three weeks, a preprint article questioned the likelihood of the egg serving as a template for repair of the genome’s deleted genes. The authors state that following fertilization the egg and sperm DNA are not in close enough contact for such borrowing, and propose two alternative scenarios: Either the egg failed to incorporate the sperm DNA which is sometimes seen with in vitro fertilization, or failed to replace the missing segment at all. Either would have resulted in an absence of the targeted paternal or template genes. Mitalipov has promised to respond point by point.
(Kelly Servick, Science Magazine)
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Science Policy Around the Web – May 13, 2016
By: Danielle Friend, Ph.D.
Gene Therapy Treatment
Gene Therapy Effective in Treating Rare Brain Disorder
A recent study has shown promising results using gene therapy to treat andrenoleukodystrophy (ALD), a genetic disorder that occurs in approximately 1 in 18,000 individuals and is caused by a mutation in a gene on the X chromosome. With ALD, individuals lose the myelin sheath that protects and allows brain cells to function properly. Symptoms of ALD begin between the ages of four and ten and include behavioral issues. Symptoms progress with individuals developing blindness, deafness, seizures, loss of muscle control, and dementia, ultimately leading to death. Until now the only treatment for ALD was a bone marrow transplantation that includes problems related to immune rejections and difficulty matching donors.
Researchers at Bluebird Bio have now tested a gene therapy approach in a trial including 17 children with ALD. Blood from the affected children was removed, the blood cells treated with a virus that expressed the normal ALD protein, and the blood was then reinfused into the patients. According to the report, within 6 months, 16 of the 17 patients symptoms had stabilized. Brains scans conducted 2 years after the reinfusion indicate that the myelin loss stopped progressing. Importantly, none of the patients have shown signs that the gene was inserted into an inappropriate location on the genome, causing serious side effects seen with other gene therapies.
Although these results have lead to a possible therapeutic for halting symptoms, the treatment is unable to reverse the damage to the myelin and thus reverse symptoms that have already manifested. However, the hope is that in the future gene therapy to treat ALD could be used as soon as patients are diagnosed, thus ideally preventing the progression and development of the more severe symptoms.
Bluebird Bio will soon be applying for approval from U.S. Food and Drug Administration (FDA), however a long road to treatment of patients in the United States could be ahead. While authorities in Europe have given approval for the use of gene therapy for rare disorders, the FDA has yet to approved a single gene therapy. This hesitancy from the FDA likely stems from previous side effects and the unfortunately death of Jesse Gelsinger resulting from gene therapy treatment. In addition to the development of an effect means for treating ALD, these gene therapy findings also provide hope for gene therapy techniques in safely treating other diseases in the future. (Jocelyn Kaiser, Science)
Zika Virus
Rapid, Cost Efficient Diagnostic for Zika Coming Soon
Until recently the only means for determining if an individual was infected with Zika was to use a technique known as the Polymerase Chain Reaction (PCR) or antibody detection. Unfortunately the resources to perform these tests are unavailable in many areas. Furthermore, antibodies produced against Zika may cross react with those produced against other similar viruses, thus limiting the specificity of the results. For an example, an individual whom was infected with dengue, when tested using the antibody method, may also test positive for Zika despite never having been infected with Zika. Since the rise in Zika spread there has been an emphasis on the development of a diagnostic test that would allow individuals all over the country (and world) to easily and quickly be tested for the virus.
Last week, a consortium of researchers including scientists from Harvard, Massachusetts Institute of Technology, Cornell, Arizona State, and Boston University all led by Dr. James Collins, a synthetic biologist at Harvard announced that they may developed such a test. The new test, which can develop results in two to three hours is not only faster and potentially more accurate than current methods but is also much cheaper and the result can be easily read. The test is paper-based and consists of a series of yellow dots that change to the color purple when placed in contact with Zika virus RNA.
While the test has not yet been tested with human samples, it has successfully detected Zika virus in the blood of infected monkeys. Dr. Francis Collins, the director of the National Institutes of Health stated that they are now working with groups in Colombia and Brazil to test the diagnostic in the field. Additionally the researchers state that they hope the new test will not only reduce future spread of Zika but other possible diseases as well by paving the way for a rapid, low-cost diagnostics. (Donald McNeil Jr., New York Times)
Public Health Policy
Food and Drug Administration Begins Regulating E-Cigarettes
The first piece of legislation aimed at regulating e-cigarettes was issued last week when the Food and Drug Administration (FDA) made the sale of e-cigarettes illegal to those under the age of 18. According to the Center for Disease Control and Prevention, approximately 5.3 percent of middle school and 16 percent of high school students reported using e-cigarettes in the past 30 days, a statistic that has risen in the last couple of years.
While public health experts support the new regulations, they also call for the FDA to do much more, suggesting that increased regulation on advertising for e-cigarettes and the ban of e-cigarette flavors that appeal to children including bubble gum, chocolate, and cotton candy should be put in place. In contrast, the e-cigarette industry and others are concerned that the new regulations will make it harder for consumers to obtain less harmful alternatives to traditional cigarettes. In fact, David Levy, professor in the department of oncology at Georgetown Lombardi Comprehensive Cancer Center believes that there is strong evidence that e-cigarettes may help addicted individuals stop smoking and the new regulations may be prohibitive for individual who use traditional cigarettes from quitting.
In addition to banning sales for individuals under 18, the new regulations also call for e-cigarette manufactures whose products went on sale after February 15th 2007 to seek approval from the FDA before they begin selling their products. The FDA also states that the new approval requirement will allow the FDA to verify e-cigarette ingredients and evaluate possible health risks. The American Vaping Association stated in response “This is not regulation — it is prohibition,” further emphasizing that submitting an application for approval takes more than 1,700 hours and cost upwards of $1 million. Retailers are also banned from selling e-cigarettes in vending machines that minors have access to and from distributing free e-cigarette samples. The FDA also suggests that they may soon ban e-cigarette flavors that are specifically targeted to children.
No doubt this will not be the last we hear of this battle between the e-cigarette industry and the FDA, Nicopure Labs LLC, a manufacturer of e-cigarette products, announced Tuesday that it has filed a lawsuit in the federal district court in Washington, D.C., challenging the FDA’s regulations. (Laurie McGinley and Brady Dennis, Washington Post)
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Science Policy For All 