Category Archives: Genetic Medicine

Dec. 8, 2019 15:00 UTC

BEDFORD, Mass.--(BUSINESS WIRE)-- Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company pioneering a new way to treat the underlying cause of severe genetic diseases by precisely upregulating protein expression, today presented new preclinical data on STK-001, a potential new disease-modifying medicine for the treatment of Dravet syndrome. Data from studies in non-human primates (NHP) showed STK-001 distributed throughout the brain and achieved target engagement and increased Nav1.1 protein expression throughout the cortex after a single intrathecal injection. Safety findings showed STK-001 to be well-tolerated at the two intrathecal dose levels studied. These data were presented today in a poster session at the American Epilepsy Society (AES) Annual Meeting in Baltimore.

The effects of Dravet syndrome go beyond seizures and often include cognitive regression or developmental stagnation, ataxia, speech impairment and sleep disturbances. The disease is believed to affect multiple areas of the brain, with the cerebral cortex playing a particularly important role, said Edward M. Kaye, M.D., Chief Executive Officer of Stoke Therapeutics. These new data are encouraging because they show the ability of STK-001 to broadly distribute in the brain and to elicit target engagement and increased Nav1.1 throughout the cortex. These results will be included in our planned IND submission and provide additional confidence in our clinical plans for STK-001.

Dravet syndrome is a severe and progressive form of genetic epilepsy that affects approximately 35,000 people in the United States, Canada, Japan, Germany, France and the United Kingdom. Approximately 85% of Dravet syndrome cases are caused by spontaneous, heterozygous mutations in the SCN1A gene, resulting in 50% of normal Nav1.1 protein expression.

Stoke selected two dose levels of STK-001 for this non-GLP study in order to evaluate safety, brain biodistribution, target engagement and Nav1.1 protein expression. On day 1, treatment-nave cynomolgus monkeys were administered a single, bolus intrathecal lumbar (IT-L) injection at one of two dose levels of STK-001. After dosing, the animals underwent standard clinical and neurological observation, and blood samples were collected. STK-001 concentration level, gene expression, and protein expression were assessed in the brain on day 3 and on day 29.

The following are highlights from todays poster presentation.

Stoke plans to submit an investigational new drug (IND) application to the U.S. Food and Drug Administration in early 2020 and, subject to acceptance of the IND, plans to initiate a Phase 1/2 single-ascending dose study in children and adolescents with Dravet syndrome in the first half of 2020.

Details of todays presentation are as follows:

Presentation Title: TANGO Oligonucleotides for the Treatment of Dravet Syndrome: Safety, Biodistribution and Pharmacology in the Non-Human PrimateSession Date & Time: Sunday, December 8, 2019, 10:00 a.m. 4:00 p.m. ETSession Title: Poster Session 2Presenter: Anne Christiansen, Ph.D., Associate Director, Neuroscience, Stoke TherapeuticsPoster Number: 2.195Location: The Baltimore Convention Center, Hall E

Data from preclinical studies of STK-001 in a Dravet syndrome mouse model were presented at AES on Saturday, December 7, 2019. (Poster Number 1.116)

The posters presented at AES are now available online on the Events and Presentations section of Stokes website at https://investor.stoketherapeutics.com/.

About STK-001

STK-001 is an investigational new medicine for the treatment of Dravet syndrome. Stoke believes that STK-001, a proprietary antisense oligonucleotide (ASO), has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome. STK-001 is designed to upregulate NaV1.1 protein expression by leveraging the non-mutant (wild-type) copy of the SCN1A gene to restore physiological NaV1.1 levels, thereby reducing both occurrence of seizures and significant non-seizure comorbidities. Stoke has generated preclinical data demonstrating proof-of-mechanism and proof-of-concept for STK-001. STK-001 has been granted orphan drug designation by the U.S. Food and Drug Administration as a potential new treatment for Dravet syndrome. Stoke plans to submit an investigational new drug (IND) application to the U.S. Food and Drug Administration in early 2020.

About Dravet Syndrome

Dravet syndrome is a severe and progressive genetic epilepsy characterized by frequent, prolonged and refractory seizures, beginning within the first year of life. Dravet syndrome is difficult to treat and has a poor long-term prognosis. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. The effects of the disease go beyond seizures and often include cognitive regression or developmental stagnation, ataxia, speech impairment and sleep disturbances. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP. Dravet syndrome affects approximately 35,000 people in the United States, Canada, Japan, Germany, France and the United Kingdom, and it is not concentrated in a particular geographic area or ethnic group.

About Stoke Therapeutics

Stoke Therapeutics, Inc. (Nasdaq: STOK), is a biotechnology company pioneering a new way to treat the underlying causes of severe genetic diseases by precisely upregulating protein expression to restore target proteins to near normal levels. Stoke aims to develop the first precision medicine platform to target the underlying cause of a broad spectrum of genetic diseases in which the patient has one healthy copy of a gene and one mutated copy that fails to produce a protein essential to health. These diseases, in which loss of approximately 50% of normal protein expression causes disease, are called autosomal dominant haploinsufficiencies. The companys lead investigational new medicine is STK-001, a proprietary antisense oligonucleotide (ASO) that has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome, a severe and progressive genetic epilepsy. Stoke is headquartered in Bedford, Massachusetts with offices in Cambridge, Massachusetts. For more information, visit https://www.stoketherapeutics.com/ or follow the company on Twitter at @StokeTx.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: the ability of STK-001 to improve survival and reduce seizure frequency in mice, as well as its biodistribution, target engagement and ability to increase protein expression in non-human primates; our ability to use study data to advance the development of STK-001; the ability of STK-001 to treat the underlying causes of Dravet syndrome; and the ability of TANGO to design medicines to increase protein production. Statements including words such as plan, continue, expect, or ongoing and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Forward-looking statements are subject to risks and uncertainties that may cause our actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to the companys ability to develop, obtain regulatory approval for and commercialize STK-001 and its future product candidates, the timing and results of preclinical studies and clinical trials, the companys ability to protect intellectual property; and other risks set forth in our filings with the Securities and Exchange Commission, including the risks set forth in our quarterly report on Form 10-Q for the three months ended September 30, 2019. These forward-looking statements speak only as of the date hereof and we specifically disclaim any obligation to update these forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise, except as required by law.

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Stoke Therapeutics Presents Preclinical Data on the Biodistribution, Target Engagement and Safety of STK-001 in Non-Human Primates That Support the...

Dec. 8, 2019 13:00 UTC

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, today announced that it has discovered and validated a novel fetal hemoglobin repressor, Nuclear Factor I X (NFIX), using its gene control platform. The finding sheds light on how the gamma-globin gene, which leads to the production of fetal hemoglobin, is controlled and points to new potential targets for therapeutic intervention in sickle cell disease. These data will be presented in an oral presentation tomorrow at the 61st American Society of Hematology (ASH) Annual Meeting and were highlighted today in an ASH press briefing.

This discovery highlights the power of our platform to elucidate regulatory regions of the genome to control the expression of a single gene for therapeutic benefit, said Eric R. Olson, Ph.D., Syross Chief Scientific Officer. Based on real-world genetic and clinical data from patients, we believe it is possible to provide a functional cure for sickle cell disease by switching on the gamma-globin gene, which is typically turned off at birth, to make healthy red blood cells. Our discovery of NFIX as a critical player in silencing the gamma-globin gene opens up new potential therapeutic approaches as we advance our effort to discover an oral medicine that addresses the root cause of disease in sickle cell patients.

The focus of Syros drug discovery program in sickle cell disease is to develop an oral medicine to mimic a condition found in a subset of patients, who also inherit a hereditary persistence of fetal hemoglobin (HPFH) mutation, in which the gamma-globin gene remains activated after birth. Despite having the mutated adult beta-globin gene that causes sickled cells, these patients are largely asymptomatic because the activated gamma-globin gene leads to the production of enough fetal hemoglobin for red blood cells to function normally.

Using its gene control platform, Syros scientists analyzed and compared regulatory regions of the genome in red blood cell precursors, known as erythroblasts, at various stages of maturity from fetal and adult sources to identify novel drug targets involved in the switch from fetal to adult hemoglobin expression. The genome-wide analysis pointed to NFIX as a potential fetal hemoglobin repressor. The scientists then validated the role of NFIX in silencing fetal hemoglobin by knocking down the NFIX gene in primary cells and an erythroid cell line that expresses adult hemoglobin. The data showed:

The oral presentation will take place tomorrow during the Thalassemia and Globin Gene Regulation: Hemoglobin Regulation and Beta Thalassemia Research session from 4:30-6:30 p.m. ET in Valencia A (W415A) at the Orange County Convention Center, Valencia A (W415A). The ASH presentation is also now available on the Publications and Abstracts section of the Syros website at http://www.syros.com.

About Syros Pharmaceuticals:

Syros is redefining the power of small molecules to control the expression of genes. Based on its unique ability to elucidate regulatory regions of the genome, Syros aims to develop medicines that provide a profound benefit for patients with diseases that have eluded other genomics-based approaches. Syros is advancing a robust pipeline of development candidates, including SY-1425, a first-in-class oral selective RAR agonist in a Phase 2 trial in a genomically defined subset of acute myeloid leukemia patients, and SY-5609, a highly selective and potent oral CDK7 inhibitor in investigational new drug application-enabling studies in cancer. Syros also has multiple preclinical and discovery programs in oncology and monogenic diseases, including sickle cell disease. For more information, visit http://www.syros.com and follow us on Twitter (@SyrosPharma) and LinkedIn.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, including without limitation statements regarding the power of the Companys gene control platform and the Companys ability to discover an oral medicine that can restore healthy blood function in sickle cell patients and provide a functional cure for sickle cell disease. The words anticipate, believe, continue, could, estimate, expect, hope, intend, may, plan, potential, predict, project, target, should, would, and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including Syros ability to: successfully advance the development of its programs; demonstrate in any current and future clinical trials the requisite safety, efficacy and combinability of its drug candidates; replicate scientific and non-clinical data in clinical trials; obtain and maintain patent protection for its drug candidates and the freedom to operate under third party intellectual property; obtain and maintain necessary regulatory approvals; identify, enter into and maintain collaboration agreements with third parties; manage competition; manage expenses; raise the substantial additional capital needed to achieve its business objectives; attract and retain qualified personnel; and successfully execute on its business strategies; risks described under the caption Risk Factors in Syros Annual Report on Form 10-K for the year ended December 31, 2018 and Quarterly Report on Form 10-Q for the quarter ended September 30, 2019, each of which is on file with the Securities and Exchange Commission; and risks described in other filings that Syros makes with the Securities and Exchange Commission in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Syros expressly disclaims any obligation to update any forward-looking statements, whether because of new information, future events or otherwise.

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Syros Presents on Identification of Novel Fetal Hemoglobin Repressor as Part of Broader Drug Discovery Program in Sickle Cell Disease at 61st Annual...

Image from Pixabay.

People in the UK will for the first time have their entire genetic code read from samples taken at a GP practice as part of a pioneering study to assess the potential benefits of screening for gene faults that increase the risk of disease.

Researchers aim to screen the genomes of around a thousand GP patients in London to assess the feasibility of testing for faulty genes that increase the risk of cancer and heart disease, and how acceptable screening is to patients.

The initiative, launched today (Friday), will aim to establish whether whole-genome sequencing in a healthy population can have a significant impact on peoples health by helping diagnose cancer, heart disease and other illnesses much earlier.

The new study is the first in the UK to assess whether whole-genome sequencing can be used to screen for a range of genes linked to disease or response to medicines, and what effect this has on patients healthcare. If successful, it could be a key step towards much more routine use of genetic testing to predict and manage patients future health in the NHS.

The research, called the 90S Study, is led by Professor Ros Eeles, a world-leading expert in cancer genetics at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, and Dr Michael Sandberg, a GP at 90 Sloane Street a private GP practice from which patient volunteers will be recruited.

The study involves further experts from The Institute of Cancer Research (ICR) and The Royal Marsden plus expert cardiologists at Royal Brompton Hospitaland is under the auspices of the 90 Sloane Street Genetic centre, a collaborative team of five consultant geneticists.

The first 20 patients will be evaluated for the psychological effects of genetic screening as part of a study funded by donations to The Institute of Cancer Research (ICR) and through support from the NIHR Biomedical Research Centre at The Royal Marsden and the ICR,and 90 Sloane St.

The study will then be expanded to around a thousand patients initially recruited at 90 Sloane St, with NHS GP practices lined up to join the pilot in a subsequent stage.

There has been huge progress over the last 25 years in identifying inherited causes of disease, such as BRCA gene faults predisposing to breast and ovarian cancer, and Lynch syndrome gene alterations which increase the risk of bowel and uterine cancer. In cardiovascular disease, familial hypercholesterolaemia causes inherited high cholesterol, variants in the long QT genes can cause dangerous heart rhythm disturbances and other gene faults can cause heart muscle disorders.

Advances in the technology to read peoples DNA have made it so much faster and cheaper that it is now practical to screen patients by sequencing their whole genome. There is considerable public interest in genetics, as shown by the growing popularity of unreliable and simplistic direct-to-consumer tests. But until now, there has been no thorough investigation of how properly controlled and validated genomic medicine could be integrated into primary care in the UK.

In the new initiative, researchers will analyse the entire genetic code of people attending a GP surgery and report on around 600 separate genetic changes known to be associated with disease, or in some cases affect how patients respond to or metabolise certain medicines. The study is looking only for actionable gene alterations which if detected would alter choices for an individual such as lifestyle improvements, specific screening and sometimes targeted treatments. It will not report on risk of diseases for which there are no current actions that can be taken.

The study will assess how frequently genetic alterations are picked up by whole-genome sequencing in people with a family history of cancer or heart disease compared with people who do not half of the volunteers will be from each group.

The researchers aim to expand the study to incorporate other partner GP practices and widen the possibility for people to take part. Evidence gathered will inform decision making around the use of whole-genome sequencing in a primary care setting in both the NHS and private practice.

The initiative differs fundamentally from direct-to-consumer testing in that patients will receive genetic screening as part of a detailed medical review. All patients will also have an on-site echocardiogram a heart ultrasound to provide crucial extra information and to reassure those with some genetic risk of heart disease but no signs that this is actually affecting their health.

The project leaders are not suggesting that future population genetic screening would necessarily need to be done with this level of resources and they will be looking for ways of simplifying and improving processes to be suitable for large-volume NHS screening.

Study leader Professor Ros Eeles, Professor of Oncogeneticsat The Institute of Cancer Research, London, and Consultant in Clinical Oncology and Oncogenetics at The Royal Marsden NHS Foundation Trust, said:

Weve seen incredible progress over the last quarter of a century in identifying genetic alterations that are linked to the risk of disease, opening up the possibility to intervene early to improve patients health.

Our new initiative takes cutting-edge science on the genetics of disease into a primary care setting, by sequencing patients entire genomes from samples taken at a GP surgery and testing for the presence of 600 key genetic alterations. What we hope is that genetic screening is practical as a way of picking up genes associated with cancer and heart disease, is psychologically acceptable to patients, and can alter the way they are managed by their GP.

The project will give us crucial information about whether genetic screening in primary care could be feasible, and how we should go about seeking to implement it within the NHS.

Dr Michael Sandberg, General Practitioner at 90 Sloane Street and Co-Principal Investigator for the 90S Study, said:

Genetic information will help us to target and identify high-risk patients, so as to find diseases at an earlier stage and give greater precision to screening and health optimisation in general practice.

Working in partnership with experts at The Institute of Cancer Research and The Royal Marsden means we can integrate whole-genome sequencing into screening in primary care with the genetic support that is essential. There is no doubt that primary care is the future setting for whole-genome screening which will be carried out by specially trained practice nurses supported by GPs and consultant geneticists.

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UK-first study to assess role of whole-genome screening in primary care - The Institute of Cancer Research

Infertility was always a very serious problem for society, both as a medical and as a social-demographic issue. In an era of late parenting, combined with career growth goals which weakened the institution of family, the hazardous effects of toxic influences of ecology and environmental factors saw infertility becoming not just a personal tragedy but a global problem.

Innova Invitro, established and guided by Dr. Ketevan Osidze who is well-known for as being a doctor with excellent results, is fully dedicated to meeting patients expectations. The clinic has been operating since 2016 and is recognized worldwide as having international standards and high pregnancy rates.

We all know that to be a leading clinic in Tbilisi requires hard work. Please tell us a little more about Innova Invitro.

I am really happy to have such an amazing team. I have 16 years working experience in the field of IVF but my goal was to start with the best possible embryology lab. I chose one of the leaders in the field of IVI, the Valencia Institute of Infertility, as a provider of accreditation and runner of our embryology service. Our Embryology Lab Director Jordan Garcia Ortega is a well-known professional worldwide with amazing experience. I think having such an influential person here had an overall impact on the service and quality in this region. We are proud that several Georgians have been trained by him. We continue to employee embryologists from IVI as the number of patients is growing constantly.

What is main activity of your clinic?

We offer services of any difficulty as we are fully equipped and have the know-how. To performing IVF and ICSI intracytoplasmic sperm injection, we can add genetic tests of embryos PGT-A, PGD, and NIPD tests for pregnancies. Our main activity includes ambulatory treatment and diagnostics of infertility. The clinic has all the necessary means to treat women and men: an external control hormonal lab, referral department of laparoscopy, endocrinology and andrology services, and outstanding specialists with up to date ultrasound and XR machines. We think that only proper diagnosis can ensure a successful medical intervention. Our multidiscipline team of gynaecologists, obstetricians, endocrinologists, therapeutics, and anaesthesiologists care about the well-being and satisfaction of patients and their babies.

We feel special responsibility providing donation and surrogacy services, as it is not only medical intervention. We care very much about the transparency and safety of the process for all parties couples, egg or sperm donors and surrogate mothers. This is an absolutely legal process which is well controlled by the government.

We know that you have very positive feedback from patients. What makes your clinic different from others?

Our priority is high standards of medical service, and an individualized and timely approach to any case with properly planned interventions. We have a special department for international patients to make it easy for them to plan and prepare for surrogacy and donation services. They arrive only at the final stages for the procedure and have to spend only several days in Tbilisi. I have to mention that they usually want to stay longer just as tourists and usually come back for several weeks with friends after the babies are born. I can say that medical tourism is contributing a lot to the rise of tourism activity overall. Timely and planned visits and long-distance services are very important to local customers as well, as a lack of time is a reality for many.

What is main diagnosis of your patients?

It is most commonly infertility due to tubal patency problems post-inflammation or post-surgery. Everyone is concerned about the very fast decline in sperm parameters and subfertility and infertility. Along with genetic errors in the Y chromosome, this situation is connected with ecology, air pollution, chemicals in food, steroid abuse and heavy metals in building materials, possible the harm of Wi-Fi and other urban factors, including stress. We are really glad to see men overcoming the stigma of coming for a check-up and visiting earlier, sometimes even before marriage. Infertility is problem of a couple not of a single individual, so faster diagnosis gives faster results.

What are your plans?

We follow all the advances in reproductive medicine field. We would like to share our experience and expertise with professional society by participating in international research and training programs. As part of social responsibility, we will continue to make efforts to make society more informed and educated about infertility treatment and prevention.

What does partnering with IVI mean for your clinic and what is the priority area of activity for Inova Invitro?

The priority area for Inova Invitro is the comprehensive diagnosis and management of all pathologies of infertility, all the while adhering to international standards pertaining to the treatment procedures. The main focus is on vitro fertilization and donation-surrogacy programs. We are home to personnel of the highest calibre with 15 years working experience in the realm of in vitro fertilization. The collaboration with IVI gives our specialists the opportunity to, along with providing the best standards of treatment, develop an integrated approach that incorporates complex diagnostics and consultation.

What makes patients turn to donation or surrogacy? What do these two procedures entail?

Premature ovarian syndrome, genetic abnormalities, poor quality eggs or embryos are among the conditions that urge us to recommend egg donation. Egg fertilization is carried out in the embryological laboratory by the recipient's partner or donor sperm, then transplanted into the uterine cavity of a "potential mother" under ultrasonography. About 12 days after embryo transfer, a pregnancy test or blood test is performed to determine pregnancy.

In case of infertility, when referring to the surrogacy program, stimulation is provided for the biological mother or the donor, and the fertilized egg is transferred to the surrogate mothers womb. Surrogate mothers have no genetic relationship with the embryos.

What are the root causes of infertility?

Infertility is a sensitive global issue. The causes may range from stress, late marriage, ecology, or the deterioration of male spermogram, among others. Quite often, a delayed visit to a doctor becomes one of the major obstacles.

What do you see as the major priority of Inova Invitro?

Our collaboration with Spain, an indisputable leader in the field, and working in accordance with the standards that they set, has been Invitros major asset. Partnering with IVI is a major advantage in terms of research, results and technical support.

Inova Invitro is a clinic that never fails to adhere to the best of European standards, which is also stressed by its maintenance of an embryological laboratory, headed by Jordan Garcia Ortega, a leading specialist at IVI.

How does your team work towards the clinics common goal?

The success of Inova Invitro almost entirely lies in our team's passion and effort to deliver the latest in state-of-the-art expertise and innovation. IVI specialists are valuable members of our team. Our clinic is home for specialists from all the adjacent fields to fertilization, which is another remarkable asset. One can benefit from all the services he/she needs in the comfort of a single space.

What is the pace of development for the field of reproductive medicine?

The field is developing rapidly; new methods are emerging, such as the so-called "gene modification" or embryonic genetic evaluation. All new discoveries are accessible at our clinic and we apply them strictly in accordance with healthcare licensing.

The field of reproductive medicine is undergoing some outstanding developments in Georgia, as the country's healthcare system actively supports it. Under our state-controlled regulations, the patient receives a safe and comprehensive service within a high quality program. The rights of patients, donors and surrogates (with whom the clinic works in close cooperation) are maximally protected.

Tell us about the improving trends of late.

The newly emerging trend is that an ever-increasing number of men address our clinic.

Even before marriage, the couples conduct research and check on their health. Egg and embryo freezing methods are also becoming popular- all these are vital turning points!

What are your last thoughts or advice for patients?

This century has brought to light that the ecological situation and a stressful backdrop work against us. Even with Wi-Fi, the spermogram concentration is weakened and the indicators are corrupted.

Consequently, there are many things to consider in terms of pregnancy. Timely referral to a doctor will prevent many problems.

09 December 2019 17:47

More:
Innova Invitro The Place Where Parenting Dreams Come True - Georgia Today

Astellas Pharma Inc. said Tuesday that it will buy U.S. genetic medicine developer Audentes Therapeutics Inc. for some $3 billion.

The Japanese company hopes to complete the acquisition of the San Francisco-based company through a tender offer by the end of March next year.

Astellas aims to nurture the genetic medicine business as a new pillar of growth by purchasing Audentes, which develops remedies mainly for serious and rare neuromuscular diseases that stem from genetic defects and can lead to substantial losses of muscle strength, respiratory failure and early death.

By using its own international business base and Audentes knowledge, Astellas can accelerate the development speed of genetic medicine, the Japanese company said.

Established in 2012, Audentes has some 270 employees. Its stock is listed on the U.S. Nasdaq market.

It plans to file applications for approval of drugs for neuromuscular diseases in the United States and Europe next year.

Read the original here:
Astellas to buy US genetic medicine developer Audentes for $3 billion - The Japan Times

As these clinical tests became more common, scientists were also busy trying to drill deeper into the substance of DNA, the chemical structure of which had only been deciphered in 1953 by James Watson, Francis Crick, and Rosalind Franklin. Over the next few decades, scientists would come to understand that its helix-shaped pattern of paired basesadenine, thymine, cytosine, and guaninefunctioned like letters, spelling out words that a cell would decode into amino acids, the building blocks of proteins. They would also begin to realize that most of the human genomeabout 98 percentdoesnt actually code for proteins. In the '70s, junk DNA became the popularized term for these nonfunctional sections.

Not long after, in 1984, a British geneticist named Alec Jeffreys stumbled upon a use for all that so-called junk DNA: crime-fighting. In these regions of the genome, the DNA molecule tends to duplicate itself, like its stuttering over the same word over and over again. Scientists can capture and count these stutters, known as short tandem repeats. And because the number of STRs a person has at various locations is unique to them, they can be used to build a personally identifiable profile, or DNA fingerprint.

Genetic Testing Glossary

GenotypingTesting technology, often chip-based, that generates a partial list of your unique genetic differences.

Whole-genome sequencingA method used to determine the exact sequence of your entire genome, all 6.4 billion letters.

Whole-exome sequencingA method used to determine the exact sequence of the protein-coding portion of your genome, comprising about 22,000 genes.

Coverage/DepthA measure of how many times a DNA sequence has been proofread. 30X average depth of coverage is the benchmark of a high-quality sequence.

VariantA generic term referring to places in someones genome that differ from a reference genome

Single Nucleotide Polymorphism (SNP)A variant defined by a single letter change

Polygenic Score (PGS)An algorithm that adds up the effects of multiple variants to predict the likelihood of a physical or behavioral trait based on your DNA.

Preimplantation Genetic Diagnosis (PGD)A method for testing IVF embryos for genetic defects prior to starting a pregnancy.

Non-Invasive Prenatal TestingA method for screening a fetus for certain genetic disorders by testing the mothers blood. Confirming a diagnosis requires more invasive procedures.

Carrier ScreenA test used to find out if you carry any genes for disorders that you could pass on to your children.

Short Tandem Repeat (STR)A pattern of repeating sequences in the noncoding part of your genome used in forensic DNA testing

CODISA national database of genetic profiles collected from criminals and crime scenes, maintained by the US government.

In 1987, this technique was used for the first time in a police investigation, leading to the arrest and conviction of Colin Pitchfork for the rape and murder of two young women in the UK. That same year, Tommie Lee Andrews, who raped and stabbed to death a woman in Florida, became the first person in the US to be convicted as a result of DNA evidence. Since then, forensic DNA testing has put millions of criminals behind bars. In 1994, Congress signed the DNA Identification Act, giving the US Federal Bureau of Investigation authority to maintain a national database of genetic profiles collected from criminal offenders. As of September 2019, this database, known as CODIS, contains DNA from nearly 14 million people convicted of crimes, as well as 3.7 million arrestees, and 973,000 samples gathered at crime scenes.

Throughout the '80s and '90s, while cops were rushing to use DNA to catch rapists and murderers, geneticists were slowly doing detective work of their own. By linking health records, family pedigrees, disease registries, and STR locations and lengths, scientific sleuths painstakingly began to map traits onto chromosomes, eventually identifying the genes responsible for a number of inherited conditions, including Huntingtons disease, cystic fibrosis, and sickle-cell anemia. These diseases linked to single genes, so-called monogenic conditions, are basically binaryif you have the genetic mutation youre almost certain to develop the disease. And once the sequences for these faulty genes were revealed, it wasnt too hard to test for their presence. All you had to do was design a probea single strand of DNA attached to a signal molecule, that would send out a fluorescent burst or some other chemical flare when it found its matching sequence.

As the new millennium approached, companies were beginning to pilot such tests in various clinical settings, i.e. with a doctors order. That included testing amniotic fluid as part of prenatal screening, testing the blood of prospective parents (whats known as carrier screening), and testing the cells of embryos created by in vitro fertilization, in a process called pre-implantation diagnosis. These tests were expensive and targeted only at people with family histories of so-called monogenic diseases. Developing tests to assess a healthy persons risk of developing more complex conditions caused by the interaction of multiple genesthings like heart disease, diabetes, and cancerwould require a more detailed map of human DNA than the fragmented picture scientists had so far decoded. Luckily, that was just around the corner.

In 2000, a rough draft of the human genome sequence was made freely available online, followed three years later by a more complete, high-resolution version. With it, scientists and engineers now had enough information to load up chips with not one or two DNA probes but thousands, even hundreds of thousands. These microarrays made it possible to simultaneously scan a persons genome for thousands of SNPs, or single nucleotide polymorphismssingle changes in the arrangement of DNA letters that make people unique. These SNPs, or variants as theyre alternatively known, can be tallied up to rank a persons susceptibility to various illnesses.

And because this SNP snapshot technology, known as genotyping, could be done much cheaper than full sequencingin 2006 it cost $1,000 as opposed to $1 million for a full-genome scanit launched not only a new wave of research but a new industry: direct-to-consumer DNA testing.

Starting in the mid-2000s, dozens of companies began selling people a new genetic experience that didnt have to take place in a doctors office. They would take a sample of your DNAa few laboriously salivated milliliters of drool sent through the mailscan it, and peer into your ancestral past as well as forecast your genetic future. In the early days, these tests could provide only a limited amount of information. And many companies went under while waiting for researchers to amass more knowledge about the links between certain genes and human traits. But one deep-pocketed Silicon Valley startup weathered the creeping adoption curve (and a spat with the US Food and Drug Administration) to become synonymous with the retail genomics business: 23andMe.

Today though, as costs sink even further and the internet makes the exchange of cheek cells for genetic insights virtually frictionless, 23andMe again has plenty of competition. A recent study identified nearly 250 companies offering DNA tests that people can buy online. Most of these are tests for disease predisposition, ancestry, and paternity. But others offer biological inheritance as infotainmenttests offering matchmaking services, predicting childrens talents, recommending the right diet, or even identifying wines you might be genetically inclined to enjoy.

Customers should be aware though, that many of these recreational tests offer results with little relationship to realitythe science is still just too premature to be truly predictive for most complicated traits. They might be fun, but dont take them too seriously. (And if you care about genetic privacy, dont take them at all!) Even the more medically focused tests, like 23andMes health reports, should be taken with a grain of salt. Its testing formula for breast cancer risk, for example, is built around just three genetic variants in the BRCA genes, common in Ashkenazi Jewish populations and known to be associated with cancer. But there are thousands of other variants in those genes that can also raise your risk of breast cancer. Its just that 23andMes DNA chip isnt set up to capture them. In other words, a clean bill of health from 23andMe shouldnt be taken as definitive. The company emphasizes that its tests are probability readings, theyre not meant to be diagnostic. So if anything does come up, you still have to go see a doctor for confirmatory clinical testing.

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What Is Genetic Testing? The Complete WIRED Guide - WIRED