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Genetic Medicine | Department of Medicine

Advances in molecular biology and human genetics, coupled with the completion of the Human Genome Project and the increasing power of quantitative genetics to identify disease susceptibility genes, are contributing to a revolution in the practice of medicine. In the 21st century, practicing physicians will focus more on defining genetically determined disease susceptibility in individual patients. This strategy will be used to prevent, modify, and treat a wide array of common disorders that have unique heritable risk factors such as hypertension, obesity, diabetes, arthrosclerosis, and cancer.

The Division of Genetic Medicine provides an academic environment enabling researchers to explore new relationships between disease susceptibility and human genetics. The Division of Genetic Medicine was established to host both research and clinical research programs focused on the genetic basis of health and disease. Equipped with state-of-the-art research tools and facilities, our faculty members are advancing knowledge of the common genetic determinants of cancer, congenital neuropathies, and heart disease. The Division faculty work jointly with the Vanderbilt-Ingram Cancer Center to support the Hereditary Cancer Clinic for treating patients and families who have an inherited predisposition to various malignancies.

Genetic differences in humans at the molecular level not only contribute to the disease process but also significantly impact an individuals ability to respond optimally to drug therapy. Vanderbilt is a pioneer in precisely identifying genetic differences between patients and making rational treatment decisions at the bedside.

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Genetic Medicine | Department of Medicine

Medical genetics – Wikipedia

Medical genetics is the branch of medicine that involves the diagnosis and management of hereditary disorders. Medical genetics differs from human genetics in that human genetics is a field of scientific research that may or may not apply to medicine, while medical genetics refers to the application of genetics to medical care. For example, research on the causes and inheritance of genetic disorders would be considered within both human genetics and medical genetics, while the diagnosis, management, and counselling people with genetic disorders would be considered part of medical genetics.

In contrast, the study of typically non-medical phenotypes such as the genetics of eye color would be considered part of human genetics, but not necessarily relevant to medical genetics (except in situations such as albinism). Genetic medicine is a newer term for medical genetics and incorporates areas such as gene therapy, personalized medicine, and the rapidly emerging new medical specialty, predictive medicine.

Medical genetics encompasses many different areas, including clinical practice of physicians, genetic counselors, and nutritionists, clinical diagnostic laboratory activities, and research into the causes and inheritance of genetic disorders. Examples of conditions that fall within the scope of medical genetics include birth defects and dysmorphology, mental retardation, autism, mitochondrial disorders, skeletal dysplasia, connective tissue disorders, cancer genetics, teratogens, and prenatal diagnosis. Medical genetics is increasingly becoming relevant to many common diseases. Overlaps with other medical specialties are beginning to emerge, as recent advances in genetics are revealing etiologies for neurologic, endocrine, cardiovascular, pulmonary, ophthalmologic, renal, psychiatric, and dermatologic conditions. The medical genetics community is increasingly involved with individuals who have undertaken elective genetic and genomic testing.

In some ways, many of the individual fields within medical genetics are hybrids between clinical care and research. This is due in part to recent advances in science and technology (for example, see the Human genome project) that have enabled an unprecedented understanding of genetic disorders.

Clinical genetics is the practice of clinical medicine with particular attention to hereditary disorders. Referrals are made to genetics clinics for a variety of reasons, including birth defects, developmental delay, autism, epilepsy, short stature, and many others. Examples of genetic syndromes that are commonly seen in the genetics clinic include chromosomal rearrangements, Down syndrome, DiGeorge syndrome (22q11.2 Deletion Syndrome), Fragile X syndrome, Marfan syndrome, Neurofibromatosis, Turner syndrome, and Williams syndrome.

In the United States, Doctors who practice clinical genetics are accredited by the American Board of Medical Genetics and Genomics (ABMGG).[1] In order to become a board-certified practitioner of Clinical Genetics, a physician must complete a minimum of 24 months of training in a program accredited by the ABMGG. Individuals seeking acceptance into clinical genetics training programs must hold an M.D. or D.O. degree (or their equivalent) and have completed a minimum of 24 months of training in an ACGME-accredited residency program in internal medicine, pediatrics, obstetrics and gynecology, or other medical specialty.[2]

Metabolic (or biochemical) genetics involves the diagnosis and management of inborn errors of metabolism in which patients have enzymatic deficiencies that perturb biochemical pathways involved in metabolism of carbohydrates, amino acids, and lipids. Examples of metabolic disorders include galactosemia, glycogen storage disease, lysosomal storage disorders, metabolic acidosis, peroxisomal disorders, phenylketonuria, and urea cycle disorders.

Cytogenetics is the study of chromosomes and chromosome abnormalities. While cytogenetics historically relied on microscopy to analyze chromosomes, new molecular technologies such as array comparative genomic hybridization are now becoming widely used. Examples of chromosome abnormalities include aneuploidy, chromosomal rearrangements, and genomic deletion/duplication disorders.

Molecular genetics involves the discovery of and laboratory testing for DNA mutations that underlie many single gene disorders. Examples of single gene disorders include achondroplasia, cystic fibrosis, Duchenne muscular dystrophy, hereditary breast cancer (BRCA1/2), Huntington disease, Marfan syndrome, Noonan syndrome, and Rett syndrome. Molecular tests are also used in the diagnosis of syndromes involving epigenetic abnormalities, such as Angelman syndrome, Beckwith-Wiedemann syndrome, Prader-willi syndrome, and uniparental disomy.

Mitochondrial genetics concerns the diagnosis and management of mitochondrial disorders, which have a molecular basis but often result in biochemical abnormalities due to deficient energy production.

There exists some overlap between medical genetic diagnostic laboratories and molecular pathology.

Genetic counseling is the process of providing information about genetic conditions, diagnostic testing, and risks in other family members, within the framework of nondirective counseling. Genetic counselors are non-physician members of the medical genetics team who specialize in family risk assessment and counseling of patients regarding genetic disorders. The precise role of the genetic counselor varies somewhat depending on the disorder.When working alongside geneticists, genetic counselors normally specialize in pediatric genetics which focuses on developmental abnormalities present in newborns, infants or children. The major goal of pediatric counseling is attempting to explain the genetic basis behind the child's developmental concerns in a compassionate and articulated manner that allows the potentially distressed or frustrated parents to easily understand the information. As well, genetic counselors normally take a family pedigree, which summarizes the medical history of the patient's family. This then aids the clinical geneticist in the differential diagnosis process and help determine which further steps should be taken to help the patient. [3]

Although genetics has its roots back in the 19th century with the work of the Bohemian monk Gregor Mendel and other pioneering scientists, human genetics emerged later. It started to develop, albeit slowly, during the first half of the 20th century. Mendelian (single-gene) inheritance was studied in a number of important disorders such as albinism, brachydactyly (short fingers and toes), and hemophilia. Mathematical approaches were also devised and applied to human genetics. Population genetics was created.

Medical genetics was a late developer, emerging largely after the close of World War II (1945) when the eugenics movement had fallen into disrepute. The Nazi misuse of eugenics sounded its death knell. Shorn of eugenics, a scientific approach could be used and was applied to human and medical genetics. Medical genetics saw an increasingly rapid rise in the second half of the 20th century and continues in the 21st century.

The clinical setting in which patients are evaluated determines the scope of practice, diagnostic, and therapeutic interventions. For the purposes of general discussion, the typical encounters between patients and genetic practitioners may involve:

Each patient will undergo a diagnostic evaluation tailored to their own particular presenting signs and symptoms. The geneticist will establish a differential diagnosis and recommend appropriate testing. These tests might evaluate for chromosomal disorders, inborn errors of metabolism, or single gene disorders.

Chromosome studies are used in the general genetics clinic to determine a cause for developmental delay/mental retardation, birth defects, dysmorphic features, and/or autism. Chromosome analysis is also performed in the prenatal setting to determine whether a fetus is affected with aneuploidy or other chromosome rearrangements. Finally, chromosome abnormalities are often detected in cancer samples. A large number of different methods have been developed for chromosome analysis:

Biochemical studies are performed to screen for imbalances of metabolites in the bodily fluid, usually the blood (plasma/serum) or urine, but also in cerebrospinal fluid (CSF). Specific tests of enzyme function (either in leukocytes, skin fibroblasts, liver, or muscle) are also employed under certain circumstances. In the US, the newborn screen incorporates biochemical tests to screen for treatable conditions such as galactosemia and phenylketonuria (PKU). Patients suspected to have a metabolic condition might undergo the following tests:

Each cell of the body contains the hereditary information (DNA) wrapped up in structures called chromosomes. Since genetic syndromes are typically the result of alterations of the chromosomes or genes, there is no treatment currently available that can correct the genetic alterations in every cell of the body. Therefore, there is currently no "cure" for genetic disorders. However, for many genetic syndromes there is treatment available to manage the symptoms. In some cases, particularly inborn errors of metabolism, the mechanism of disease is well understood and offers the potential for dietary and medical management to prevent or reduce the long-term complications. In other cases, infusion therapy is used to replace the missing enzyme. Current research is actively seeking to use gene therapy or other new medications to treat specific genetic disorders.

In general, metabolic disorders arise from enzyme deficiencies that disrupt normal metabolic pathways. For instance, in the hypothetical example:

Compound "A" is metabolized to "B" by enzyme "X", compound "B" is metabolized to "C" by enzyme "Y", and compound "C" is metabolized to "D" by enzyme "Z".If enzyme "Z" is missing, compound "D" will be missing, while compounds "A", "B", and "C" will build up. The pathogenesis of this particular condition could result from lack of compound "D", if it is critical for some cellular function, or from toxicity due to excess "A", "B", and/or "C", or from toxicity due to the excess of "E" which is normally only present in small amounts and only accumulates when "C" is in excess. Treatment of the metabolic disorder could be achieved through dietary supplementation of compound "D" and dietary restriction of compounds "A", "B", and/or "C" or by treatment with a medication that promoted disposal of excess "A", "B", "C" or "E". Another approach that can be taken is enzyme replacement therapy, in which a patient is given an infusion of the missing enzyme "Z" or cofactor therapy to increase the efficacy of any residual "Z" activity.

Dietary restriction and supplementation are key measures taken in several well-known metabolic disorders, including galactosemia, phenylketonuria (PKU), maple syrup urine disease, organic acidurias and urea cycle disorders. Such restrictive diets can be difficult for the patient and family to maintain, and require close consultation with a nutritionist who has special experience in metabolic disorders. The composition of the diet will change depending on the caloric needs of the growing child and special attention is needed during a pregnancy if a woman is affected with one of these disorders.

Medical approaches include enhancement of residual enzyme activity (in cases where the enzyme is made but is not functioning properly), inhibition of other enzymes in the biochemical pathway to prevent buildup of a toxic compound, or diversion of a toxic compound to another form that can be excreted. Examples include the use of high doses of pyridoxine (vitamin B6) in some patients with homocystinuria to boost the activity of the residual cystathione synthase enzyme, administration of biotin to restore activity of several enzymes affected by deficiency of biotinidase, treatment with NTBC in Tyrosinemia to inhibit the production of succinylacetone which causes liver toxicity, and the use of sodium benzoate to decrease ammonia build-up in urea cycle disorders.

Certain lysosomal storage diseases are treated with infusions of a recombinant enzyme (produced in a laboratory), which can reduce the accumulation of the compounds in various tissues. Examples include Gaucher disease, Fabry disease, Mucopolysaccharidoses and Glycogen storage disease type II. Such treatments are limited by the ability of the enzyme to reach the affected areas (the blood brain barrier prevents enzyme from reaching the brain, for example), and can sometimes be associated with allergic reactions. The long-term clinical effectiveness of enzyme replacement therapies vary widely among different disorders.

There are a variety of career paths within the field of medical genetics, and naturally the training required for each area differs considerably. The information included in this section applies to the typical pathways in the United States and there may be differences in other countries. US practitioners in clinical, counseling, or diagnostic subspecialties generally obtain board certification through the American Board of Medical Genetics.

Genetic information provides a unique type of knowledge about an individual and his/her family, fundamentally different from a typically laboratory test that provides a "snapshot" of an individual's health status. The unique status of genetic information and inherited disease has a number of ramifications with regard to ethical, legal, and societal concerns.

On 19 March 2015, scientists urged a worldwide ban on clinical use of methods, particularly the use of CRISPR and zinc finger, to edit the human genome in a way that can be inherited.[4][5][6][7] In April 2015 and April 2016, Chinese researchers reported results of basic research to edit the DNA of non-viable human embryos using CRISPR.[8][9][10] In February 2016, British scientists were given permission by regulators to genetically modify human embryos by using CRISPR and related techniques on condition that the embryos were destroyed within seven days.[11] In June 2016 the Dutch government was reported to be planning to follow suit with similar regulations which would specify a 14-day limit.[12]

The more empirical approach to human and medical genetics was formalized by the founding in 1948 of the American Society of Human Genetics. The Society first began annual meetings that year (1948) and its international counterpart, the International Congress of Human Genetics, has met every 5 years since its inception in 1956. The Society publishes the American Journal of Human Genetics on a monthly basis.

Medical genetics is now recognized as a distinct medical specialty in the U.S. with its own approved board (the American Board of Medical Genetics) and clinical specialty college (the American College of Medical Genetics). The College holds an annual scientific meeting, publishes a monthly journal, Genetics in Medicine, and issues position papers and clinical practice guidelines on a variety of topics relevant to human genetics.

The broad range of research in medical genetics reflects the overall scope of this field, including basic research on genetic inheritance and the human genome, mechanisms of genetic and metabolic disorders, translational research on new treatment modalities, and the impact of genetic testing

Basic research geneticists usually undertake research in universities, biotechnology firms and research institutes.

Sometimes the link between a disease and an unusual gene variant is more subtle. The genetic architecture of common diseases is an important factor in determining the extent to which patterns of genetic variation influence group differences in health outcomes.[13][14][15] According to the common disease/common variant hypothesis, common variants present in the ancestral population before the dispersal of modern humans from Africa play an important role in human diseases.[16] Genetic variants associated with Alzheimer disease, deep venous thrombosis, Crohn disease, and type 2 diabetes appear to adhere to this model.[17] However, the generality of the model has not yet been established and, in some cases, is in doubt.[14][18][19] Some diseases, such as many common cancers, appear not to be well described by the common disease/common variant model.[20]

Another possibility is that common diseases arise in part through the action of combinations of variants that are individually rare.[21][22] Most of the disease-associated alleles discovered to date have been rare, and rare variants are more likely than common variants to be differentially distributed among groups distinguished by ancestry.[20][23] However, groups could harbor different, though perhaps overlapping, sets of rare variants, which would reduce contrasts between groups in the incidence of the disease.

The number of variants contributing to a disease and the interactions among those variants also could influence the distribution of diseases among groups. The difficulty that has been encountered in finding contributory alleles for complex diseases and in replicating positive associations suggests that many complex diseases involve numerous variants rather than a moderate number of alleles, and the influence of any given variant may depend in critical ways on the genetic and environmental background.[18][24][25][26] If many alleles are required to increase susceptibility to a disease, the odds are low that the necessary combination of alleles would become concentrated in a particular group purely through drift.[27]

One area in which population categories can be important considerations in genetics research is in controlling for confounding between population substructure, environmental exposures, and health outcomes. Association studies can produce spurious results if cases and controls have differing allele frequencies for genes that are not related to the disease being studied,[28] although the magnitude of this problem in genetic association studies is subject to debate.[29][30] Various methods have been developed to detect and account for population substructure,[31][32] but these methods can be difficult to apply in practice.[33]

Population substructure also can be used to advantage in genetic association studies. For example, populations that represent recent mixtures of geographically separated ancestral groups can exhibit longer-range linkage disequilibrium between susceptibility alleles and genetic markers than is the case for other populations.[34][35][36][37] Genetic studies can use this admixture linkage disequilibrium to search for disease alleles with fewer markers than would be needed otherwise. Association studies also can take advantage of the contrasting experiences of racial or ethnic groups, including migrant groups, to search for interactions between particular alleles and environmental factors that might influence health.[38][39]

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Medical genetics - Wikipedia

Distribution of Genes Encoding Virulence Factors and the Genetic Diver | IDR – Dove Medical Press

Ahmad Farajzadeh-Sheikh, 1, 2 Mohammad Savari, 1, 2 Khadijeh Ahmadi, 2, 3 Hossein Hosseini Nave, 4 Mojtaba Shahin, 5 Maryam Afzali 2

1Department of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 2Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 3Abadan Faculty of Medical Sciences, Abadan, Iran; 4Department of Microbiology and Virology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran; 5Department of Medical Laboratory Sciences, Faculty of Medical Sciences, Islamic Azad University, Arak, Iran

Correspondence: Maryam AfzaliDepartment of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Golestan Blvd 39345-61355, Ahvaz, IranTel +09156127753Fax +98-61-3333 2036Email afzalimaryam@ymail.com

Background: Entero-invasive E. coli (EIEC) is one of the causes of bacillary dysentery in adults and children. The ability of EIEC to invade and colonize the surface of epithelial cells is influenced by many virulence factors. This study aimed to investigate the distribution of virulence factor genes in EIEC strains isolated from patients with diarrhea in Ahvaz, Iran, as well as the genetic diversity between these isolates by Multilocus variable-number tandem repeat analysis (MLVA).Materials and Methods: A total of 581 diarrheic stool samples were collected from patients with diarrhea attending two hospitals, in Ahvaz, Iran. The E. coli strains were identified by biochemical methods. Subsequently, all E. coli isolates were identified as EIEC by polymerase chain reaction (PCR) for the ipaH gene. The EIEC isolates evaluated by PCR for the presence of 8 virulence genes (ial, sen, virF, invE, sat, sigA, pic, and sepA). All EIEC strains were genotyped by the MLVA typing method.Results: A total of 13 EIEC isolates were identified. The presence of ial, virF, invE, sen, sigA, pic, and sat genes was confirmed among 92.3%, 84.6%, 84.6%, 76.9%, 69.2%, and 15.3% of EIEC isolates, respectively. On the other hand, none of the isolates were positive for the sepA gene. The EIEC isolates were divided into 11 MLVA types.Conclusion: Our results showed a high distribution of virulence genes among EIEC isolates in our region. This study showed that MLVA is a promising typing technique for epidemiological studies. MLVA can supply data in the form of codes that can be saved in the database and easily shared among laboratories, research institutes, and even hospitals.

Keywords: entero-invasive Escherichia coli, diarrhea, virulence factor, MLVA

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

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In defence of imprecise medicine: the benefits of routine treatments for common diseases – The Conversation UK

The NHS states that it will be the world-leading healthcare system in its use of cutting-edge genomic technologies to predict and diagnose inherited and acquired disease, and to personalise treatments and interventions. As all diseases are either inherited or acquired, this is no modest claim.

This approach to medical care is known as precision medicine, and given the hype that surrounds the model, you might be forgiven for thinking that the usual practice of imprecise medicine is greatly inferior. And yet it has been the routine and, in many respects, indiscriminate use of effective treatments for a range of common diseases that has improved the health of large numbers of patients over the past few decades.

Precision medicine assumes that genes play a big role in causing diseases and that new treatments targeting genes and their processes can have significant benefits. The government is so enthusiastic about this new approach that in 2019 it offered gene sequencing to the entire UK population, albeit for a fee. In announcing this initiative, Health Secretary Matt Hancock said there are huge benefits to sequencing as many genomes as we can every genome sequenced moves us a step closer to unlocking life-saving treatments.

But just how big are the benefits likely to be? How relevant is precision medicine to preventing and treating the diseases responsible for most premature deaths and hospital admissions in the UK, such as heart disease, stroke, hip fracture and dementia diseases where genetic links are not clear.

In a study of half a million participants in the UK Biobank project, 1.7 million separate gene variants were shown to be associated with heart disease. Yet in combination, these variants accounted for less than 3% of heart disease after considering known causes such as smoking and high cholesterol.

Precision medicine seems likely to offer most promise for preventing and treating less common diseases, as they are more likely to have a major genetic cause. The poster child for precision medicine is the drug trastuzumab (also known as Herceptin), which was developed following the discovery of HER2, a genetic factor implicated in about 20% of breast cancer cases.

Trastuzumab targets a specific biological mechanism that is involved in HER2 positive cancer, and treatment with this drug improves survival and reduces cancer recurrence. But the effects are not quite as remarkable as has been sometimes suggested. A meta-analysis of clinical trials reported that after ten years, 74% of patients treated with trastuzumab remained alive and recurrence-free compared with 62% of those who did not receive trastuzumab. A worthwhile effect for sure, but only for about 10-15% of patients.

Comparing these important but small gains with the impact of an imprecise approach taken to other diseases offers a stark contrast. For example, HIV used to be a death sentence. Today, 94% of people with the disease are still alive after 30 years, thanks to antiretroviral drugs. Similarly, deaths in the five-year period following a heart attack declined by 70% between 1979 and 2013, largely due to the routine use of drugs such as aspirin, ACE inhibitors and statins.

Interestingly, for both heart attacks and HIV, when efforts have been made to personalise treatment, it has generally led to worse outcomes; in large part as a consequence of doctors withholding treatments they believe may not be beneficial or could be dangerous for a particular person. Unfortunately, such clinical insights are more often wrong than right.

Its hard not to conclude that the nations health would be better served by the NHS if it aspired to be a global leader in the standardisation of care for common serious diseases. Lets not let the current enthusiasm for precision medicine blind us to the benefits of the imprecise medicine we know saves millions of lives every year.

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In defence of imprecise medicine: the benefits of routine treatments for common diseases - The Conversation UK

IDEAYA Biosciences and Boston Children’s Hospital Collaborate on Preclinical Evaluation of IDE196 for Sturge Weber Syndrome – a Rare Disease…

SOUTH SAN FRANCISCO, Calif., Jan. 10, 2020 /PRNewswire/ -- IDEAYA Biosciences, Inc. (NASDAQ:IDYA), an oncology-focused precision medicine company committed to the discovery and development of targeted therapeutics, announced that the company has entered into a Sponsored Research Agreement with Boston Children's Hospital for preclinical evaluation of the role of protein kinase C (PKC) in Sturge Weber syndrome (SWS), a rare neurocutaneous disorder characterized by capillary malformations and associated with mutations in GNAQ.

Under the agreement, IDEAYA will collaborate with and support research at Boston Children's Hospital in the laboratory of Dr. Joyce Bischoff, Ph.D., Research Associate, Department of Surgery and Professor, Harvard Medical School, who is Principal Investigator of the research studies. The preclinical research will evaluate IDE196, a potent, selective PKC inhibitor, in vitro to assess whether pharmacological inhibition of PKC in endothelial cells having GNAQ mutations will restore normal cell function, as well as in vivo to assess whether pharmacological inhibition of PKC can regulate blood vessel size in murine models that recapitulate enlarged vessels seen in SWS capillary malformations.

SWS is a rare disease characterized by a facial birthmark, neurological abnormalities (e.g. seizures) and glaucoma, which occurs in 1 to 20,000 to 50,000 live births. The disease is believed to be mediated by a somatic GNAQ mutation in skin or brain tissue which enhances signaling in the PKC pathway in a reported 88% (n=26) of SWS patients. (NEJM Shirley et al., May 2019). "SWS is a rare disease that can present debilitating symptoms for patients, such as choroidal hemangiomas which may lead to glaucoma. There are no current FDA approved treatments specifically developed for SWS highlighting the high unmet medical need for these patients," noted Dr. Bischoff, Ph.D.

IDE196 is a potent, selective, small molecule inhibitor of protein kinase C (PKC), which IDEAYA is evaluating in a Phase 1/2 basket trial in patients with Metastatic Uveal Melanoma or other solid tumors, such as cutaneous melanoma, having GNAQ or GNA11 hotspot mutations which enhance signaling in the PKC pathway. "We are excited to work with Boston Children's Hospital to evaluate IDE196 activity in preclinical models relevant to Sturge Weber, a rare disease believed to be driven by genetic mutation of GNAQ. This important work is part of our broader strategy to deliver precision medicine therapies for patients with GNAQ or GNA11 mutations, by targeting the underlying biology of the disease," said Yujiro S. Hata,Chief Executive Officer and President at IDEAYA Biosciences.

About IDEAYA Biosciences

IDEAYA is an oncology-focused precision medicine company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics. IDEAYA's approach integrates capabilities in identifying and validating translational biomarkers with small molecule drug discovery to select patient populations most likely to benefit from the targeted therapies IDEAYA is developing. IDEAYA is applying these capabilities across multiple classes of precision medicine, including direct targeting of oncogenic pathways and synthetic lethality which represents an emerging class of precision medicine targets.

Forward-Looking Statements

This press release contains forward-looking statements, including, but not limited to, statements related to IDE196 activity in preclinical models relevant to Sturge Weberand IDEAYA's ability to deliver precision medicine therapies. Such forward-looking statements involve substantial risks and uncertainties that could cause IDEAYA's preclinical and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including IDEAYA's programs' early stage of development, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, IDEAYA's ability to successfully establish, protect and defend its intellectual property and other matters that could affect the sufficiency of existing cash to fund operations. IDEAYA undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of IDEAYA in general, see IDEAYA's recent Quarterly Report on Form 10-Q filed on November 13, 2019 and any current and periodic reports filed with the U.S. Securities and Exchange Commission.

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IDEAYA Biosciences and Boston Children's Hospital Collaborate on Preclinical Evaluation of IDE196 for Sturge Weber Syndrome - a Rare Disease...

Study ties gene active in developing brain to autism – Spectrum

Puzzling injury: Some children who carry variants in a gene called ZNF292 have injured blood vessels in their brains.

Mutations in a gene called ZNF292 lead to a variety of developmental conditions, including autism and intellectual disability, according to a new study1.

ZNF292 encodes a protein that influences the expression of other genes. It is highly expressed in the developing human brain, particularly in the cerebellum, an area that controls voluntary movement and contributes to cognition. However, its function in neurodevelopment is unknown.

Scientists first linked ZNF292 to intellectual disability in a 2012 study. A 2018 analysis of five ZNF292 variants tied the gene to autism, but the work was preliminary2.

In the new study, researchers identified 28 people who have mutations in ZNF292. The participants come from six countries and are between 10 months and 24 years old. The group carries a total of 24 mutations in the gene, 23 of which are spontaneous meaning that they were not inherited from a parent.

The sheer number of families and children that have been identified so far has been quite high, says Ghayda Mirzaa, lead investigator and assistant professor of genetic medicine at Seattle Childrens Hospital in Washington.

All but one of the participants have intellectual disability. In total, 17 of the participants are suspected or confirmed to have autism and 9 are suspected or confirmed to have attention deficit hyperactivity disorder. All but two have speech delays, and four have had language regression or are minimally verbal.

Mirzaas team found an additional 15 people with mutations in the gene from 12 families. However, the data from these people were incomplete, so the researchers had to exclude them from the analysis. The team has connected with at least 10 other mutation carriers in the six weeks since the study was published in Genetics in Medicine.

The researchers have used their data to classify a new condition. However, it may be premature to call it a syndromic form of autism or intellectual disability, says Holly Stessman, assistant professor of pharmacology and neuroscience at Creighton University in Omaha, Nebraska, who was not involved in the work.

People with ZNF292 variants have a broad spectrum of physical traits. For instance, 11 of the people in the study have growth abnormalities such as short stature; 10 have low muscle tone; and 3 have stiff or mixed muscle tone. The researchers had access to magnetic resonance imaging scans for 17 of the participants: 9 show brain abnormalities such as atypically shaped regions, and 3 of those 9 appear to have blood-vessel injuries in the brain.

Nearly half of the participants also have unusual facial characteristics, including an undersized jaw or eyes that are unusually far apart. Vision problems, such as involuntary eye movement or crossed eyes, affect nine people in the group. Less common facial differences include prominent incisors and protruding ears.

Autism genes are often linked to a wide range of characteristics, says Santhosh Girirajan, associate professor of biochemistry and molecular biology at Pennsylvania State University, who was not involved in the study. Variability has become the rule now, rather than the exception, he says.

Mirzaa says her group plans to study more individuals with variants in ZNF292, and to investigate the genes function.

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Study ties gene active in developing brain to autism - Spectrum

Faculty and alumni appointed to state medical boards – The South End

Michigan Gov. Gretchen Whitmer appointed a number of faculty members and alumni of the Wayne State University School of Medicine to several state boards overseeing medicine and medical licensing.

Appointments to the Michigan Board of Medicine, which works with the Department of Licensing and Regulatory Affairs to oversee the practice of medical doctors ascertaining minimal entry-level competency of medical doctors and requiring continuing medical education during licensure include:

Bryan Little, M.D., Class of 1998, is the specialist in chief of Orthopedic Surgery at the Detroit Medical Center. The governor also appointed Dr. Little to the Michigan Task Force on Physicians Assistants. That entity works with the Department of Licensing and Regulatory affairs to oversee the practice of physicians assistants. The terms of both appointments expire Dec. 31, 2023.

Angela Trepanier, M.S., CGC, professor of Molecular Medicine and Genetics and director of the Genetic Counseling Masters Program at the School of Medicine. She will represent genetic counselors during her term, which expires Dec. 31, 2023.

Donald Tynes, M.D., Class of 1995, clinical assistant professor for the School of Medicine and chief medical officer of the Benton Harbor Health Center, will serve a term through Dec. 31, 2023.

Hsin Wang, M.D., Class of 1999, was appointed to the Michigan Board of Licensed Midwifery, which works with the Department of Licensing and Regulatory Affairs to establish and implement the licensure program for the practice of midwifery in the state. Dr. Wang is an obstetrician-gynecologist with the Detroit Medical Center and the director of the Pelvic Health Program for DMC Huron Valley-Sinai Hospital. Her term runs through Dec. 31, 2023.

Melissa Mafiah, M.D., Class of 2014, was appointed to the Michigan Board of Occupational Therapists for a term that expires Dec. 31, 2023. Dr. Mafiah is a physical medicine and rehabilitation physician at W.H. Beaumont Hospital. The board works with the Department of Licensing and Regulatory Affairs to promulgate rules for licensing occupational therapists and ascertaining minimal entry level competency of occupational therapists and occupational therapy assistants.

Michael Dunn, M.D., chief of Medicine at the Henry Ford West Bloomfield Hospital and the senior staff physician for the hospitals Pulmonary and Critical Care Medicine Division, is an assistant clinical professor of Medicine for the School of Medicine. He was appointed to the Michigan Board of Respiratory Care, which oversees the licensure requirements and standards for respiratory therapists. His appointment runs through Dec. 31, 2023.

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Faculty and alumni appointed to state medical boards - The South End

Why This Thematic Healthcare Could be a January Winner – ETF Trends

Due in large part to the J.P. Morgan Health Care conference in San Francisco, the biotechnology industrys marquee yearly confab, January is often a strong month for related equities and ETFs.

That conference can serve as a springboard for mergers and acquisitions activity and with the genomic space currently in the spotlight, an uptick in consolidation in that arena could benefit the Global X Genomics & Biotechnology ETF (Nasdaq: GNOM).

GNOM tracks the Solactive Genomics Index and seeks to invest in companies that potentially stand to benefit from further advances in the field of genomic science, such as companies involved in gene editing, genomic sequencing, genetic medicine/therapy, computational genomics, and biotechnology, according to Global X.

Companies are only eligible for inclusion if they generate at least 50% of their revenues from genomics related business operations. The index is market cap-weighted with a single security cap of 4.0% and a floor of 0.3%. The ETF provides exposure to CRISPR, gene editing and therapeutics companies. CRISPR, in particular, is an area to watch.

January is disproportionately represented both by a number of deals and dollar value over the past 5 years, Evercore ISI analyst Josh Schimmer wrote in a note out Wednesday morning, reports Josh Nathan-Kazis for Barrons. January has seen as high as 33% of a years total deals (5/15 in Jan 2018) and as high as 48% of a years total dollar value ($36bn/$76bn in Jan 2017).

GNOM tries to help investors take on a thematic multi-capitalization exposure to innovative elements that cover advancements in gene therapy bio-informatics, bio-inspired computing, molecular medicine, and pharmaceutical innovations. These advancements can also translate over to growth potential, potentially providing investors with long-term alpha with low correlation relative to traditional growth strategies.

Entering 2020, will companies look to keep their heads down with modest guidance? Schimmer wrote, according to Barrons. If so, we might see another choppy month, although the macro setup is quite different this time around with expectations around conservative price hikes already in sentiment.

For more thematic investing ideas, visit our Thematic Investing Channel.

The opinions and forecasts expressed herein are solely those of Tom Lydon, and may not actually come to pass. Information on this site should not be used or construed as an offer to sell, a solicitation of an offer to buy, or a recommendation for any product.

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Why This Thematic Healthcare Could be a January Winner - ETF Trends

New year health kicks are great but your environment is also vital – The Guardian

Exercising and eating better as part of our new year health kicks are great, but we should also think more deeply about the role the environment plays on our health. As a professor of environmental medicine, I believe this is an exciting new area of study that will play a big part in the future of personalized medicine.

Consider this, every day we are bombarded with messages: genes that cause cancer, supplements that prevent Alzheimers disease, diets that prevent asthma, chemicals that make us gain weight. But while headlines frequently proclaim game changing new findings, over the last 20 years in the US and Europe our health status as a population has seriously deteriorated. Rates of obesity, diabetes, heart disease, cancer and learning disorders continue to rise. Genetic variation may be part of the puzzle that explains why we get sick, but clearly there are missing pieces.

After all, 20 years of increasing obesity and diabetes represents only a single generation. If our genes didnt change in the last 20 years, then our environment must have.

Genes never work in isolation. Instead, they determine how we react to our diet, social surroundings, physical environment, infections and chemical exposures. Environment is the missing piece of the puzzle.

The old 20th-century concept of nature v nurture needs to be redefined, as genetics and environment do not compete, they work hand in hand, sometimes to our benefit and sometimes to our detriment. The correct formula is really nature times nurture. Right now the nurture part of that equation is largely unknown, but that may soon change.

Recently, a new concept has arisen, the science of the exposome: the measurement of all the health-relevant environmental factors across the lifetime.

The exposome is to our environment what genomics is to our genetics. Most of what we know about environment and health is still a black box consisting of yet to be discovered risk factors we too often attribute to bad luck ie because we dont measure the environmental cause, the problem appears random.

But most of what we now understand about genetics was also a black box in the 20th century.

Physicians see the role of environment daily even if it is not clear to them that environment is the cause. For example, a child with autism develops more frequent combative oppositional behaviors and emotional outbursts. An adult with diabetes cant seem to control her blood sugar despite higher doses of insulin. A newborn is born with blue skin but a normal heart.

For each of these cases, sequencing the genome would not have identified the cause. The autistic child had lead poisoning because of pica brought on by autism, the diabetic adult used perfumes high in phthalates, chemicals that affect metabolism and the newborn baby drank formula mixed with well water contaminated by fertilizer runoff that reacted with his hemoglobin.

In each case, genomics would not have given us the correct answer, but if we had the tools to measure the exposome, we would have made the correct diagnosis. Just as importantly, because the underlying causes were environmental, we can treat the problem with interventions.

Furthermore, in most diseases, environment and genetics work in combination. Its very rare to have a genetic variant that causes Alzheimers disease, but it is fairly common to have a genetic variant that makes us susceptible to environments that can cause Alzheimers. The different between those with the genetic variant who get sick and those who dont is their different environments.

Imagine a visit to your physician in which you begin by handing over your smartwatch to have its data downloaded, followed by a blood draw to measure your chemical environment and nutritional status, then you update your lifetime home address and occupational history into a secure computer that houses your genomic data. This then computes your personalized risk score for heart disease, diabetes and other diseases. Or, if you already have one of these diseases, computes the ideal treatment regimen based on this big data. This is how we will be able to personalize medicine.

We are not there yet, but the technology to measure the exposome is far more advanced than the general public, and even many researchers, realize. There are now lab tests that can demonstrate the presence of thousands of chemicals in our bodies and satellites that record our daily weather, air pollution, light exposure and built environment. Public records have data on water quality, age of housing, local crime statistics, outdoor noise levels and even where disease clusters are occurring. Cellphones are ubiquitous and can link our daily behavior and movement patterns with the quality of the local air and water while simultaneously measuring our heart rate, physical activity and sleep quality.

Computational science has advanced to a point where storage of terabytes of data is routine and computer clusters are found in every major university and methods to bring these databases together are no longer science fiction. Artificial intelligence and other big data approaches to genomics also provide a roadmap for analyzing exposomic data.

Understanding how environment affects your health will empower people to make the changes in their lifestyle that will matter most. To understand what food to buy, which fragrances to avoid, where and when to exercise, etc. All the pieces to solve this puzzle are beginning to come together. What is needed is the grand vision to invest in and integrate exposomic science into public health and clinical medicine. This is the final piece of the puzzle. Once we understand our exposome and integrate it with our genome, we will finally understand why and how chronic diseases have become so common and how we can start to reverse their trends in society.

Dr Robert Wright is a pediatrician, medical toxicologist, environmental epidemiologist and director of the Institute for Exposomic Research at the Icahn School of Medicine at Mount Sinai

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New year health kicks are great but your environment is also vital - The Guardian

Biofidelity and Agilent complete successful molecular assay study for rapid and accurate detection of key lung cancer mutations – BioSpace

Biofidelity assay has potential to make high precision, cost-effective and non-invasive diagnosis more widely available, improving treatment and patient outcomes

Cambridge, UK, 9th January 2020 Biofidelity Ltd, a company developing high performing novel molecular assays for the detection of targeted, low-frequency genetic mutations, today announced the successful completion of a study to detect key lung cancer mutations in collaboration with Agilent Technologies, a global leader in life sciences, diagnostics, and applied chemical markets.

The collaboration, using an assay developed by Biofidelity, demonstrated an improvement in sensitivity of 50 times that achieved with current FDA-approved PCR-based diagnostics, matching that of specialized NGS assays, which require error-correction technology, while providing a dramatic simplification of workflows from more than 100 steps, to just 4 (four). Assays were performed using standard laboratory instrumentation, demonstrating the potential for straightforward adoption of Biofidelitys panels in decentralised testing laboratories around the world.

As well as extremely high sensitivity, 100% specificity was achieved in the detection of multiplexed panels of mutations from both tissue and plasma, with no false positives observed across more than 750 assays. Analysis of results is also dramatically simpler than sequencing-based assays, providing physicians a clear, simple, actionable result, with a turnaround time of less than 3 hours, making the Biofidelity assay suitable for recurrent patient monitoring.

Genetic testing for lung cancer mutations is usually carried out through invasive tissue biopsy, an expensive procedure carrying significant risk for patients with advanced disease. Up to 10% of such tests fail due to the lack of sensitivity of current testing solutions and poor sample quality.

Liquid biopsy, or testing directly from the patients blood, offers a non-invasive alternative with significant potential benefits to patients. However, its use has been limited by the lack of cost-effective, robust and rapid tests which are sufficiently sensitive to enable detection of the very small fractions of tumor DNA present in such samples.

Of the nearly 2 million new cases of non-small-cell lung cancer (NSCLC) diagnosed each year worldwide, fewer than 5% of patients receive high-sensitivity, non-invasive genetic testing. The assay developed by Biofidelity could provide a simple solution, enabling access to high-precision genetic testing for more than 1.7m new NSCLC patients every year with a test that outperforms DNA sequencing in a fraction of the time.

Work was supported by InnovateUK grant number 105202 as part of the Investment Accelerator: Innovation in Precision Medicine program.

Dr Barnaby Balmforth, Chief Executive Officer of Biofidelity, commented: Our goal is to improve patient outcomes in oncology by enabling much greater access to the highest precision diagnostic tests. This collaboration with Agilent in lung cancer has again demonstrated that Biofidelitys molecular assays dramatically increase the effectiveness and speed of diagnosis, supporting early detection of disease, better targeting of therapies and improved patient monitoring. By combining diagnostic outperformance and rapid results in a simple, cost-efficient format using existing instrumentation, we believe we have the potential to bring high precision testing to many more NSCLC patients, substantially reducing the need for invasive biopsies.

Tad Weems, Managing Director, Agilent Early Stage Partnerships, commented: As both a scientific collaborator and an investor in the company, Agilent has been impressed by the data from Biofidelitys assays, which detected a selection of NSCLC DNA mutations at extremely low frequencies in both tissue and plasma samples without the need for DNA sequencing. Biofidelitys assays are specific and sensitive, with the potential to provide improved and rapid routine cancer diagnostics.

Notes To Editors

About Biofidelity

Biofidelity has developed a molecular assay with a simple workflow and fast time-to-result which can transform the detection of genetic abnormalities within a sample by reliably detecting large panels of DNA mutations at extremely low frequencies.

This assay has a simple workflow and is suitable for routine use in diagnostics labs around the world, without the need for investment in new instrumentation or infrastructure.

Biofidelity is developing genetic panels for use in precision medicine and patient monitoring across a range of diseases including NSCLC and colorectal cancer

Located in Cambridge, UK, Biofidelity is a private company founded in 2019.

For more information, visit http://www.biofidelity.com, or follow us on LinkedIn: Biofidelity.

Issued for and on behalf of Biofidelity by Instinctif Partners.For more information please contact:

BiofidelityDr Barnaby Balmforth, CEOT: +44 1223 358652E: info@biofidelity.com

Instinctif PartnersTim Watson / Genevieve WilsonT: +44 20 7457 2020E: Biofidelity@instinctif.com

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Biofidelity and Agilent complete successful molecular assay study for rapid and accurate detection of key lung cancer mutations - BioSpace

New MD Treatments the Main Goal of Astellas, Audentes Merger – Muscular Dystrophy News

Astellas Pharma recentlyagreed to acquire Audentes Therapeutics, a move it expects will result in faster development of potentially best-in-class therapies for rare neuromuscular diseases, including muscular dystrophy (MD).

Audentes vectorized exon-skipping technology which uses a modified adeno-associated virus (AAV) vector to allow cells to skip over mutated sections of genes will complement Astellas own work, Kenji Yasukawa, president and CEO of Astellas, said in a press release.

Recent scientific and technological advances in genetic medicine have advanced the potential to deliver unprecedented and sustained value to patients, and even to curing diseases with a single intervention, Yasukawa said.

Audentes has developed a robust pipeline of promising product candidates which are complementary to our existing pipeline, including its lead program AT132, he added. By joining together with Audentes talented team, we are establishing a leading position in the field of gene therapy with the goal of addressing the unmet needs of patients living with serious, rare diseases.

The technology uses the modified AAV vector to deliver small molecules antisense oligonucleotides complementary to the RNA sequence of a gene of interest, which allow cells to skip over mutated exons while they are producing proteins.

Exons are the coding regions of genes that provide instructions to make proteins.

Audentes had started developing several therapies for Duchenne muscular dystrophy (DMD) based on its exon-skipping technology. These include AT702, AT751 and AT753.

All three treatment candidates use the same AAV delivery vector. However, as they target different DMD gene exons, the potential therapies are intended for distinct subgroups of patients. AT702 is designed to skip exon 2 and is meant for those who either have duplications in exon 2 or mutations in exons 1-5. AT751 is designed for those with mutations in exon 51, and AT753 for people with alterations in exon 53.

Audentes had also started developing and testing AT466, an experimental treatment for myotonic dystrophy type 1.

The acquisition also gives Astellas direct access to AT132, Audentes lead gene therapy candidate for the treatment ofX-linked myotubular myopathy.

AT132 uses an AAV8 viral vector to deliver a functional copy of the MTM1 gene to muscle cells. This enables the production of myotubularin, an important enzyme for the development and maintenance of muscle cells.

Matthew R. Patterson, chairman and CEO of Audentes, said his company is very pleased with the agreement. With its focus on innovative science and a global network of research, development and commercialization resources, we believe that operating as part of the Astellas organization optimally positions us to advance our pipeline programs and serve our patients, he said.

Under the terms of the agreement, Audentes will become an independent subsidiary of Astellas and will have access to scientific resources to accelerate the development and manufacturing of the combined product pipeline. The transaction, worth $3 billion, is expected to take place early this year.

Joana is currently completing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. She also holds a BSc in Biology and an MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells cells that make up the lining of blood vessels found in the umbilical cord of newborns.

Total Posts: 42

Jos is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimers disease.

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New MD Treatments the Main Goal of Astellas, Audentes Merger - Muscular Dystrophy News

Physicians’ Education Resource Presents the 2nd Annual Precision Medicine Symposium in New York City – BioSpace

We look forward to hosting our precision medicine conference for the second year in a row, said Phil Talamo, president of PER. This meeting is designed to take a targeted approach to treatment, focusing on how biomarkers and testing strategies can personalize care to patients, often times in a tumor agnostic setting.

Across a two-day, pan-tumor symposium, expert faculty will cover the latest topics in solid and liquid tumors, including lung, breast, gastrointestinal, genitourinary, skin cancers and hematologic malignancies. The educational meeting will feature high-impact sessions and keynote lectures that will focus on practical takeaways regarding the latest updates in next-generation sequencing, liquid biopsy and cytogenetic testing. The program will review updates in targeted treatment, including tumor-agnostic indications based solely on genomic markers and other biomarkers. The tumor board overall will emphasize the role of advanced genetic panel testing and the use of targeted therapies, with a focus on data that is most relevant to patient care.

For more information and to register, click here.

About Physicians Education Resource (PER)

Since 1995, PER has been dedicated to advancing cancer care through professional education and now advances patient care and treatment strategies on a wide variety of chronic illnesses and diseases. In 2016, PER initiated continuing medical education (CME) programming in the cardiovascular and endocrinology areas. While expanding into topics outside of oncology, PER stands as the leading provider of live, online and print CME activities related to oncology and hematology. The high-quality, evidence-based activities feature leading distinguished experts who focus on the application of practice-changing advances. PER is accredited by the Accreditation Council for Continuing Medical Education and the California Board of Registered Nursing. PER is a brand of MJH Life Sciences, the largest privately held, independent, full-service medical media company in North America dedicated to delivering trusted health care news across multiple channels.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200109005679/en/

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Physicians' Education Resource Presents the 2nd Annual Precision Medicine Symposium in New York City - BioSpace

A Genetic Mutation Is Responsible for Mysterious Deaths in the Amish Community, Researchers Say – Gizmodo

An Amish boy and girl walking along the road near Paradise, Pennsylvania Photo: Getty Images

In a new paper this week, doctors at the Mayo Clinic say theyve uncovered the cause of a mysterious heart condition that had suddenly killed over a dozen young, healthy members of a tight-knit Amish community. The culprit? A previously undiscovered genetic mutation that runs in families.

Study author Michael Ackerman, a cardiologist and professor at the Mayo Clinic College of Medicine and Science, is also director of the Mayo Clinic Windland Smith Rice Sudden Death Genomics Laboratory. For years, the lab has investigated cases in which seemingly healthy people died with no clear cause, hoping to unearth new ways our genes can send us to an early grave. In many of these cases, peoples hearts simply stopped beating, a condition otherwise known as cardiac arrest.

According to Ackerman, the journey to unraveling this particular mystery was a long one.

The medical examiner first contacted me and my research team over 15 years ago, after the deaths of two Amish siblings during recreational play over four months time, Ackerman told Gizmodo via email. For me, in situations like these, it is either foul play or genetic. [But] there was no way based on interviews with the family that this was foul play, so we searched for the genetic cause of sudden cardiac death.

As is often the case with smaller, isolated communities of people, the Amish have more in common genetically with one another than people living in a typical modern community do with their neighbors. Unfortunately, the less genetically diverse a population is, the easier it is for harmful genetic conditions to emerge and be passed down to the next generation. These conditions are often recessive, meaning it takes having two copies of the unlucky genetic variationone inherited from each parentfor symptoms to show up. Those who carry just one copy of the bad variation usually end up with no health problems, and even if they have children with another carrier, theres only a 25 percent chance a child of theirs will have both copies.

From the start, Ackerman and his team suspected a recessive mutation could be responsible for what happened to the children, since their family tree had a history of closely related ancestors while the parents themselves seemed perfectly healthy. But their initial sweep failed to turn up potential clues.

Tragically, two more children in the family would later die of sudden cardiac arrest as well, six and eight years after the first deaths, respectively. All of them, no younger than 12, had been playing or exercising right before their deaths.

By the time of these newer deaths, though, genetic technology had advanced enough for the team to try looking again. In particular, they were now able to scan a persons entire exome, the bits of DNA that actually program our cells to make the building block proteins we need to live. And this time, they found a likely suspect: a duplication of DNA found in segments of the RYR2 gene as well as in another region that controls its expression.

The RYR2 gene helps regulate our heart muscles calcium release channels (CRC). These channels need to carefully manage the flow of calcium in and out of heart cells to keep the organ healthy and beating as it should during times of rest and stress alike. People are already known to have genetic mutations that can leave them with overactive CRCsa condition that also raises their risk of sudden cardiac death. But this specific mutation seems to create the opposite problem, leaving victims with too few CRCs.

As the team theorized, the children who had died all had two copies of the mutation, while the parents and unaffected siblings all had either one or no copies. They then came across a second large Amish family, unrelated to the first, that also had a history of healthy young people suddenly dying of or barely surviving cardiac arrest. And when the second family was tested, nearly all of those with two copies of the mutated gene had died or developed these symptoms.

The teams findings were published Wednesday in JAMA Cardiology.

Ultimately, through a combination of technology and tenacity, we found the answer, Ackerman said.

The mutation and the condition it causescoined calcium release channel deficiency syndrome by the teamstill needs to be studied by other researchers before it can be confirmed as a genuine disorder. But so far, 23 people have been identified with the mutation, with 18 having died, across the two families, while more relatives are being tested by the team. Ackerman said his teams work has been greatly appreciated and celebrated by the families.

The power of closurefiguring out the truth about what was behind all of these tragediesand claritybeing able to figure out who does and who does not have these markersis incredible, as you can imagine, he said.

Our genes usually influence our health insubtle ways. Even people who have a clearly troublesome mutation dont always become seriously sick. But conventional tests havent been able to tell when someone with the condition will have heart troubles. And given how quickly lethal it can be, Ackerman expects that affected individuals will need an implantable cardioverter-defibrillator that can intervene when the heart loses control of itself. More importantly, though, we can now find these people before its too late.

Although we could not save the lives of these precious children and teenagers and young adults, we now have a diagnostic biomarker such that no more deaths from CRC deficiency syndrome should have to ever occur again, Ackerman said.

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A Genetic Mutation Is Responsible for Mysterious Deaths in the Amish Community, Researchers Say - Gizmodo

Kyoto Univ.-distributed iPS cells found with abnormalities after differentiation – The Mainichi

(Mainichi)

Some iPS cells for regenerative medicine, distributed by a stock project at Kyoto University's Center for iPS Cell Research and Application (CiRA), showed cancer-related genetic and chromosomal abnormalities when differentiated to the target cells, several sources close to the project revealed.

Some of the iPS cells, even those produced at the same time, showed various abnormalities while others did not, depending on the research institution they were distributed to, prompting experts to voice concerns over their safety. The CiRA has acknowledged the facts, and the cells that developed abnormalities were not used in patients.

The project stockpiles iPS cells provided by the same suppliers at the same time in a cell line. In clinical research and a trial, iPS cells and differentiated cells go through genome analysis, and are transplanted into mice to check whether they turn cancerous. It is then decided which cell line should be distributed to implementing agencies.

Of the 27 cell lines distributed since August 2015, test results were revealed for four. Of these, abnormalities were found in two cell lines. The two cell lines were distributed in several containers to two research institutions, respectively, and were differentiated to the same target cells at each institution.

For one of the cell lines, one institution found a genetic abnormality in relation to cancer, while the other found a numerical disorder in the chromosome. For the other cell line, one institution found a different genetic abnormality, while the other institution did not find any irregularities. Furthermore, the institution that found the abnormality did not find any problems in the cells kept in a different container.s

Genetic abnormalities included a high-risk abnormality, similar to those found in humans with cancer. When implanted in mice, abnormal tissue growth that cannot be seen with normal cells was confirmed.

"No matter what kind of cell, an error could occur during the process of cultivation and differentiation," said specially appointed professor and manufacturing supervisor Masayoshi Tsukahara of the iPS cell stock project. He explained, "There's no other choice but to conduct careful tests before putting them to use."

Several experts in Japan, however, expressed concerns that safety cannot be ensured if test results vary depending on containers.

Michael Snyder, professor at Stanford University's School of Medicine and the director of the Center for Genomics and Personalized Medicine, pointed to the need to evaluate the matter in an open discussion.

(Japanese original by Momoko Suda, Science & Environment News Department)

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Kyoto Univ.-distributed iPS cells found with abnormalities after differentiation - The Mainichi

The Importance of Understanding TargetProtein Interactions in Drug Discovery – Technology Networks

Youre unwell, you see a doctor, they prescribe you a medicine and you take it. But how exactly is that drug having an effect? What is its mechanism of action? Drugs exhibit their effects through specific protein-target interactions.

But in some cases, there may not be a treatment available. In approximately 30% of cases, drugs fail during clinical development, and toxicity which can be caused by off-target binding is often to blame.

Andrew Lynn, Chief Executive Officer at Fluidic Analytics discusses why understanding protein-target interactions is so important, the common challenges researchers face when attempting to determine these interactions, and touches on the relationship between the drug "attrition rate" crisis and the off-target effects of drugs.

Laura Lansdowne (LL): Could you discuss the importance of understanding proteintarget interactions in drug discovery, and the implications of not knowing your target?Andrew Lynn (AL): Understanding proteintarget interactions is crucial we are talking about the difference between finding a lifesaving drug/therapy and wasting hundreds of millions of dollars developing a drug with the wrong mechanism of action.A recent paper from Jason Sheltzers group showed that ten anticancer drugs undergoing clinical trials had a completely different mechanism of action from the one originally attributed to them. Briefly, when the protein targeted by each of the drugs was removed from cancer cells, the group expected the drugs to stop working. But what they found was that the drugs continued to work as normal and thus had to be working through off-target binding.This is crucial because it means potentially there are many more drugs out there that are working through off-target binding; it also means that many other drug candidates that have previously been disregarded may have unrecognized promise. This problem is about to become even more acute as research expands into conditions with difficult targets like Alzheimer's disease.The way in which we discover the exact mechanism of action between proteins and potential drug candidates needs better technologies for characterizing on-target and off-target interactions We cannot discover new information relying solely on technologies that have fallen short for decades.LL: What challenges do drug discovery researchers face when trying to identify targetprotein interactions?AL: Drug discovery and development is a lengthy, complex and costly process with a high degree of uncertainty whether a drug will succeed. The two biggest challenges are: First, not understanding the pathophysiology of many disorders, such as neurodegenerative disorders, which makes target identification challenging. Second, the lack of validated diagnostic and therapeutic biomarkers to objectively detect and measure biological states.At the heart of both challenges is the ability to characterize protein-drug target interactions. Unfortunately, the methods currently employed by researchers to do this research are outdated.

An example of this can be seen when scientists try to characterize interactions involving intrinsically disordered proteins (IDPs) such as the ones associated with Parkinsons disease. Current characterization methods modify proteins by fixing them to a surface or putting them in artificial environments. So, its no surprise that many drugs are great at targeting proteins with these modifications but poor at targeting these same proteins as they exist in vivo in solution and not tethered to an artificial surface.

This is why were building new tools and methods for researchers to more accurately characterize binding events in solution: to better understand how drugs interact with their protein targets in their native environment.

LL: What is microfluidic diffusional sizing and how can this be used to measure the binding affinity of proteinprotein interactions?AL: Microfluidic diffusional sizing (MDS) characterizes proteins and their interactions in solution based on the size (or more specifically hydrodynamic radius) of proteins and protein complexes as they diffuse within a microfluidic laminar flow. Characterizing in solution avoids artefacts from surfaces or matrices; gathering information about size to give crucial insights into stoichiometry, on- and off-target binding, oligomerization and folding.

MDS can be used to measure binding affinity by tracking changes in the size of a protein as it binds at different concentrations. The size of the complex can also give a strong indication of whether the protein is forming a protein-target complex at the expected size (on-target binding) or something with a completely different or unexpected size (off-target binding). A major additional advantage of MDS is that, because of the absence of surfaces or matrices, it can be used to characterize binding involving difficult targets such as intrinsically disordered proteins and membrane proteins.

LL: Could you discuss the relationship between the drug "attrition rate" crisis and the off-target effects of drugs?AL: Compound failure rates due to toxicity before human testing is very high. A recent review from a top-20 pharma company cited toxicity as the reason why, between 2005-2010, 82% of drugs were rejected at the preclinical stage and 35% in phase 2a. Overall, concerns surrounding toxicity account for as much as 30% of drug attrition occurring during the clinical stage of development.For many potential drugs, toxicity is due to off-target binding. By employing new methods to characterize drug candidates binding to protein targets in native conditions, we can identify off-target binding more effectively. This could help save billions of dollars in development costs and reduce the attrition rate we are currently facing.

LL: There has currently been very limited success in the development of effective therapies for Alzheimers disease (AD). Could you touch on some of the successes and highlight the molecules of interest in AD as well as the challenges related to their study.AL: One recent success is the anti-amyloid drug, aducanumab. After Biogen re-examined the data from the clinical trials, they found that exposure to high doses of Aducanumab reduced clinical decline in patients exhibiting early stages of Alzheimers disease.If approved, aducanumab would become the first therapy to slow the cognitive decline that accompanies Alzheimer's disease. This a massive step forward and a much-needed source of hope for patients and their families.But aducanumab doesnt cure Alzheimers disease. A major challenge impeding the development of further AD drugs is the ability to understand the mechanism of action via which candidate drugs interact with targets. Amyloid- is known to be a particularly difficult-to-characterize peptide, and even aducanumab doesnt have a well-understood mechanism of action. Any breakthroughs in being able to characterize how it or other Alzheimers disease drugs interact with difficult targets would be a major breakthrough in drug development.However, the majority of Alzheimers patients do not carry the dominantly inherited genetic mutation for the disease, and we dont know why amyloid proteins aggregate within their brains.

It follows that there wont be a single cause but rather many causes. Thus, the common consensus is that there wont be a single miracle drug that cures Alzheimers disease for everyone.

Andrew Lynn was speaking with Laura Elizabeth Lansdowne, Senior Science Writer, Technology Networks.

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The Importance of Understanding TargetProtein Interactions in Drug Discovery - Technology Networks

These 2 Stocks Will Fall After the New Year – Motley Fool

For all of the hype surrounding gene therapy and gene editing, the precision genetic medicine approach that turned in the best 2019 may have been RNA interference (RNAi). The gene-silencing technique earned its first regulatory approval for a novel targeted delivery method. That may not sound like much to get excited about, but it promises to open up numerous high-value opportunities for RNAi drug developers.

The approval, coupled with promising early-stage clinical results and massive partnership deals, explains why Arrowhead Pharmaceuticals (NASDAQ:ARWR) and Dicerna Pharmaceuticals (NASDAQ:DRNA) erupted higher in 2019. The RNAi drug developers saw their market valuations increase by 450% and 106%, respectively, last year.

While both companies have promise, thepharma stocks are likely to fall in early 2020. What does that mean for investors with a long-term mindset?

Image source: Getty Images.

Shares of Arrowhead Pharmaceuticals had a pretty good first nine months of 2019, but the most impressive gains came in the fourth quarter. The RNAi stock gained heading into the American Association for the Study of Liver Diseases (AASLD) Annual Meeting in November. Investors were eagerly awaiting the results of two drug combinations being developed to treat chronic hepatitis B (CHB) by Johnson & Johnson (NYSE:JNJ) subsidiary Janssen.

The results lived up to the hype. The most impressive data came from a triple combination of an RNAi drug from Arrowhead Pharmaceuticals (now called JNJ-3989), an antiviral drug from Johnson & Johnson (JNJ-6379), and a nucleos(t)ide analog (NA). After 16 weeks of treatment, all 12 individuals in the study achieved at least a 90% reduction in two biomarkers of hepatitis B virus activity.

Investors gobbled up shares of Arrowhead Pharmaceuticals because the triple combination appears to be the industry's best hope for developing the first functional cure for CHB (although it can't be called a functional cure just yet).

Additionally, the RNAi drug candidate in the triple combination is based on a targeted delivery platform called TRiM. The approach is simple: The gene-silencing payload is attached to a special sugar that's absorbed by the liver. Since many RNAi drug candidates need to interact with DNA in liver cells, and the sugars are easily metabolized by the liver (improving safety over prior-generation lipid nanoparticle delivery vehicles), it's a perfect pairing.

It helps that just a few weeks after AASLD, Givlaari from Alnylam Pharmaceuticals (NASDAQ:ALNY)became the first RNAi drug candidate based on a conjugated-sugar delivery method to earn regulatory approval. It also helps that Dicerna Pharmaceuticals landed two massive partnerships in the fourth quarter of 2019 -- both based on its own conjugated-sugar delivery platform. Following those deals, there's now considerable overlap between the pipelines of Arrowhead Pharmaceuticals and Dicerna Pharmaceuticals, which are both all-in on targeted delivery.

RNAi Developer

Partner, Indication

Financial Terms

Arrowhead Pharmaceuticals

Johnson & Johnson, hepatitis B

$175 million up front, $75 million equity investment, up to $1.6 billion in milestone payments, royalties

Arrowhead Pharmaceuticals

Johnson & Johnson, undisclosed

Up to $1.9 billion in total milestone payments for up to three additional drug candidates, royalties

Arrowhead Pharmaceuticals

Amgen, cardiovascular disease

$35 million up front, $21.5 million equity investment, up to $617 million in milestone payments, royalties

Dicerna Pharmaceuticals

Roche, hepatitis B

$200 million up front, up to $1.47 billion in milestone payments, royalties

Dicerna Pharmaceuticals

Novo Nordisk, various liver-related cardio-metabolic diseases

$175 million up front, equity investment of $50 million, an additional $75 million over the first three years, up to $357.5 million per drug candidate, royalties

Data source: Press releases, filings with the Securities and Exchange Commission.

Despite all of the progress from both Arrowhead Pharmaceuticals and Dicerna Pharmaceuticals in 2019, both companies are likely to fall back to Earth a bit following giant run-ups.

Consider that Arrowhead Pharmaceuticals is valued at $6.3 billion at the start of 2020. The company's most advanced drug candidate, ARO-AAT, recently began dosing patients in a phase 2/3 trial in a rare genetic liver disease associated with alpha-1 antitrypsin (AAT or A1AT) deficiency. While that study can be used for a new drug application (NDA), and the drug candidate could achieve over $1 billion in peak annual sales, that alone doesn't support a $6.3 billion valuation.

Meanwhile, the triple combination in CHB could support a market valuation well above $6 billion, especially if it proves to be a functional cure. The drug candidate could eventually earn peak annual sales of over $10 billion in that scenario. But the recent gains were spurred by results in only 12 individuals after 16 weeks of follow-up. A phase 2b trial now underway will enroll 450 patients and follow them for two years. In other words, there's plenty of time for investors to take some gains off the table.

Dicerna Pharmaceuticals is valued a little more reasonably, at just $1.5 billion, but it has only one drug candidate in mid- or late-stage clinical trials. The pipeline programs at the center of recent deals with Roche and Novo Nordisk are still in preclinical development or phase 1 studies; there's little to no clinical data from the programs for investors to survey. While the business will be flush with cash after receiving up-front payments in the coming months, there's a lot of work to be done.

To be clear, both Arrowhead Pharmaceuticals and Dicerna Pharmaceuticals hold a lot of promise. Targeted delivery of RNAi drug payloads into the liver could open up considerable opportunities to treat -- for the first time, in some cases -- rare diseases, viral infections, and cardiovascular ailments. Both companies have even demonstrated early work to target gene-silencing payloads to other cell types, such as muscle tissues, which may open up additional avenues for drug discovery and development.

However, these two RNAi stocks have fallen 10.7% and 12.3%, respectively, since Dec. 3 -- and both are likely to fall a bit further in early 2020. If and when that occurs, investors may want to give each stock, especially Arrowhead Pharmaceuticals, a closer look.

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These 2 Stocks Will Fall After the New Year - Motley Fool

Webinar: How Providers are Harnessing the Power of Genomics to Improve Community Health – ModernHealthcare.com

James Lu, M.D., PH.D.Co-founder & Senior Vice President of Applied GenomicsHelix

James is a co-founder and SVP of Applied Genomics at Helix, a population genomics company with a mission to empower every person to improve their life through DNA. Helix is accelerating the integration of genomic data into clinical care and broadening the impact of large-scale population health programs by providing comprehensive expertise in DNA sequencing, bioinformatics, and individual engagement. Powered by our proprietary Exome+assaya panel-grade exome enhanced by more than 300,000 informative non-coding regionsHelix partners with health systems to provide a scalable solution which enables the discovery of medically relevant, potentially life-saving, genetic information. Additionally, Helix offers a suite of DNA-powered products for continued individual engagement and discovery.

At Helix, James is responsible for the scientific teams which include bioinformatics, laboratory operations, regulatory, quality, translational research and policy teams.

Prior to Helix, James was a faculty member at Duke University where he focused on translational genomics and machine learning methodologies for electronic medical records. James has also explored a broad range of research topics in population genetics, Mendelian genomics, and computational psychiatry and has published dozens of papers in journals such as Nature, the New England Journal of Medicine and the Journal of Machine Learning Research.

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Webinar: How Providers are Harnessing the Power of Genomics to Improve Community Health - ModernHealthcare.com

Genomics and Medicine | NHGRI

It has often been estimated that it takes, on average, 17years to translate a novel research finding into routine clinical practice. This time lag is due to a combination of factors, including the need to validate research findings, the fact that clinical trials are complex and take time to conduct and then analyze, and because disseminating information and educating healthcare workers about a new advance is not an overnight process.

Once sufficient evidence has been generated to demonstrate a benefit to patients, or "clinical utility," professional societies and clinical standards groups will use that evidence to determine whether to incorporate the new test into clinical practice guidelines. This determination will also factor in any potential ethical and legal issues, as well economic factors such as cost-benefit ratios.

The NHGRIGenomic Medicine Working Group(GMWG) has been gathering expert stakeholders in a series of genomic medicine meetingsto discuss issues surrounding the adoption of genomic medicine. Particularly, the GMWG draws expertise from researchers at the cutting edge of this new medical toolset, with the aim of better informing future translational research at NHGRI. Additionally the working group provides guidance to theNational Advisory Council on Human Genome Research (NACHGR)and NHGRI in other areas of genomic medicine implementation, such as outlining infrastructural needs for adoption of genomic medicine, identifying related efforts for future collaborations, and reviewing progress overall in genomic medicine implementation.

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Genomics and Medicine | NHGRI

Free Gene Therapy Available for Patients with Alzheimer’s – HealthITAnalytics.com

January 03, 2020 -Maximum Life Foundation (MaxLife), a non-profit organization focused on aging research, is providing a promising free gene therapy for ten patients with Alzheimers disease.

According to the Alzheimers Association, Alzheimers disease is the sixth leading cause of death in the US. Over five million Americans have the condition, leading to costs of $277 billion a year.

With this gene therapy, researchers have seen improvements in Alzheimers symptoms and the recovery of normal brain functions in experiments with mice. In human cell experiments, the therapy had the same effects through the rejuvenation of microglia, the brains first line of defense against infection, and neurons.

In August 2018, a patient received a low dose of the therapy with no adverse side effects. To date, the patients disease hasnt progressed.

MaxLife will grant 100 percent of the therapy costs to help bring pioneering gene therapy to cure this disease and make Alzheimers disease a thing of the past, said David Kekich, MaxLifes CEO.

Studies have proven that aging is the leading factor in many life-threatening diseases, including Alzheimers. This new gene therapy aims to treat the cellular degeneration caused by aging.

The new treatment is offered by Integrated Health Systems, a gene therapy facilitator that is seeking to treat other adult aging-related diseases with no known cure, including sarcopenia, chronic kidney disease, and atherosclerosis.

This technology could halt many of the big age-associated killers in industrialized countries, said Kekich. Compassionate care helps patients with no other option to get access to experimental therapies that may benefit both themselves and society as a whole.

Other healthcare organizations have stressed the need to leverage gene therapies and precision medicine to improve treatment for Alzheimers and other diseases. A recent study published in Frontiers in Aging Neuroscience discussed how precision medicine tactics will help improve cognitive disease treatment.

Taking a precision medicine approach, the question is no longer Does treatment work? but Who does treatment work for? Identifying the characteristics of non-responders becomes as important as responders in understanding the impact of a particular intervention, the team said.

Such an approach may result in considerable health benefits by allowing more effective selection of individuals for treatments based ona prioriknown profiles of disease risk and their potential response to treatment.

Researchers at Massachusetts General Hospital (MGH) also recently discovered that certain genetic variants may help protect individuals against Alzheimers disease, a finding that could hold important implications for precision medicine therapies.

The team studied a patient who carried a mutation in a gene known to cause early onset Alzheimers but didnt show signs of mild cognitive impairment until her seventies. This is nearly three decades after the typical age of onset. Evaluating this patient, and patients like her, could help researchers understand more about the progression of Alzheimers.

This single case opens a new door for treatments of Alzheimers disease, based more on the resistance to Alzheimers pathology rather than on the cause of the disease. In other words, not necessarily focusing on reduction of pathology, as it has been done traditionally in the field, but instead promoting resistance even in the face of significant brain pathology, said Yakeel T. Quiroz, PhD, clinical neuropsychologist and neuroimagingresearcher at MGH.

With the new gene therapy, MaxLife will add to the growing body of research exploring the use of precision medicine and genetics in chronic disease treatment.

If we can prove a benefit to patients that have no other option now, we can potentially treat Alzheimers disease in people in early to mid-stage Alzheimers, finally creating effective medicine at the cellular level, states Kekich. If successful, this treatment could potentially be used on other diseases such as Parkinsons and ALS.

To apply for a free therapy or for more information, click here.

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Free Gene Therapy Available for Patients with Alzheimer's - HealthITAnalytics.com

Chinese Researcher Who Created Gene-Edited Babies Sentenced To 3 Years In Prison – NPR

He Jiankui, a Chinese researcher shown here at a conference last year in Hong Kong, has been sentenced to three years in prison. Kin Cheung/AP hide caption

He Jiankui, a Chinese researcher shown here at a conference last year in Hong Kong, has been sentenced to three years in prison.

Updated at 1:30 p.m. ET

A Chinese scientist who shocked the medical community last year when he said he had illegally created the world's first gene-edited babies has been sentenced to three years in prison by a court in southern China.

He Jiankui announced in November 2018 that he had used a powerful technique called CRISPR on a human embryo to edit the genes of twin girls. He said he modified a gene with the intention of protecting the girls against HIV, the virus that causes AIDS. Many scientists expressed concerns about possible unintended side effects of the genetic changes that could be passed down to future generations.

Last fall, He also indicated there might be another pregnancy involving a gene-edited embryo. The court indicated that three genetically edited babies have been born.

The closed court in Shenzhen found He and two colleagues guilty of illegal medical practice by knowingly violating the country's regulations and ethical principles with their experiments, Xinhua news agency reported. It also ordered He to pay a fine of about $430,000.

He's colleagues, Zhang Renli and Qin Jinzhou, were handed lesser sentences and fines.

"None of the three defendants acquired doctor's qualifications. [They] craved fame and fortune and deliberately went against the country's regulations on scientific research and medical management. [They] went beyond the bottom lines of scientific research and medical ethics," the court stated, according to the South China Morning Post.

He has defended his controversial work by saying that it will help families. "I understand my work will be controversial," he said, as NPR's Rob Stein reported. "But I believe families need this technology. And I am willing to take the criticism for them."

At the time, scientists had previously genetically modified human embryos, but none had publicly claimed to have implanted embryos in a woman's womb in an experiment that resulted in human babies.

Chinese police detained He in January and, as the Post reported, an initial investigation concluded that he "organised a project team that included foreign staff, which intentionally avoided surveillance and used technology of uncertain safety and effectiveness to perform human embryo gene-editing activity with the purpose of reproduction, which is officially banned in the country."

The gene that He edited, CCR5, is known as a pathway for HIV to infect immune system cells. But as Stein notes, research carried out since He's stunning announcement has suggested that the genetic changes he made could cause more harm than good to the babies' health.

A study in Nature Medicine analyzed the DNA of more than 400,000 people and found that the changes that He made could make people more vulnerable to viruses such as West Nile and influenza.

"This is a lesson in humility," George Daley, the dean of the Harvard Medical School, told Stein. "Even when we think we know something about a gene, we can always be surprised and even startled, like in this case, to find out that a gene we thought was protective may actually be a problem."

Marcy Darnovsky, the executive director of the Center for Genetics and Society, said in an email to NPR that He's "reckless and self-serving acts should highlight the broader and deeper risks and the pointlessness of any proposal to use gene editing in human reproduction."

William Hurlbut, a scientist and bioethicist at Stanford who had attempted to persuade He (who is nicknamed JK) not to do the experiment, called his arrest a "sad story."

"Everyone lost in this (JK, his family, his colleagues, and his country), but the one gain is that the world is awakened to the seriousness of our advancing genetic technologies," Hurlbut said in an emailed statement. "I feel sorry for JK's little family though I warned him things could end this way, but it was just too late."

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Chinese Researcher Who Created Gene-Edited Babies Sentenced To 3 Years In Prison - NPR


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