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DUBLIN, Feb. 7, 2020 /PRNewswire/ -- The "Molecular Diagnostics Global Market - Forecast to 2026" report has been added to ResearchAndMarkets.com's offering.

The global molecular diagnostics global market is estimated to reach $18,668.9 million by 2026 growing at a high single-digit CAGR from 2019 to 2026.

Among the overall molecular diagnostic market is increasing prevalence of different types of cancers, infectious diseases, genetic disorders and other diseases, increasing awareness in personalized medicine and companion diagnostics and also growth in the point of care testing and sequencing-based tests and other molecular techniques.

Molecular diagnostics plays a pivotal role in the evaluation of the disease and for the effective response for specific therapy. However, the complex regulations for the approval of molecular diagnostic tests, availability of competing/alternative technologies, high cost of the tests, and also a shortage of technical experts are some of the restrains for the growth of the molecular diagnostics market.

Segment Highlights

The molecular diagnostics global market is segmented based on product, technology, application and end-users.

The product market is further categorized into instruments, consumables and software and services. As per research estimations, the consumable global market commanded the largest revenue in 2019 and is projected to grow at double-digit CAGR from 2019 to 2026.

The molecular diagnostics global market by technology is divided into PCR, microarray and microfluidics, isothermal nucleic acid amplification tests, in-situ hybridization, NGS and other technologies. PCR accounted for the largest revenue in 2019 and is expected to grow at a double-digit CAGR from 2019 to 2026 due to low cost and is a common and indispensable technique used for diagnosis when compared to other instruments such as NGS and also due to technological advancements in PCR and their subtypes such as digital droplet PCR with precise and highly sensible results.

The molecular diagnostics by application market is classified into infectious diseases, oncology, genetic testing, transplantation, blood screening and other diseases such as metabolic disorders and diseases associated with the central nervous system. The largest revenue was contributed by infectious diseases segment in 2019 and this market is expected to grow at a high single-digit CAGR from 2019 to 2026 due to high incidence of bacterial and viral infections.

Infectious diseases are further segmented into bacterial, viral and other diseases. The viral diseases commanded the largest revenue in 2019 and the market is expected to grow at a strong double-digit CAGR from 2019 to 2026. Viral diseases are further segmented into HIV, hepatitis, HPV, influenza and other viral infections. Among these, HIV accounted for the largest revenue in 2019 and is expected to grow at a double-digit CAGR from 2019 to 2026.

The bacterial diseases are sub-segmented into sexually transmitted diseases (STD) caused by bacteria, hospital acquired infections, tuberculosis and other diseases such as sepsis, pneumonia and meningitis, etc. Sexually transmitted disease accounted for the largest revenue in 2019 and is expected to grow at high single-digit CAGR from 2019 to 2026. The growth is attributed to the increased awareness about the molecular based kits available for the diagnoses of STDs and also increases in the prevalence.

Under genetic testing segment the market is segmented into NIPT, cystic fibrosis and other genetic testing, among them NIPT commanded the largest revenue in 2019 and is expected to grow at a double digit CAGR from 2019 to 2026 as NIPT provides a safer alternative to invasive tests and it analyzes fetal cell-free DNA (cfDNA) from the mother's circulation, making early detection of genetic disorders such as Down syndrome and other chromosomal aberrations easier.

Based on the type of cancer, the oncology market is segmented into lung, breast, colorectal, prostate, ovarian, melanoma, ovarian and other cancers. The largest revenue under oncology was accounted for by colorectal cancer with the revenue in 2019 and breast cancer is expected to grow at double-digit CAGR from 2019 to 2026.

Based on the cancer care, the oncology segment is subdivided into early screening, companion diagnostics, prognosis and recurrence. Early screening contributed for the largest revenue in 2019 and companion diagnostics is expected to grow at double-digit CAGR from 2019 to 2026. Further, the transplantation market is segmented into kidney, heart and other transplantation such as lung and pancreatic transplantation. Among them, kidney transplantation commanded the largest revenue in 2019.

Molecular diagnostics end-users market is segmented into hospitals, clinical/centralized laboratories, academics and research and other end users. Clinical/centralized laboratories accounted for the largest revenue due to the rapid adoption of technology and economies of scale in testing a large number of samples collected from affiliated hospitals.

Geographical wise, North America region commanded the largest revenue in 2019 and is expected to grow at a mid-single-digit CAGR from 2019 to 2026 owing to the high demand for early detection, treatment selection and prevention of diseases with advanced technology due to diseases associated with the lifestyle. However, the Asia-pacific region is expected to grow at an early teen CAGR from 2019 to 2026 attributing to increasing awareness of the molecular based test for the better outcome.

Competitive Landscape

The molecular diagnostics global market is a competitive market and all the existing players in this market are involved in developing new and advanced molecular based techniques for diagnosis to maintain their market shares and also acquiring companies for product expansion.

Some of the key players in molecular diagnostics global market are Abbott Laboratories (U.S.), F.Hoffmann-LA Roche AG (Switzerland), BioMerieux (France), Qiagen (Netherlands) Exact Sciences (U.S.), Grifols (Spain), Danaher Corporation (U.S.), Hologic, Inc. (U.S.), and Myriad Genetics, Inc. (U.S.)

Key Topics Covered

1 Executive Summary

2 Introduction

3 Market Analysis3.1 Introduction3.2 Market Segmentation3.3 Factors Influencing Market3.3.1 Drivers and Opportunity3.3.1.1 Increasing Incidence of Infectious Diseases3.3.1.2 Rising Incidence of Cancer and Non-Infectious Diseases3.3.1.3 Technological Advancements3.3.1.4 Favorable Reimbursements3.3.1.5 Investment by Major Players3.3.2 Restraints and Threats3.3.2.1 Lack of Skilled Professionals3.3.2.2 High Cost of Molecular Diagnostics Products3.3.2.3 Lack of Standardization of the Molecular Diagnostics Test3.3.2.4 Stringent and Time-Consuming Regulatory Issues3.3.2.5 Lack of Reproducibility and Repeatability3.3.2.6 Biochemical and Alternative Tests3.4 Market Share Analysis3.4.1 Molecular Diagnostics Global Market Share Analysis3.4.2 Molecular Diagnostics In Infectious Diseases Market Share3.5 Regulatory Affairs3.5.1 U.S.3.5.2 Europe3.5.3 China3.5.4 India3.5.5 Japan3.5.6 Australia3.5.7 South Korea3.6 Reimbursement Scenario3.7 Clinical Trials3.7.1 Ctdna Clinical Trials3.7.2 Cfdna Clinical Trials3.7.3 Circulating Tumor Cells3.7.4 Companion Diagnostics3.8 Latest and Upcoming Products3.9 Porter's Five Force Analysis3.10 Funding Scenario

4 Market Sizing4.1 U.S.Cancer Care Market Sizing Information4.1.1 Oncology Testing4.1.1.1 Early Screening4.1.1.2 Companion Diagnostics4.1.1.3 Prognosis Monitoring4.1.1.4 Recurrence Monitoring4.1.2 Non-Invasive Prenatal Screening (NIPT)4.1.3 Transplantation Diagnostics

5 Molecular Diagnostics Global Market, by Products5.1 Introduction5.2 Instruments5.3 Consumables5.4 Software and Services

6 Molecular Diagnostics Global Market by Technology6.1 Introduction6.2 PCR6.3 Microfluidics and Microarray6.4 Isothermal Nucleic Acid Amplification Technology (INAAT)6.5 In-Situ Hybridization6.6 Next Generation Sequencing (NGS)6.7 Others

7 Molecular Diagnostics Global Market, by Application7.1 Introduction7.2 Infectious Diseases7.2.1 Bacterial Diseases7.2.1.1 Sexually Transmitted Diseases7.2.1.2 Hospital Acquired Infections7.2.1.3 Tuberculosis7.2.1.4 Others7.2.2 Viral Diseases7.2.2.1 Hiv7.2.2.2 Hepatitis7.2.2.3 Influenza7.2.2.4 Human Papiloma Virus (HPV)7.2.2.5 Other Viral Diseases7.2.3 Other Infectious Diseases7.3 Genetic Testing7.3.1 Non-Invasive Prenatal Testing (NIPT)7.3.2 Cystic Fibrosis7.3.3 Other Genetic Diseases7.4 Oncology Testing7.4.1 Cancer Types7.4.1.1 Introduction7.4.1.2 Lung Cancer7.4.1.3 Breast Cancer7.4.1.4 Colorectal Cancer7.4.1.5 Prostate Cancer7.4.1.6 Melanoma7.4.1.7 Ovarian Cancer7.4.1.8 Others7.4.2 Cancer Care7.4.2.1 Introduction7.4.2.2 Early Screening7.4.2.3 Companion Diagnostics7.4.2.4 Prognosis Monitoring7.4.2.5 Recurrence Monitoring7.5 Transplantation7.5.1 Kidney Transplantation7.5.2 Heart Transplantation7.5.3 Other Transplantation7.6 Blood Screening7.7 Other Diseases

8 Molecular Diagnostics Global Market, by End Users8.1 Introduction8.2 Hospitals8.3 Clinical/Centralized Laboratories8.4 Academic and Research8.5 Others

9 Molecular Diagnostics Global Market, by Region9.1 Introduction9.2 North America9.2.1 U.S.9.2.2 Rest of North America9.3 Europe9.3.1 France9.3.2 Germany9.3.3 Italy9.3.4 Rest of Europe9.4 Asia-Pacific Region9.4.1 China9.4.2 India9.4.3 Japan9.4.4 Rest of Asia-Pacific9.5 Rest of the World9.5.1 Brazil9.5.2 Rest of Latin America9.5.3 Middle East and Others

10 Competitive Landscape10.1 Introduction10.2 Approvals10.3 Collaborations10.4 Acquisitions10.5 New Product Launches10.6 Others

11 Major Companies11.1 Abbott Laboratories11.1.1 Overview11.1.2 Financials11.1.3 Product Portfolio11.1.4 Key Developments11.1.5 Business Strategy11.1.6 SWOT Analysis11.2 Becton, Dickinson and Company11.3 BioMerieux11.4 Danaher Corporation11.5 Exact Sciences Corporation11.6 Grifols, S.A.11.7 Hologic, Inc.11.8 Myriad Genetics, Inc.11.9 Qiagen N.V.11.10 F. Hoffmann-La Roche Ltd.

Companies Mentioned

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Molecular Diagnostics Industry Report, 2020 to 2026 - Analysis by Product, Technology, Application, End-user and Region - PRNewswire

Like most medical students, I struggled to memorize the Krebs cycle, the complex energy-producing process that takes place in the body's mitochondria. Rote learning of Sir Hans Krebs' eponymous cascade of reactions persists and has been cited as a waste of time in modern medical education. However, it looks like that specialized knowledge about mitochondrial structure and function may finally come in handy in the clinic.

Advances in genetics have contributed to improved diagnostic accuracy of a diverse spectrum of mitochondrial disorders. Respiratory chain, nuclear gene, and mitochondrial proteome mutations can lead to multisystem or organ-specific dysfunction.

A new potential treatment for mitochondrial disorders, elamipretide, has received orphan drug designation from the US Food and Drug Administration (FDA) and is in clinical trials sponsored by Stealth Biotherapeutics. [Dr Wilner has consulted for Stealth Biotherapeutics.] Recently I had the opportunity to interview Hilary Vernon, MD, PhD, associate professor of genetic medicine at Johns Hopkins University, Baltimore, Maryland, and an expert on mitochondrial disorders. Dr Vernon discussed her research on elamipretide as a treatment for Barth syndrome, a rare form of mitochondrial disease.

I am the director of the Mitochondrial Medicine Center at Johns Hopkins Hospital. I work with individuals from infancy through adulthood who have mitochondrial conditions. I became interested in this particular area when I was early in my pediatrics/genetics residency at Johns Hopkins and saw the toll that mitochondrial disorders took on patients' lives and the limited effective therapies. At that point, I decided to focus on patient care and research in this area.

Mitochondrial disorders can be difficult to recognize because of their inherent multisystem nature and variable presentations (even between affected members of the same family). However, there are several considerations that should raise a clinician's suspicion for a mitochondrial condition. Ascertaining a family history of disease inheritance through the maternal line can raise the suspicion for a mitochondrial DNA disorder. Identification of a combination of medical issues in different organ systems that are seemingly unrelated in an individual (ie, optic atrophy and muscle weakness or diabetes and hearing loss) can also raise suspicion for a mitochondrial condition.

Due to the nature of mitochondria as the major energy producers of the cells, high-energy-requiring tissues such as the brain and the muscles are often affected. Perhaps the best known mitochondrial diseases to neurologists are MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke) as well as MERFF (myoclonic epilepsy with ragged red fibers). There is a nice body of literature on the effects of arginine and citrulline in modifying stroke-like episodes in MELAS, and this is a therapy that is in current practice.

Mitochondria are complex organelles whose structure and function are encoded in hundreds of genes originating from both the nucleus of the cell and the mitochondria themselves. Mitochondria have many key roles in cellular function, including energy production through the respiratory chain, coordination of apoptosis, nitrogen metabolism, fatty acid oxidation, and much more.

Various cofactors and vitamins can be employed to improve mitochondrial function for different reasons. For example, if a specific enzyme is dysfunctional, supplying the cofactor for that enzyme may improve its function (ie, pyruvate dehydrogenase and thiamine). Antioxidants have also been considered to help reduce the oxidant load that could potentially cause ongoing damage to the mitochondrial membrane resulting from respiratory chain dysfunction (ie, coenzyme Q-10).

It is important to remember that the highest number of individual mitochondrial disorders result from mutations in genes located in the nuclear DNA. For example, the TAZ gene that is abnormal in Barth syndrome is a nuclear gene located on the X chromosome. These genes are amenable to the "regular" approaches to gene therapy.

Targeting mitochondrial DNA for gene therapy requires a different set of approaches because the gene delivery has to overcome the barrier of the mitochondrial membranes. However, research is ongoing to overcome these obstacles.

Barth syndrome is a very rare genetic X-linked disorder that usually only affects males. The genetic defect leads to an abnormal composition of cardiolipin on the inner mitochondrial membrane. Cardiolipin is an important phospholipid involved in many mitochondrial functions, including organization of inner mitochondrial membrane cristae, involvement in apoptosis, and organization of the respiratory chain (which is responsible for producing ATP via the process of oxidative phosphorylation), and many of these functions are abnormal in Barth syndrome. Individuals with Barth syndrome typically have early-onset cardiomyopathy, myopathy, intermittent neutropenia, fatigue, poor early growth, among other health concerns.

Early in my post-residency career, I followed several patients with Barth syndrome and was quickly welcomed into the Barth syndrome community by the families and the Barth Syndrome Foundation. From there, I founded the only interdisciplinary Barth syndrome clinic in the US and began to focus a significant amount of my clinical and laboratory research on this condition.

Most commonly, these individuals come to medical attention because of cardiomyopathy, but a minority of patients do come to attention due to repeated infections and neutropenia. Patients were identified for study participation through the Barth Syndrome Foundation or because they were already patients of my study team.

All participants were known to have Barth syndrome prior to study entry, and all had confirmatory genetic testing showing a pathogenic mutation in the TAZ gene.

By binding to cardiolipin in the inner mitochondrial membrane, elamipretide is believed to stabilize cristae architecture and electron transport chain structure during oxidative stress. I thought it would be great if this could help to stabilize the abnormal cardiolipin components on the inner mitochondrial membrane in Barth syndrome.

We observed improvements in several areas across the study population in the open-label extension part of the study. This includes a significant improvement in exercise performance (as measured by the 6-minute walk test, with an average improvement of 95.9 meters at 36 weeks) and a significant improvement in muscle strength. We also observed a potential improvement in cardiac stroke volume. Most of the adverse events were local injection-site reactions and were mild to moderate in nature.

The TAZPOWER trial has an ongoing open-label extension with the same endpoints as the placebo-controlled portion evaluated on an ongoing basis. In addition, in my laboratory, we are using induced pluripotent stem cells to learn more about how cardiolipin abnormalities affect different cell types in an effort to understand the tissue specificity of disease. This will help us to understand whether different aspects of Barth syndrome would necessitate individual management or clinical monitoring strategies.

Mitochondrial inner membrane dysfunction is increasingly recognized as a major aspect of the pathology of a wide range of mitochondrial conditions. Therefore, based on the role of stabilizing mitochondrial membrane components, elamipretide has a potential role in many disorders of the mitochondria.

Yes, this is what we would call "secondary mitochondrial dysfunction" (meant to differentiate from "primary mitochondrial disease," which is caused by defects in genes that encode for mitochondrial structure and function). Approaches intended to protect the mitochondria from further damage, such as antioxidants or strategies that can bypass the mitochondria for ATP production, could overlap as treatment for primary mitochondrial disease and secondary mitochondrial dysfunction.

This is something that is much discussed as a newer consideration for families who are affected by disorders of the mitochondrial DNA, but not something I have experience with firsthand.

Yes. The United Mitochondrial Disease Foundation and the Mitochondrial Medicine Society collaborated to develop the Mito Care Network, with 19 sites identified as Mitochondrial Medicine Centers across the US.

Andrew Wilner is an associate professor of neurology at the University of Tennessee Health Science Center in Memphis, a health journalist, and an avid SCUBA diver. His latest book is The Locum Life: A Physician's Guide to Locum Tenens.

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Read more:
Maybe Memorizing the Krebs Cycle Was Worthwhile After All - Medscape

This article is part of the Technology Insight series, made possible with funding from Intel.

When my son was a toddler, he went to his pediatrician for a routine CAT scan. Easy stuff. Just a little shot to subdue him for a few minutes. Hed be awake and finished in a jiffy.

Except my son didnt wake up. He lay there on the clinic table, unresponsive, his vitals slowly falling. The clinic had no ability to diagnose his condition. Five minutes later, he was in the back of an ambulance. My wife and I were powerless to do anything but look on, frantic with worry for our boys life.

It turned out that hed had a bad reaction to a common hydrochloride sedative. Once that was figured out, doctors quickly brought him back around, and he was fine.

But what if, through groundbreaking mixtures of compute, database, and AI technologies, a quick round of analyses on his blood and genome could have revealed his potential for such a reaction before it became a critical issue?

What if it were possible to devise a course of treatment specific to him and his bodys unique conditions, rather than accepting a cookie-cutter approach and dealing with the ill effects immediately after?

And what if that could be done with small, even portable medical devices equipped with high-bandwidth connectivity to larger resources?

In short, what if, through the power of superior computing and next-generation wireless connectivity, millions of people like my son could be quickly, accurately treated on-site rather than endure the cost and trauma of legacy medical methods?

These questions I asked about my son are at the heart of todays efforts in precision medicine. Its the practice of crafting treatments tailored to individuals based on their characteristics. Precision medicine spans an increasing number of fields, including oncology, immunology, psychiatry, and respiratory disorders, and its back end is filled with big data analytics.

Key Points:

Pairing drugs to gene characteristics only covers a fraction of the types of data that can be pooled to target specific patient care.

Consider the Montefiore Health System in the Bronx. It has deployed a semantic data lake, an architecture for collecting large, disparate volumes of data and collating them into usable forms with the help of AI. Besides the wide range of data specific to patients collected onsite (including from a host of medical sensors and devices), Montefiore healthcare professionals also collate data from sources as needed, including PharmGKB databank (genetic variations and drug responses), the National Institute of Healths Unified Medical Language System (UMLS), and the Online Mendelian Inheritance in Man (human genomic data).

Long story short, the Intel/Cloudera/Franz-based solution proved able to accurately create risk scores for patients, predict whether they would have a critical respiratory event, and advise doctors on what actions to take.

We are using information for the most critically ill patients in the institution to try and identify those at risk of developing respiratory failure (so) we can change the trajectory, noted Dr. Andrew Racine, Montefiores system SVP and chief medical officer.

Now that institutions like Montefiore can perform AI-driven analytics across many databases, the next step may be to integrate off-site communications via 5G networking. Doing so will enable physicians to contribute data from the field, from emergency sites to routine in-home visits, and receive real-time advice on how to proceed. Not only can this enable healthcare professionals to deliver faster, more accurate diagnoses, it may permit general physicians to offer specialized advice tailored to a specific patients individual needs. Enabling caregivers like this with guidance from afar is critical in a world that, researchers say, faces a shortage 15 million healthcare workers by 2030.

Enabling services like these is not trivial in any way. Consider the millions of people who might need to be genetically sequenced in order to arrive at a broad enough sample population for such diagnostics. Thats only the beginning. Different databases must be combined, often over immense distances via the cloud, without sacrificing patients rights or privacy. Despite the clear need for this, according to the Wall Street Journal, only 4% of U.S. cancer patients in clinical trials have their genomic data made available for research, leaving most treatment outcomes unknown to the research and diagnostic communities. New methods of preserving patient anonymity and data security across systems and databases should go a long way toward remedying this.

One promising example: using the processing efficiencies of Intel Xeon platforms in handling the transparent data encryption (TDE) of Epic EHR patient information with Oracle Database. Advocates say the more encryption and trusted execution technologies, such as SGX, can be integrated from medical edge devices to core data centers, the more the public will learn to allow its data to be collected and used.

Beyond security, precision medicine demands exceptional compute power. Molecular modeling and simulations must be run to assess how a drug interacts with particular patient groups, and then perhaps run again to see how that drug performs the same actions in the presence of other drugs. Such testing is why it can take billions of dollars and over a decade to bring a single drug to market.

Fortunately, many groups are employing new technologies to radically accelerate this process. Artificial intelligence plays a key role in accelerating and improving the repetitive, rote operations involved in many healthcare and life sciences tasks.

Pharmaceuticals titan Novartis, for example, uses deep neural network (DNN) technology to accelerate high-content screening, which is the analysis of cellular-level images to determine how they would react when exposed to varying genetic or chemical interactions. By updating the processing platform to the latest Xeon generation, parallelizing the workload, and using tools like the Intel Data Analytics Acceleration Library (DAAL) and Intel Caffe, Novartis realized nearly a 22x performance improvement compared to the prior configuration. These are the sorts of benefits healthcare organizations can expect from updating legacy processes with platforms optimized for acceleration through AI and high levels of parallelization.

Interestingly, such order-of-magnitude leaps in capability, while essential for taming the torrents of data flowing into medical databases, can also be applied to medical IoT devices. Think about X-ray machines. Theyre basically cameras that require human specialists (radiologists) to review images and look for patterns of health or malady before passing findings to doctors. According to GE Healthcare, hospitals now generate 50 petabytes of data annually. A staggering 90% comes from medical imaging, GE says, with more than 97% unanalyzed or unused. Beyond working to use AI to help reduce the massive volume of reject images, and thus cut reduce on multiple fronts, GE Healthcare teamed with Intel to create an X-ray system able to capture images and detect a collapsed lung (pneumothorax) within seconds.

Simply being able to detect pneumothorax incidents with AI represents a huge leap. However, part of the projects objective was to deliver accurate results more quickly and so help to automate part of the diagnostic workload jamming up so many radiology departments. Intel helped to integrate its OpenVINO toolkit, which enables development of applications that emulate human vision and visual pattern recognition. Those workloads can then be adapted for processing across CPUs, GPU, AI-specific accelerators and other processors.

With the optimization, the GE X-ray system performed inferences (image assessments) 3.3x faster than without. Completion time was less than one second per image dramatically faster than highly trained radiologists. And, as shown in the image above, GEs Optima XR240amx X-ray system is portable. So this IoT device can deliver results from a wide range of places and send results directly to doctors devices in real time over fast connections, such as 5G. A future version could feed analyzed X-rays straight into patient records. There, they become another factor in the multivariate pool that constitutes the patients dataset, which in turn, enables personalized recommendations by doctors.

By now, you see the problem/solution pattern:

The U.S. provides a solid illustration of the impact of population in this progression. According to the U.S. Centers for Disease Control (CDC), even though the rate of new cancer incidents has flattened in the last several years, the countrys rising population pushed the number of new cases diagnosed from 1.5 million in 2010 to 1.9 million in 2020, driven in part by rising rates in overweight, obesity, and infections.

The white paper Accelerating Clinical Genomics to Transform Cancer Care (below) paints a stark picture of the durations involved in traditional approaches to handling new cancer cases from initial patient visit to data-driven treatment.

At each step, delays plague the process extending patient anxiety, increasing pain, even leading to unnecessary death.

Intel created an initiative called All in One Day to create a goal for the medical industry: take a patient from initial scan(s) to precision medicine-based actions for remediation in only 24 hours. This includes genetic sequencing, analysis that yields insights into the cellular- and molecular-level pathways involved in the cancer, and identification of gene-targeted drugs able to deliver the safest, most effective remedy possible.

To make All in One Day possible, the industry will require secure, broadly trusted methods for regularly exchanging petabytes of data. (Intel notes that a typical genetic sequence creates roughly 1TB of data. Now, multiply that across the thousands of genome sequences involved in many genomic analysis operations.) The crunching of these giant data sets calls for AI and computational horsepower beyond what todays massively parallel accelerators can do. But the performance is coming.

As doctors will have to service ever-larger patient populations, expect them to need data results and visualizations delivered to wherever they may be, including in forms animated or rendered in virtual reality. This will require 5G-type wireless connectivity to facilitate sufficient data bandwidth to whatever medical IoT devices are being used.

If successful, more people will get more personalized help and relief than ever possible. The medical IoT and 5G dovetail with other trends now reshaping modern medicine and making these visions everyday reality. A 2018 Intel survey showed that 37% of healthcare industry respondents already use AI; the number should rise to 54% by 2023. Promising new products and approaches appear daily. A few recent examples are here, here and here.

As AI adoption continues and pairs with faster hardware, more diverse medical devices, and faster connectivity, perhaps we will soon reach a time when no parent ever has to watch an unresponsive child whisked away by ambulance because of adverse reactions that might have been avoided through precision medicine and next-gen technology.

More here:
AI, 5G, and IoT can help deliver the promise of precision medicine - VentureBeat

The lottery that began this week was not about money, or about choosing a school, or about obtaining a visa. It was about a childs life.

In this case, the children selected would receive a drug that otherwise was not available. Jamie Clarkson, an electrician in Queensland, Australia, entered his 18-month-old daughter, Wynter.

We applied for it because we desperately want this drug for our daughter, but youre putting your daughters well-being and longevity in the hands of a lottery, Clarkson said. I guess its the fairest way to decide who gets the drug and who doesnt, but yeah, its not a great feeling.

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The treatment, a gene therapy called Zolgensma, is designed for children like Wynter who have a neuromuscular disease called spinal muscular atrophy, or SMA. Without it or other treatments, those with the most serious type are likely to die as babies. It was first approved by U.S. regulators only last year, and is not yet available in other countries.

The lottery was devised by the drugs manufacturer, Novartis, to give families in those places a chance to get it through a novel form of compassionate use a way to get medications that have not been approved while they wait. Fifty doses are slotted to be given away for free in the first half of the year, with up to 100 total.

The first drawing occurred Monday.

Ethicists and advocates have debated the merits and the design of the unusual arrangement. Parents said that it was uncomfortable to cast their childs fate into what felt like a sweepstakes a kind of bizarre Willy Wonka contest in which, as Maura Blair, a Canadian mother of a child with SMA put it, were talking about lives. But if it was a chance to get the drug, it was worth trying.

Zolgensma costs $2.1 million in the United States the worlds most expensive drug. And even if it is to cost less in other countries, even if it is to be covered by insurance, infants at this point are not eligible for it after turning 2. Some families have even tried to fundraise in hopes of buying the drug themselves and getting it injected by doctors in the United States.

Shes 7 months, Laura Silva, who lives north of Toronto, said about her daughter, Rebecca. Do we rely on their word and wait it out? Or do we take action ourselves? Because the sooner she can get it, the better for her.

Some parents said they had taken issue with news coverage of the lottery, which has framed the eventual recipients of the drugs as lucky winners. If that were the case, what did that say about everyone else?

The kids appeared healthy at birth. But soon, their parents recalled, it became clear that something was wrong. They couldnt raise or control their arms and legs. They would choke on their milk.

Jamie Clarkson, in Australia, said he and his wife, Kellee, had a friend with a daughter around Wynters age. When laid face down (tummy time, in parental parlance), the girl had no problem lifting her head.

The difference was chalk and cheese, he said. Our girl sort of laid there and didnt do anything.

Sometimes the parents were told their kids just needed more time, but eventually, a clinical evaluation and genetic test would confirm the SMA diagnosis. The most serious form, called type 1, is estimated to affect 1 in 15,000 babies.

Children with the disease have a mutation in a gene called SMN1 (or a missing gene) that meant cells dont produce sufficient SMN protein. The dearth of the protein debilitates motor neurons, which are responsible for relaying messages to muscles, and creates a cascade of issues that culminates in muscle weakness.

Without treatment, babies with type 1 SMA might never be able to lift their heads or arms or legs, and struggle to regulate their swallowing and breathing. Most die by 2, typically because of respiratory issues.

Zolgensma works by ferrying a healthy copy of an SMN gene into motor neurons restoring production of the protein and the health of the neurons. It is a one-time treatment with lasting benefits like reigniting a pilot light.

When Zolgensma won approval from the U.S. Food and Drug Administration in May, it was hailed a monumental victory for families and an achievement in genetic medicine one of the first gene therapies to make it to the market. But it also created a divide between haves and have-nots American parents, assuming insurance companies would cover the treatment, and parents anywhere else in the world.

It is not uncommon for a drug to be available in the United States before other countries; drug makers routinely apply for and receive regulatory clearance from agencies around the world at different times. But the FDAs approval drove global appeals for a drug that offered babies a chance.

Beyond the issue of regulatory approval, supplies of Zolgensma are tight, Novartis has said. Gene therapies are complex to manufacture, and the company only has one facility producing the drug right now, with plans for two more to come online this year. It also needs to have doses available for U.S. patients and for patients in other countries where the drug could become available in the coming months. (European regulators are expected to decide on Zolgensma this quarter, and Japanese officials before the middle of the year, the company has said. Decisions in Canada and Australia may not come until 2021.)

Novartis saw a lottery as the answer.

Random lotteries are an accepted way to mete out resources when there is a limited amount, some ethicists have argued. They establish an equal playing field and remove the possibility that those with money or connections can maneuver to jump the line.

But experts have also questioned whether Novartis has done enough to try to overcome the scarcity issues. Some have also said that favoring those with the greatest need meaning the sickest children would be a more ethical approach; patients who are healthier could potentially wait until the drug is approved in their home countries or until more supply is available.

If it is really not possible to help all who are in need of help, then a lottery with priority to patients who are worst off is not a bad approach and definitely fairer than other things a company could do, said Holly Fernandez Lynch, a bioethicist at University of Pennsylvanias Perelman School of Medicine. The key is to first do everything possible to minimize the need for a lottery at all and its not obvious to me that Novartis has done that here.

The fact that the lottery created a situation in which there are, for lack of better descriptors, winners and losers also left some people uneasy.

You cant do anything to improve your chances, said Genevieve Kanter, also a bioethicist at Penn. But it does become a zero-sum game, which is what bothers some people about the mechanism, even if at the end of the day, more kids get treated than in the alternate scenario where theres no lottery.

Its the price we have to pay to have some kids treated.

In an interview with STAT, the president of AveXis, the Novartis unit that developed Zolgensma, said the company considered prioritizing the patients who were sickest or those for whom another SMA treatment did not help. But the company, which is using an outside party to handle the selection and brought in ethicists to consult on the system, did not want to put a finger on the scale in any way, he said. Instead, selections would be random.

Its the only fair way to allocate, the official, Dave Lennon, said, even as he acknowledged, its not an ideal situation.

The alternative is not do anything, which we didnt feel like was a good option, he added.

He said if the supply was sufficient, Novartis hoped to expand the program.

Novartis would not say how many people were being selected each time. Drawings are set to take place every two weeks.

And that means families in desperate need have a chance to obtain the medicine just as often.

For them, they try every possible way to get this Zolgensma, said Csilla Galik, a friend of the family of Noel lys, who has type 1 SMA and whose family lives in Romania near the Hungarian border. They need to try every possibility because this medicines price is incredible.

Beyond Zolgensma, there is another treatment for SMA: Spinraza, manufactured by the drug maker Biogen and more widely available globally. Injected into the spinal fluid every few weeks and then every four months, it promotes the production of the SMN protein by boosting the activity of another gene similar to SMN1.

Many of the children waiting for Zolgensma are already receiving Spinraza, and their parents say it appears to be helping, to an extent.

Wynter Clarksons motor function has improved, though not as much as her parents had hoped it would. She can move her head and raise her arms, and can sit up with a back brace. She can rock from side to side, but not quite roll over. Each treatment requires the family to travel about two and a half hours from their home in Toowoomba to Brisbane.

Spinraza and Zolgensma have not been compared in a head-to-head study, and how long the benefits of Zolgensma last is not yet known. But parents said they see a one-time infusion of Zolgensma which replaces the faulty gene at the root of the disease, instead of just building a workaround as the best option for their children.

Even when children are on Spinraza, their disease can progress, if at a slower rate, parents said.

Blair said her daughter, Lennon, has more control over her head and limbs since starting Spinraza. But after three doses, the girl still needed a feeding tube inserted; she lost her ability to swallow. Thats on top of other care required by Blair and other parents of infants with the disease. Oxygen levels needed to be checked, sleeping sometimes requires a mask and machines to aid breathing, physical therapy exercises are done to try to coax some muscle activity.

You basically repeat that all day, all day until bed time, said Blair, of St. Catharines, Ontario. And everything takes so long.

There is another wrinkle to having a child with the disease: Its inherited, and some parents though not all said they felt responsible for having passed on a mutation that made their child so sick.

To have the disease, a child needs to inherit two mutated copies of the gene, one from each parent who can go through life not knowing they are carrying the mutation until they have a child with the disease.

The parents who have struggled with a sense of guilt know they shouldnt blame themselves, but they still catch themselves wondering if there was something they could have done differently.

Its something we technically gave to her, not even knowing that we could, said Laura Silva, the mother who lives near Toronto. And thats the hardest part.

When it came time for the lottery drawing this week, her daughter Rebeccas name wasnt in the pool she hadnt yet gotten the necessary approval from a Candian health authority to try an experimental drug. Its not clear how many Canadian children found themselves in similar circumstances, or how many were successfully entered by their doctors. Some parents said they were still waiting for that approval.

Noel, the boy in Romania, was entered by his doctor. But his family had not heard anything following the initial drawing. Neither had the Clarksons in Australia:

No word from our neurologist about the free Zolgensma dose, Jamie wrote in an email Tuesday, so Im assuming Wynter wasnt picked this time around, unfortunately.

Winnie Luk-Taylor and Cory Taylor, who live outside Toronto, were once hopeful that Zolgensma could help their daughter, Skye.

She was born in June. Her motor skills werent developing as they should have, and her breath had a rattle to it, as if she were congested. At around 4 months, Skye was diagnosed with SMA and, with a cough, her parents were told to take her to the hospital. She was also started on Spinraza.

She spent a month and a half at the hospital with respiratory infections and complications. She died Dec. 21.

Skye took it all in and smiled at every one and didnt seem to realize she was experiencing some very, I guess, major medical procedures, her mom said. She was a very good-natured girl.

Luk-Taylor said she sometimes wondered what might have happened if Skye had been born one year later June 24, 2020, not 2019. Ontario, the province where they live, started testing for SMA this year as part of its newborn screening, meaning Skye might have been diagnosed earlier in her life and started on Spinraza sooner. Maybe it could have had more of an effect. And maybe Zolgensma would have become available to Canadian babies not long after that.

Instead, at Christmas, Luk-Taylor wrote her daughter a poem.

We will never let you go, it reads in part.

Your spirit will live onIt lives in everything I doI will always fight for youI will always care for youI will always dream of youI got to see who you were to becomeAnd I am blessed and proud of youI am blessed and proud of youI hope you see and hear me nowAnd know that I love you.

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Lottery like no other offers a cutting-edge medicine with lives on the line - STAT

WALTHAM, Mass.--(BUSINESS WIRE)--Dyne Therapeutics, a biotechnology company pioneering targeted therapies for patients with serious muscle diseases, today announced the addition of three key members to its leadership team: Oxana Beskrovnaya, Ph.D., senior vice president and head of research; Chris Mix, M.D., senior vice president, clinical development; and John Najim, vice president, chemistry, manufacturing and controls (CMC).

Dyne is establishing a leadership position in muscle disease therapeutics by combining transformative science with an organizational passion for changing the lives of patients, said Joshua Brumm, president and chief executive officer of Dyne. We are thrilled to welcome Oxana, Chris and John to our growing team. Leveraging their collective experience in the discovery and development of novel medicines, we are poised to rapidly advance our programs toward the clinic and are fully focused on execution.

Dr. Beskrovnaya is an accomplished R&D leader with a strong track record of discovering and developing first-in-class therapeutics for rare genetic diseases. Prior to joining Dyne, she served as head of musculoskeletal and renal research in Sanofis rare disease and neurological unit, where she advanced a pipeline of drug candidates using multiple therapeutic modalities, including nucleic acids, proteins and small molecules. Dr. Beskrovnaya is the author of numerous patents, invited reviews, editorials, book chapters and original research articles in major scientific journals. She received her Ph.D. in genetics from Moscow Genetics Institute, followed by postdoctoral fellowship training in neuromuscular diseases at the Howard Hughes Medical Institute at the University of Iowa.

Dr. Mix brings extensive clinical development experience to Dyne, most recently serving as vice president of rare genetic disease clinical development at Agios Pharmaceuticals, where he oversaw development across several hemolytic anemia indications. In his previous role as vice president of clinical development at Sarepta Therapeutics, he focused on advancing candidate therapies for rare neuromuscular disease. Dr. Mix received his B.A. in chemistry from Haverford College and his M.D. from the University of Massachusetts Medical School. He completed his residency in internal medicine at Tufts Medical Center, a fellowship in nephrology at the Beth Israel Deaconess Medical Center in Boston and an M.S. in clinical care research at the Tufts School of Biomedical Sciences.

Mr. Najim brings a wealth of CMC biopharmaceutical development and cGMP manufacturing experience across multiple biologic expression systems and small molecules. Mr. Najim previously held roles of increasing responsibility at Proteon Therapeutics, including most recently as vice president of manufacturing and process development, and also served as associate director of manufacturing at Dyax Corporation. He received his B.S. in biochemistry from Merrimack College and his MBA from Bentley University.

About Dyne TherapeuticsDyne Therapeutics is pioneering life-transforming therapies for patients with serious muscle diseases. The companys FORCE platform delivers oligonucleotides and other molecules to skeletal, cardiac and smooth muscle with unprecedented precision to restore muscle health. Dyne is advancing treatments for myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). Dyne was founded by Atlas Venture and is headquartered in Waltham, Mass. For more information, please visit http://www.dyne-tx.com, and follow us on Twitter and LinkedIn.

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Dyne Therapeutics Expands Leadership Team with Key Hires - Business Wire

Personalized medicine has taken a big step forward with the launch of non-profit n-Lorem Foundation, which will create patient-tailored antisense oligonucleotide (ASO) therapeutics for people with rare diseases at no cost to the patients. This comes at the same time as custom gene therapies for rare disease patients are being developed, including some combined with CRISPR. As a result, more peopleeven those with ultra-rare diseasescould finally have access to treatments.

The process of developing these treatments is still burdensome and expensive. Only a few patients will benefit at first. But this concept has only been a dream until now, with most of these patients being completely shut out of the typical drug development process. Whats more, the scientists and sponsors pioneering these approaches are hoping to create blueprints for the treatment of ultra-rare diseases in general.

One of the goals is to create a replicable protocol, said Simon Frost, the father of Annabel Frost, a child who suffers from the ultra-rare disease alternating hemiplegia of childhood (AHC). We want to do it for our disease, and then take that process and give it to more patients across many more diseases. Frost, who is CEO of Tiber Capital Group, has been in discussions with multiple labs and investigating several approaches, including ASOs, gene editing, and gene therapy.

The blueprint for the ASO-based approach was a made-to-order treatment for a child with Battens disease, a rare neurodegenerative disorder. In 2018, Timothy Yu, a doctor at Boston Childrens Hospital, sequenced the genome in then six-year-old Mila to diagnose the condition. It turned out Mila had a retrotransposon which had inserted into her CLN7 gene. That aberration was blocking normal protein production by that gene.

Yus team then created a tailor-made ASO, which they called milasen, to mask the mutation in Milas genome, as detailed last year in the New England Journal of Medicine. It took about one year from sequencing to delivery of the therapy. Then, nine months after her treatment began, Milas doctors reported being hopeful about her prognosis, although they noted that she may already have experienced substantial effects from the disease. Hundreds of people, including parents and researchers, have since reached out to Yu to try and have this process replicated. Yus lab is reportedly developing several more personalized oligos, including ones for a rare form of epilepsy and ataxia-telangiectasia, which is a neurological disease.

Addressing the challenges

The demand for more custom ASOs is intense. But there are many issues standing in the way of such therapies.

ASOs are at the point where the investment in the technology has paid off commercially, said Art Krieg, an expert in oligonucleotide therapeutics as well as founder and chief scientific officer of Checkmate Pharmaceuticals. And now Tim Yu has shown the process for making customized ASOs. The questions is whether you can standardize that and could companies find it profitable to develop those therapies. Further, ASOs only block mutations and need to be given for life.

n-Lorem is funded with $1.5 million from Ionis (formerly Isis) Pharmaceuticals, another $1.5 million from Ioniss founder and former CEO Stanley Crooke and his wife Rosanne Crooke (a researcher at Ionis), $1 million from Biogen, and additional funds from other donors. Crooke started Ionis in 1989, as a pioneer in RNA-targeted therapeutics. Today, the company has three drugs on the market and more than 30 in development for a wide range of conditions. Biogen is partnered with Ionis on several of these.

Biogen declined to comment for this article, but sent this statement: Antisense oligonucleotides have been a game changer in the treatment of spinal muscular atrophy (SMA) and we believe they could hold promise in tackling other diseases. So, we are pleased to help support the establishment of n-Lorem Foundation and their mission to provide advanced, experimental RNA-targeted medicines free of charge to patients with ultra-rare diseases.

I knew we could do this and I knew there was a need, said Crooke, who started working on n-Lorem two years ago. But he also realized it was going to be challenging. The patients need a full genomic workup, and you need an investigator who can submit the IND and oversee it, he said. One major development that convinced Crooke the concept was feasible was the 2014 establishment of the Undiagnosed Diseases Network (UDN), a research study funded by the National Institutes of Health Common Fund. The UDN comprises clinical and research experts from across the U.S. who work to solve medical mysteries. As of 2019, 12 UDN clinical sites were open.

While UDN will be a key source of qualified patients, Crooke says n-Lorem will not be restricted to those. We announced the launch last week, and we already have six proposals for patients to treat. But patients need a confirmed genetic diagnosis and treating physicians. Then they must submit a proposal to treat to n-Lorems Access to Treatment Committee.

Another critical issue is the FDAs response. Crooke said he has already approached regulators and they are supportive. But n-of-1 trials like these raise special issues. In an editorial that accompanied the Yu teams report in NEJM, FDA regulators point out the many challenges to evaluating n-of-1 drugs what are the differences between treating one, ten, or thousands of patients? they asked.

But they also acknowledge that the field is moving ahead rapidly. Academic clinicianinvestigators now have the capacity to rapidly uncover specific mutations and pinpoint the putative mechanisms leading to certain rare disease phenotypes. Various ASOs or other compounds can be produced by third parties, and investigators can evaluate them using in vitro assays or animal models, the regulators wrote. FDA is holding a workshop in March on individualized therapies to try and advance thinking around this topic.

Ioniss long experience with ASOs should help in this regard. There are several generations, or classes, of ASOs that the company has developed over the last 30 years. Many years ago I began putting together integrative safety databases about the different classes of ASOs we have developed, Crooke says. Each class has generally similar properties, but they also have important differences such has ligands that work in different organs. Ionis has published on these databases and the properties they reveal, as well as providing the FDA access to the databases. That doesnt mean, however, that researchers will be able to predict all the effects of any ASO in any patient.

Finally, there is the question of cost, which is a particular boondoggle for rare diseases. We know this is feasible but we want to reduce the costs as far as we can, Crooke says. n-Lorem and Biogen are both already working on processes to further cut costs, But we will need to raise even more money to help more patients, he added. Patients shouldnt have to be on the internet raising funds for this.

While hes aware of the challenges, Crooke said hes feeling optimistic. Ive been overwhelmingly impressed with the commitment and advice weve gotten from physicians, experts on antisense and clinical trials,and others. He also hopes more modalities, besides ASOs will be able to work with n-Lorem and start similar endeavors. Im hopeful a gene therapy company can join us or do the same thing, he noted.

Gene therapy too

While there is nothing equal to n-Lorem yet, other researchers are already pursuing customized gene therapies, even for patients who have mutations that are very rare or that are not correctable with standardized gene therapy.

Monkol Lek, for example, is a geneticist at Yale who has been working on a gene therapy for a single patient with an ultra-rare mutation in a muscular dystrophy gene. There are more than 30 types of muscular dystrophy, and some are caused by mutations that affect different genes or varying sections within those genes. Lek himself has limb-girdle muscular dystrophy (MD). When he was first diagnosed, he remembers hearing over and over again that there were no treatments for his condition.

That was enough to inspire Lek to leave a career in IT while in his 20s and obtain degrees in physiology, bioinformatics, and genetics. Soon after he arrived at Yale in 2018, Lek met Rich Horgan, founder of the non-profit Cure Rare Disease, and whose younger brother Terry has a type of MD. Lek analyzed Terrys genomic data, and found he is missing the dystrophin genes promoter region, which needs to be activated in order for that protein to be made. Terry is also missing part of exon 1, which is also necessary to generate the production of dystrophin.

While they originally considered using ASOs, Rich Horgan and Lek realized that wasnt feasible because rather than needing to turn off a gene, they needed to turn on a gene, or at least its promoter.

One twist in this particular case is that people have two alternative versions, or isoforms, of this promoter and exon 1one set in muscle cells and another in brain cells. With that in mind, Lek is using a modified version of CRISPR called no-cut CRISPR to introduce a transcription activator attached to the Cas9 enzyme to turn on the brain-specific set, and thus make up for the deficit in muscle. He uses an AAV and CRISPR activation construct as well as guide RNA to direct the CRISPR to the right spot in the DNA.

Lek has already tested his putative therapy on Terrys cells and successfully corrected the mutated gene in the lab. Next, the treatment will be tested in mice. However, Lek is also exploring the possibility of an n-of-1 clinical trial in which the therapy would only be tested in Terry or anyone with his specific mutation.

Rich Horgans Cure Rare Disease group is now leading new projects for two boys with different forms of Duchenne MD as well as a patient with the limb girdle form of the disease.

Frost, meanwhile, is still investigating the best options for treating his daughter Annabel. His family has spent $250,000 so far and he expects it will cost another $250,000 to $500,000 to reach proof of concept. Annabels mutation is in ATP1A3, a gene that is associated with at least 12 different rare diseases (See table). However, Annabels specific mutation is very rare. Were not sure yet how many of these other conditions would be treated by the same transgene, but it could be a large proportion, Frost said.

Krieg noted that we are not yet at the point where any for profit company will want to develop n-of-1 therapies. It doesnt cost that much to manufacture DNA, and its a fully automated process, he said. It has taken billions of dollars already to get the technology this far and develop applications for some more common diseases. But the overall cost of lifetime treatment is still prohibitive. Right now, I dont know why any company would want to do this, he added. But there will come a time when there are the right incentives and someone will try it.

For families such as Annabel Frosts, these developments are still encouraging, and give them hope that they can help shape the future of the new field of n-of-1 therapeutics. This also supports the idea that more children should undergo whole genome sequencing as soon after birth as possible. With many rare diseases, the damage is compounded the longer the child is untreated. Further, greater understanding of how the full range of possible mutations in any gene impact health, and how that can be treated, will press the field forward.

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Dawn of the Customized Cure - Clinical OMICs News