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Immunology

Is It Too Late to Buy High-Flying Galapagos? – Motley Fool

Galapagos(NASDAQ:GLPG) galloped to all-time highs heading into this week. Although a pullback in the overall market has caused the biotech to give up some of its gains, Galapagos is still up close to 20% year to date and up around 150% over the past 12 months.

Some investors could view Galapagos as valued at a steep premium after its big run-up. But is it really too late to buy the high-flying biotech stock?

Image source: Getty Images.

The primary catalyst behind Galapagos' meteoric rise over the last year was its major collaboration deal signed with Gilead Sciences (NASDAQ:GILD) in July last year. Gilead forked over $5.1 billion for the 10-year agreement, with a $3.95 billion upfront payment and a $1.1 billion equity investment in Galapagos.

Gilead and Galapagos were already partnering on immunology drug filgotinib. The new deal gave Gilead the rights to Galapagos' other late-stage pipeline candidate, idiopathic pulmonary fibrosis (IPF) drug GLPG1690. In addition, Gilead can exercise an option to license any of Galapagos' other candidates.

You can attribute Gilead's interest in Galapagos to the tremendous promise for filgotinib. The experimental drug sailed through late-stage clinical studies targeting rheumatoid arthritis with flying colors. Gilead and Galapagos filed for U.S. and European regulatory approvals for filgotinib in treating rheumatoid arthritis in 2019. Approvals are anticipated later this year in the indication.

And that could be just the start. Gilead and Galapagos are also evaluating filgotinib in other late-stage clinical studies in treating Crohn's disease, psoriatic arthritis, and ulcerative colitis. It's also in phase 2 clinical studies targetingankylosing spondylitis and other inflammatory diseases.

Just how successful filgotinib could be if it wins approval remains to be seen. But peak annual sales of close to $3 billion in treating rheumatoid arthritis and another $3 billion in treating other immunology indications could be possible. Filgotinib's safety profile and convenience (it's an oral medication instead of an injection) could boost its commercial success.

That kind of market potential might make Galapagos' current market cap of under $16 billion seem like a steal. However, it's important to remember that the biotech won't rake in all of the money that filgotinib could make.

Galapagos will market filgotinib on its own inBelgium,the NetherlandsandLuxembourg. It willsplit profits generated by filgotinib equally with Gilead in France,Germany,Italy,Spain, and theUnited Kingdom. In other countries, Galapagos stands to receive tiered royalties between 20% and 30%.

Based on AbbVie'sexperience with blockbuster drug Humira prior to it losing exclusivity in Europe, I expect somewhere around two-thirds of filgotinib's sales will be made in the U.S. If we use a peak annual sales estimate of $6 billion, that would give Galapagos a maximum of $1.2 billion from U.S. sales of the drug. Outside of the U.S., my back-of-the-napkin estimate is that Galapagos would make a little under $1 billion annually.

It's more difficult to predict the financial impact for Galapagos' other drugs. Galapagos thinks that the global market for IPF could be $5 billion by 2025. If we assumedGLPG1690 could capture half of that market, Galapagos would probably make around $750 million annually at peak sales due to its licensing deal with Gilead.

My numbers are admittedly very rough. However, I think that peak revenue from filgotinib andGLPG1690 could bring in somewhere in the ballpark of $3 billion for Galapagos in the future. The company's other earlier-stage programs could boost its sales. In addition, Galapagos is eligible to receive some hefty milestone payments from Gilead if all goes well.

Still, though, we're looking at a stock that currently trades at more than five times sales that it might achieve sometime in the future. I like the potential for Galapagos' products. However, I think that there are other biotech stocks with more room to run. My view is that it is a little too late to jump on the Galapagos bandwagon.

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Is It Too Late to Buy High-Flying Galapagos? - Motley Fool

Immunology

Severe, Difficult-to-Treat Asthma Benefits From Systematic Assessment – Pulmonology Advisor

The majority of patients with severe and difficult-to-treat asthma who underwent systematic assessment improved significantly in at least one key asthma outcome, but with few reliable predicators of response, according to the results of an uncontrolled, observational study published in the Journal of Allergy and Clinical Immunology: In Practice.

In fact, about one-thirdof patients who require maintenance oral corticosteroids may be able todiscontinue steroid use completely after systematic evaluation.

Investigators sought to examine which patients with asthma would respond to systematic assessment and whether the oral corticosteroid burden can be reduced independent of the use of monoclonal biologic agents. They undertook a responder analysis for improvements in the following 4 domains: symptom control, quality of life, disease exacerbations, and airflow obstruction, all of which were evaluated 6 months after the initial assessment. To identify predictors of response, multivariate analyses were conducted for each of these domains. Changes in oral corticosteroid burden were measured as well, stratified by monoclonal biologic use initiated during the assessment.

Of 161 patients who wereassessed systematically, 64% exhibited a reduction in disease exacerbations,54% attained minimum clinically important differences regarding both symptomcontrol and quality of life, and 40% increased their forced expiratory volumein 1 second by 100 mL. Overall, 87% of the participants with asthmademonstrated improvement in at least one of the domains.

The most consistentpredictor of response across all of the domains was poorer baseline asthmastatus. A significant decrease in mean chronic oral corticosteroid dose wasobserved (from 11 mg to 5 mg; n=46; P <.001),even after the exclusion of 7 individuals who initiated monoclonal biologictherapy (from 11 mg to 5.6 mg; n=39; P <.001).

The study results may havebeen limited by the lack of follow-up duration, as the researchers did not assessresponse beyond 6 months.

The investigators concluded that the use of systematic assessment in patients with severe or difficult-to-treat asthma is beneficial for most of these individuals. However, [n]o single outcome was sufficient to assess patient response to interventions, and a combination of measures remains necessary in this area, the researchers added.

Disclosure: Several study authors declared affiliations with thepharmaceutical industry. Please see the original reference for a full list ofauthors disclosures.

Reference

Denton E, Lee J, Tay TR, et al. Systematic assessment for difficult and severe asthma improves outcomes and halves oral corticosteroid burden independent of monoclonal biologic use [published online January 15, 2020]. J Allergy Clin Immunol Pract. doi:10.1016/j.jaip.2019.12.037

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Severe, Difficult-to-Treat Asthma Benefits From Systematic Assessment - Pulmonology Advisor

Immunology

What’s Behind Mallinckrodt’s Better-Than-Expected Q4 Results – Motley Fool

Investors could be experiencing whiplash from the big up-and-down swings forMallinckrodt(NYSE:MNK). There have been at least half a dozen moves of at least 20% for the stock in just the first two months of 2020.

Mallinckrodt announced its 2019 fourth-quarter and full-year results before the market opened on Tuesday. And the stock had yet another big jump. Here are the highlights from the company's Q4 update.

Image source: Getty Images.

Mallinckrodt announced Q4 revenue of $804.9 million, down from the $834.9 million reported in the same quarter of the previous year. This result topped the average analysts' revenue estimate of $772.52 million.

The company reported a net loss in the fourth quarter of $1.2 billion, or $13.76 per share, based ongenerally accepted accounting principles (GAAP). This reflected considerable improvement from the GAAP net loss of $3.7 billion, or $44.64 per share, in the prior-year period.

Mallinckrodt's non-GAAP adjusted bottom line looked much better, though. The company posted adjusted net income of $2.40 per share, up 10% year over year. It also easily beat the Wall Street consensus earnings estimate of $2.05 per share.

The drugmaker's biggest segment didn't perform very well in Q4. Net sales for Mallinckrodt's specialty brands segment slipped 6.3% year over year to $611.4 million. Sales for Acthar Gel sank 17.8% to $232.6 million due to continued reimbursement headwinds. Net sales for Amitiza fell 21.2% to $50.9 million in the wake of increased competition.

There were some bright spots, though. Net sales for Inomax climbed 3.7% year over year to $143.8 million. Ofirmev's net sales jumped 28.2% to $111.8 million. Net sales for the Therakos immunology platform increased by 11.1% year over year to $63.3 million.

Mallinckrodt's specialty generics segment also performed relatively well. Fourth-quarter net sales for the segment rose 6% year over year to $193.5 million.

The company's GAAP bottom line improved significantly from the prior-year period, primarily due to a bigger non-restructuring impairment charge in the fourth quarter of 2018. This was partially offset, however, by a $1.64 million opioid litigation settlement charge in Q4 of 2019.

Mallinckrodt's biggest news of the day wasn't its Q4 results. The company also announced an agreement in principle to settle all remaining opioid claims against it and its subsidiaries. This agreement involves Mallinckrodt's specialty generics businesses filing for Chapter 11 bankruptcy. Mallinckrodt would pay $1.6 billion over eight years and fork over warrants that would allow a trust set up as part of the agreement to buy 19.99% of the company's outstanding shares.

Investors liked the deal, with the pharma stock rising as much as 51.7% on Tuesday at one point. The agreement would enable Mallinckrodt to finally remove the dark cloud that's been hovering over its head related to opioid litigation. It would also allow the company's specialty brands business to avoid bankruptcy.

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What's Behind Mallinckrodt's Better-Than-Expected Q4 Results - Motley Fool

Immunology

Latex detection dogs help people with allergy return to normal life – TODAY

Ellen Heilman has been living with a latex allergy since she was 5 a worsening sensitivity that can leave her struggling to breathe if theres a rubber band, balloon or latex glove nearby.

It got to the point where I really couldnt leave my house safely. At 21 years old, that was not cool, Heilman, a graduate student who is now 22 and lives in Odenton, Maryland, told TODAY.

I used to be on high alert all the time, always looking over my shoulder: Where are the balloons? Where are the gloves? Im not safe anywhere. Now, I know that he has my back, that we are a team and that together, well find it and well be safe.

He is Francis, a 3-year-old service dog trained to detect natural rubber latex and alert Heilman to its presence. The black lab goes with her everywhere, from Target to class, sniffing for the allergen as they enter the building or room.

His highly-sensitive nose can recognize latex through cabinet seams and under doors. If Francis detects it, he sits down in a distinct way that Heilman recognizes right away. Depending on the situation, the latex object is either taken away or Heilman leaves the area.

I went from being able to go nowhere to being pretty much able to go anywhere, she said. Its a huge difference it makes things so much better for me.

Dogs have been trained to help people with peanut allergies for years. There are even gluten-sniffing canines.

But their role in latex detection has been rare, though its definitely on the rise, said Ciara Gavin, founder of Allergen Detection Service Dogs, a facility in Colorado Springs, Colorado, that provided Heilmans canine. The business used to focus mostly on training dogs to detect peanuts.

Lately, Ive had a lot of calls about latex detection, Gavin said. People are finding out more about it. Instead of living in a hopeless kind of situation where they feel like, I cant go anywhere because of this allergy, theyre finding out there might be hope.

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She placed her first latex detection dog two years ago. Now, one or two of the four dogs total she places each year are latex detection dogs, usually black labs.

Fewer than 1% of people in the U.S. have a latex allergy, according to the Asthma and Allergy Foundation of America. But that proportion rises to 8-12% among health care workers who are exposed to latex gloves or medical products containing the substance, the Occupational Safety and Health Administration noted.

People can react when they breathe in latex fibers in the air or touch latex in objects such as condoms, handbags, athletic shoes, tires, waistbands, rubber toys, baby bottles and pacifiers.

Symptoms can include hives, itching, wheezing, a runny nose, chest tightness and difficulty breathing. They can be part of anaphylaxis, a severe, whole-body life-threatening allergic reaction.

The allergy usually develops after many previous exposures to latex, according to the American College of Allergy, Asthma & Immunology. Studies have called it a growing disease that can occur at any age.

Amy Crawford, 47, first found out she had a latex allergy last year when she was blowing up a balloons for a childrens party.

The next thing I know, I cant breathe, my face is just swollen and red, and covered in bumps and hives. I ended up being taken to the emergency room, Crawford, a middle school teacher in Humble, Texas, recalled.

They told me: You have a latex allergy. Go see a doctor. Get a [medical alert] bracelet.

Her only clue before that incident was a sensitivity to avocados, strawberries and kiwis. People with a latex allergy can also be allergic to foods that share certain proteins with latex, according to the American Academy of Allergy, Asthma & Immunology.

Crawford has now been to the emergency room six times in less than a year. Exposure to latex, whether airborne or via skin contact, can cause her throat to close up to the point where she cant swallow and has trouble breathing.

She carries an EpiPen with her everywhere she goes and wears a mask as a precaution. Crawford doesnt travel anywhere and cant take her two sons, ages 8 and 14, to birthday parties anymore.

Shes crowdfunding for a latex detection dog, which will cost about $17,000.

Im looking forward to just being able to just walk into a room, because I cant do that now. I have to peak in and look: Are there balloons? Is there anything that could affect me? Crawford said. My kids are really suffering because theyre terrified all the time.

It takes six months for a dog to be trained, Gavin said. The new owners and their canines then spend two weeks getting to know each other under the supervision of a trainer to make sure they understand each others signals.

The dogs are taught to sit and stare at the source of the latex. Theyre at least 95% accurate, but that estimate can depend on air currents, the size of the item and where its located, Gavin noted.

Heilman and her service dog Francis bonded the minute they met, she recalled.

At this point, it is kind of like we are one being. He uses his nose, I use my eyes and together we make sure I am safe, she said.

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Latex detection dogs help people with allergy return to normal life - TODAY

Immunology

Bicycle and Genentech Forge Immuno-Oncology Collaboration Worth up to $1.7 Billion – BioSpace

Shares of U.K.-based Bicycle Therapeutics are climbing this morning after the company announced it entered into a strategic immuno-oncology collaboration with Genentech to discover, develop and commercialize novelBicycle-based immuno-oncology therapies.

The collaboration has a value of up to $1.7 billion if all milestones are hit. Under terms of the agreement, Bicycle will receive an upfront payment of $30 million to focus its proprietary bicyclic peptides platform on a wide range of immuno-oncology targets. The U.K. companys proprietary discovery platform allows for rapid screening of novel targets to identifyBicyclesand the ability to readily conjugate these together to create novel molecules that may overcome the potential limitations of other modalities. Bicycles are fully synthetic short peptides constrained with small molecule scaffolds to form two loops that stabilize their structural geometry. This constraint facilitates target binding with high affinity and selectivity, which makes Bicycles attractive candidates for drug development, the company said.

Genentech, a Roche company, brings to the collaboration its knowledge of immuno-oncology drug discovery and emerging target biology, as well as its development and commercialization expertise, Bicycle said this morning.

Bicycle Chief Executive Officer Kevin Lee said the collaboration with Genentech recognizes the potential of his companys differentiated technology, which allows it to specifically direct immune cell stimulators and other payloads to tumors in a highly targeted manner. Additionally, Lee said, the flexibility of the companys platform will enable the rapid exploration of structure-activity relationships to fully optimize candidate molecules.

In its announcement, Bicycle did not identify the cancer targets it will focus on in its collaboration with Genentech. The company only said it will collaborate with Genentech on the discovery and pre-clinical development of novel Bicycle-based immunotherapies against multiple targets.

James Sabry, Roches head of Pharma Partnering, said Bicycles represent a novel therapeutic modality that have shown promise as modulators of several types of tumor-killing immune cells.

By leveraging Genentechs deep understanding of cancer immunology and Bicycles technological expertise, we hope to create a new wave of immunotherapy options to expand the population of patients who could potentially benefit from this powerful treatment paradigm, Sabry said in a statement.

Bicycle will be responsible for discovery research and early pre-clinical development up to candidate selection and Genentech will be responsible for further development and commercialization upon the selection of candidates. None of Bicycles wholly-owned oncology pipeline, including its immuno-oncology candidates, are included in the collaboration, the company noted. Bicycles lead product candidate, BT1718, is a Bicycle Toxin Conjugate (BTC) that targets MT1-MMP. BT1718 is being investigated in an ongoing Phase I/IIa clinical. The company is also investigating BT5528, a BTC targeting tumor antigen EphA2, in patients with advanced solid tumors associated with EphA2 expression.

The collaboration with Genentech follows a partnership with Cancer Research UK to develop BT7401, a multivalent Bicycle CD137 agonist, through a Phase IIa clinical study.

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Bicycle and Genentech Forge Immuno-Oncology Collaboration Worth up to $1.7 Billion - BioSpace

Immunology

Meet the Company That Just Might Prevent a Global Recession – Motley Fool

You might think it's crazy to even remotely suggest that one company could singlehandedly thwart the onset of a global economic recession. But make no mistake -- that's exactly what I'm doing.

I think the odds are pretty high right now that a recession could be on the way. The coronavirus outbreak that started in China has now spread to many countries around the world. It's already making a significant financial impact. There's a real chance that the epidemic could become a true pandemic and trigger a global recession.

Multiple companies are racing to develop drugs or vaccines that could contain the spread of the current coronavirus strain and COVID-19, the disease caused by the virus. None, though, is in as strong of a position to succeed as Gilead Sciences (NASDAQ:GILD) is. And as crazy as it might sound, Gilead just might prevent a global recession.

Image source: Getty Images.

The first assumption with my premise is that the coronavirus could actually spark a global recession. Don't take my word for it, though. Consider an analysis performed by the Congressional Budget Office (CBO) in 2005 and 2006.

Fifteen years ago, it wasn't the current strain of coronavirus that was worrying governments and investors. Instead, it was the avian flu. Bill Frist, the Senate majority leader at the time, requested that the CBO conduct a study to evaluate the possible macroeconomic impact of an avian flu pandemic.

The CBO determined that a severe avian flu pandemic could cause U.S. gross domestic product (GDP) to fall by around 4.25%. That's more than enough to throw the U.S. into an economic recession. As the U.S. goes, so goes the rest of the world.

Keep in mind that at the beginning of 2006, there had been 142 cases worldwide of avian flu with 74 deaths. So far, there have been over 80,000 cases of the coronavirus across the world with more than 2,700 deaths. It stands to reason that the CBO's analysis related to the avian flu is applicable for the coronavirus -- and the negative economic impact could be even worse.

Major companies are already feeling the effects of the viral outbreak. Applestated last week that it will miss its revenue guidance for the first quarter of 2020 because of the coronavirus. Mastercardreduced its Q1 revenue guidance as a result of the impact that the coronavirus is having on travel. Dun & Bradstreet estimates that at least 51,000 companies across the world will be negatively affected by the virus, including 163 members of the Fortune 1000.

All of this negativity could be a moot point if a safe and effective treatment or vaccine for the virus becomes available. That's where Gilead Sciences enters the picture.

Gilead originally developed experimental antiviral drug remdesivir to treat the Ebola virus. While the drug wasn't as effective as hoped with treating Ebola, it showed promise in preclinical testing in treating two other viruses -- MERS and SARS. Both MERS and SARS are members of the coronavirus family and are similar in structure to the2019-nCoV strain of coronavirus that's causing concerns now.

Over the past four weeks, Gilead has initiated two clinical studies in China evaluating patients with COVID-19. It began a U.S. clinical study earlier this week. The biotech is also working with government and non-government organizations to supply remdesivir to COVID-19 patients as an emergency treatment.

Other drugmakers are also scrambling to test experimental drugs and vaccines. They range from big pharma companies including AbbVie, GlaxoSmithKline, and Johnson & Johnsonto small biotechs such as Inovio, Moderna, and Novavax.

But there's one clear leader at this point -- Gilead. World Health Organization (WHO) assistant director-general BruceAylward stated in a press conference earlier this week that "there is only one drug right now that we think may have real efficacy and that's remdesivir."

Gilead expects to report results from its clinical studies ofremdesivir in April. If those results are positive, expect countries across the world to want the antiviral drug even before any regulatory approvals are granted. Gilead has already ramped up its production efforts and is keeping governments updated on its progress.

It's quite possible that the global economy could hinge on how the clinical studies forremdesivir turn out. Overwhelmingly positive results could enable governments and investors to breathe a huge collective sigh of relief if the drug demonstrates the potential to effectively treat COVID-19 and contain the economic impact of the coronavirus.

Gilead Sciences could end up being a hero to the rescue. But while the biotech stock has jumped on the news of its progress withremdesivir, Gilead might not enjoy as big of a hero's reward as you might think.

Bank of America analyst Geoff Meacham projects that Gilead would likely generate at most $2.5 billion in revenue from its antiviral drug. That's a lot of money, but it represents only around 11% of Gilead's current total revenue and would only give the company a temporary boost.

Gilead just might prevent a global recession. For investors, though, the biotech's HIV franchise and promising immunology drug filgotinib that could win FDA approval later this year are better reasons to consider buying the stock than its coronavirus drug is.

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Meet the Company That Just Might Prevent a Global Recession - Motley Fool

Immunology

Breakthrough research may lead to improved therapeutic options for people with asthma – News-Medical.net

Researchers from Trinity College Dublin have made a breakthrough that may eventually lead to improved therapeutic options for people living with asthma. The researchers have uncovered a critical role for a protein (Caspase-11), which had previously never been implicated in the disease.

They report their findings today [Wednesday 26th February 2020] in leading journal Nature Communications.

Lead author Zbigniew Zaslona, working with a team led by Luke O'Neill, Professor of Biochemistry in the School of Biochemistry and Immunology in the Trinity Biomedical Sciences Institute, has been exploring the role that inflammation plays in asthma - a very common and often serious disease of childhood.

Ireland has one of the highest incidences of asthma in Europe, which in its most severe form remains difficult to treat and can be fatal. Caspase-11 is a protein with an important role in defending against bacteria, but the team in Trinity has found that when it is over-active it can provoke a damaging inflammatory reaction. When this happens, it is likely to be a key driver of allergic inflammation in the lungs of asthmatics.

Dr. Zaslona said:

Caspase-11 can cause cells to die, which is a very inflammatory event as the cells then release their contents, which can irritate tissues in our body. We have found that Caspase-11 is a key driver of inflammation in the airways in asthma. This causes the signs and symptoms of asthma which most notably involves difficulty breathing."

Although symptoms of mild asthma can be managed with current therapies, severe asthma remains very difficult to treat and asthma rates are constantly on the rise.

Dr. Zaslona added:

A variety of irritants such as airborne pollutants, certain types of pollen and house dust mites can induce cell death in the lungs. Our work suggests that Caspase-11 is sensing these noxious things and causing disease."

Professor O'Neill said:

Caspase-11 - or it's human equivalent, which is Caspase-4 - has never been implicated in asthma before so we think it holds great promise as a possible target for new drugs to treat this common, debilitating disease."

Source:

Journal reference:

Zasona, Z., et al. (2020) Caspase-11 promotes allergic airway inflammation. Nature Communications. doi.org/10.1038/s41467-020-14945-2.

Posted in: Medical Science News | Medical Research News | Medical Condition News

Tags: Asthma, Bacteria, Biochemistry, Breathing, Cell, Cell Death, Drugs, Immunology, Inflammation, Lungs, Mites, Protein, Research

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Genetics

First Prospective Study Shows +RNAinsight Identifies More Patients with Increased Risk for Hereditary Cancer Than DNA-Only Testing – PRNewswire

ALISO VIEJO, Calif., Feb. 25, 2020 /PRNewswire/ -- Ambry Genetics(Ambry), a leading clinical genetic testing lab, announced the publication of a studyin Nature Partner Journal Precision Oncology finding that RNA genetic testing, conducted at the same time as DNA testing, identifies more genetic mutations that increase genetic cancer risk than DNA testing alone. Through +RNAinsight,Ambry is the first and only lab to offer concurrent RNA and DNA genetic testing for hereditary cancer risk as a commercially available clinical test.

Inherited mutations variants or errors in our DNA that increase cancer risk play a major role in about five to 10 percent of all cancers. Genetic testing identifies these inherited mutations and is a critical tool to prevent hereditary cancers or treat them early. Standard DNA testing for hereditary cancer risk excludes portions of DNA, thereby missing some mutations. In addition, DNA testing can produce inconclusive results and fail to determine whether a variant increases cancer risk. These limitations impact patients and their families because doctors may not have the information needed to recommend appropriate preventive, early-detection, or therapeutic steps. Additionally, relatives may not be referred for genetic testing and obtain the care they would otherwise have gotten if they had learned they had mutations.

Adding RNA genetic testing at the same time as DNA testing helps address these limitations. Specifically, RNA genetic testing is an additional line of evidence that helps determine that an uncertain result from DNA-only testing is actually benign (normal) or pathogenic (disease-causing). It also helps identify mutations that DNA-only testing misses. In the study published today, co-authors from Ambry researchers describe their scalable and targeted approach to RNA genetic testing that is performed concurrently with DNA genetic testing (+RNAinsight), showing that +RNAinsight identified more mutations than DNA-only testing.

Ambry, in collaboration with 19 other leading clinical institutions across the country, including Mass General Cancer Center, Huntsman Cancer Institute, and the Perelman School of Medicine at the University of Pennsylvania, looked at 18 tumor suppressor genes where the loss of function is known to be associated with increased cancer. A prospective study on the first 1,000 patients sent in for hereditary cancer testing using RNA testing coupled with DNA was performed.

The study found that RNA testing identified seven patients with pathogenic mutations that would otherwise have received negative or inconclusive results on DNA testing alone. For six of these seven cases, substantial changes to medical management could be or were recommended based on current guidelines.

"The study findings demonstrate both the feasibility and clinical utility of adding concurrent RNA genetic testing to determine hereditary cancer risk," said Tyler Landrith, Ph.D., an Ambry scientist and study co-author. "+RNAinsight provides healthcare providers with more accurate results to inform patient care."

Notably, the prospective analysis showed a 9.1 percent relative increase in diagnostic yield than DNA testing alone. Adding RNA genetic testing also resulted in a 5.1 percent relative decrease in the number of patients that would have received inconclusive results with DNA testing alone and would not have learned whether they had increased cancer risk.

"Paired RNA and DNA genetic testing has given answers to my patients who have struggled for years with inconclusive results that left them feeling helpless," said Community Health Network Genetic Counselor Rebekah Krukenberg. "With +RNAinsight, I know that I'm providing my patients with the most accurate and conclusive information about their risks for hereditary cancer."

The study also validated the accuracy of +RNAinsight, establishing a large control dataset of healthy patients. This dataset allowed study co-authors from Ambry researchers to establish a baseline for benign and disease-causing variants across the genes tested.

Studies have previously demonstrated the benefits of RNA genetic testing, but this testing has been traditionally performed as a follow-up to inconclusive DNA testing. This approach to RNA testing has limitations that +RNAinsight does not. A previous studyfrom Ambry showed that only 10 percent of patients invited to receive RNA testing after having undergone DNA testing actually sent in samples. Moreover, retrospective RNA testing only looks at targeted variants and not a full range of possible mutations. Given these limitations, Ambry has made RNA genetic testing available to all patients at the same time as DNA testing through +RNAinsight.

+RNAinsight is now available through doctors and genetic counselors around the country. For more information on RNA genetic testing, please go to http://www.ambrygen.com/RNAinsight.

ABOUT AMBRY GENETICsAmbry Genetics, as part of Konica Minolta Precision Medicine, excels at translating scientific research into clinically actionable test results based upon a deep understanding of the human genome and the biology behind genetic disease. Our unparalleled track record of discoveries over 20 years, and growing database that continues to expand in collaboration with academic, corporate and pharmaceutical partners, means we are first to market with innovative products and comprehensive analysis that enable clinicians to confidently inform patient health decisions. We care about what happens to real people, their families, and the people they love, and remain dedicated to providing them and their clinicians with deeper knowledge and fresh insights, so together they can make informed, potentially life-altering healthcare decisions. For more information, please visitambrygen.com.

For more information on risk factors for hereditary cancer, please visit cancer.gov's fact sheet on hereditary cancer and genetic testing.

ABOUT +RNAInsight+RNAinsight,paired with Ambry Genetics' hereditary cancer DNA tests, uses next-generation sequencing to concurrently analyze a patient's DNA and RNA, another layer of genetic information. +RNAinsight identifies more patients who have mutations that increase their cancer risks than through standard DNA-only testing by overcoming limitations of DNA testing. +RNAinsight enables more accurate identification of patients with increased genetic risks for cancer, finds actionable results that may otherwise be missed, and decreases the frequency of inconclusive results. +RNAinsight is now available through doctors and genetic counselors around the country. For more information on +RNAinsight, please go towww.ambrygen.com/RNAinsight.

Press Contact:Liz Squirepress@ambrygen.com (202) 617-4662

SOURCE Ambry Genetics

https://www.ambrygen.com

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First Prospective Study Shows +RNAinsight Identifies More Patients with Increased Risk for Hereditary Cancer Than DNA-Only Testing - PRNewswire

Neuroscience

Depletion and repopulation of microglia could be a future therapy for TBI – Drug Target Review

Researchers have shown that by effectively resetting the microglia, recovery of mice after a traumatic brain injury (TBI) was improved.

Depleting microglia and allowing for their repopulation limited brain cell loss as well as cognitive and motor deficits in a murine model of traumatic brain injury (TBI). The researchers suggest their discovery could be used as a novel therapeutic for TBI in humans.

The team, from the University of Maryland School of Medicine (UMSOM), US, targeted overactive microglia in mice with TBIs by administering a CSF-1R inhibitor for one week a month after the initial injury. They chose this point as it is a time at which animals have brain inflammation and neurological deficits.

According to the results of the study, published in Neuroscience, the CSF-1R inhibitor depleted 95 percent of overactive microglia, reducing neurotoxic inflammation. Several weeks later, these cells had regenerated but with characteristics similar to normal microglia, with less inflammatory features.

Use of experimental CSF-1R inhibitor drug reduced inflammation in microglia cells after treatment (right) compared to before treatment (left) (credit: University of Maryland School of Medicine).

The paper states that the CSF-1R inhibitor treated mice recovered better from their TBI than the untreated control group. The population that received the drug had less tissue and neuron loss and significantly better motor and cognitive performance.

We were surprised to see that the extent to which such late treatment could reverse the inflammatory state and the cognitive effects of experimental TBI, said study co-author Dr Rebecca Henry, Research Associate in Anesthesiology at UMSOM. This was a proof-of-concept study that depletion and subsequent repopulation of microglia cells after injury has a strong protective effect, but we clearly need more research to better understand this process before clinical translation.

These pre-clinical studies suggest that the consequences of TBI on brain degeneration and related neurological impairment may be modifiable quite long after injury, said study co-author Dr Alan Faden, the David S. Brown Professor in Trauma at UMSOM. We can potentially alter these effects by even highly delayed targeting of inflammatory pathways, a finding at odds with widely accepted views about treating head injury.

The researchers now intend to explore which genes are driving inflammation and overactivation in microglia following a TBI.

This is an intriguing finding that points to an important role that inflammation plays in chronic debilitation from brain injuries, said UMSOM Dean Dr E Albert Reece, MBA, University Executive Vice President for Medical Affairs and the John Z and Akiko K Bowers Distinguished Professor. Future studies will hopefully lead to new treatments for severe TBI that destroys a patients quality of life.

Read more from the original source:
Depletion and repopulation of microglia could be a future therapy for TBI - Drug Target Review

Neuroscience

New California Bill Aiming to Eliminate Racial And Other Biases in Hiring – Sacramento Observer

(CBM) Imagine applying for a job online.

But instead of a hiring manager or some pre-screening software reviewing your application and pushing it along or eliminating it based on personal biases or other random criteria a company sets up, a smart computer program that is agnostic does the filtering, determiningwhether you are a good fit for the job or not.

Relying only on your qualifications and experience, the program does not consider factors like your name, your zip code, social connections or where you went to school in the screening process.

Sounds too futuristic? Well, the future may be right now at least in California.

On Friday, lawmakers in California introduced SB 1241 or the Talent Equity for Competitive Hiring (TECH) Act. The bill sets a new legal high bar against discrimination in hiring by writing clear guidelines for employers to follow that allow them to modernize their recruiting processes using technological tools that reduce bias, leading to a more diverse workforce.

Sen. Lena Gonzalez (D-Long Beach) introduced the legislation in the Senate. Assemblymember Reggie Jones-Sawyer (D-South Los Angeles), Sen. Steven Bradford (D-Gardena), and Assemblymember Mike A. Gipson (D-Carson) are co-authors.

California has a growing opportunity gap that leaves many families and communities in our state behind, said Gonzalez after she introduced the bill in Long Beach along with leaders from community based organizations and social justice groups. Hiring discrimination plays a significant role in our current inequality. The TECH Act will help ensure access to jobs that offer competitive wages and upward mobility for all our residents.

The TECH Act states assessment technologies will be considered in compliance with anti-discrimination rules if: 1) they are pre-tested for bias before being deployed and found not likely to have an adverse impact on the basis of gender, race or ethnicity; 2) outcomes are reviewed annually and show no adverse impact or an improvement of hiring among underrepresented groups; and 3) their use is discontinued if a post-deployment review indicates adverse impact.

Last September, the California Assembly voted unanimously to pass ACR 125, also known as the Fair Hiring Resolution. ACR 125 was a call to action for the states lawmakers to pass legislation that tackles implicit racial and social biases in corporate hiring by creating clear rules of the road for how employers can use these smart technologies.

Five months later, their motion has become a reality.

Innovative technologies for hiring and promotion, including artificial intelligence and algorithm-based technologies, have the potential to reduce bias and discrimination in hiring and promotion based on protected characteristics, such as socioeconomic status or status as a formerly incarcerated person, the resolution read.

At the same time, these technologies can help employers reach larger and more diverse pools of qualified talent and better identify candidates with the right skills and abilities to succeed, it went on to make the case for the merits of the legislation.

Jones-Sawyer and Gonzalez introduced the resolution in August last year. It was co-authored by Assemblymember Sydney Kamlager-Dove (D-Los Angeles), Assemblymember Chris Holden (D-Pasadena), and Assemblymember Evan Low (D-Silicon Valley).

California is one of the most diverse states in the nation. Our diversity is our strength, but corporate executive offices and boardrooms across our state frequently fail to reflect the same diversity, Jones-Sawyer points out.

Just look at San Franciscos Silicon Valley high tech sector as an example, he explained. Women make up just 36.7 percent of the workforce; 3.3 percent of the workforce is Black; and only 6.6 percent is Hispanic. Thats unacceptable.

The TECH Act builds on a series of laws California has passed in recent years to fight discrimination in hiring, such as ban the box legislation prohibiting employers from asking about an applicants criminal history before giving a conditional job offer, according to Jones-Sawyer.

Frida Polli is a co-founder at Pymetrics, a company that makes neuroscience games using artificial intelligence that are designed to eliminate the biases in hiring the resolution intends to prevent.

Before we release the technology, we look at the outcomes and audit it. And we go through the audit, she told California Black Media. We are giving an objective data point or an objective score for employers. It is mitigating the human biases of employers. All of us are biased. The way a lot of these tools work are customized for each role. We have employees working with each of our clients. It is not a one-size-fits-all solution.

According to Pymetrics, the companys AI tools is based on decades of research and technology developed by the global neuroscience community.

They are widely considered the gold-standard of neuroscience research, and measure established building blocks of cognitive and emotional functioning, akin to the DNA of cognition and personality, the company website reads.

Jones-Sawyer says he realizes that there will be kinks to work out in what the law legislates but he hope this technology can be used everywhere, starting with large companies in the state.

At the beginning we will have to prove the technology, Jones-Sawyer concedes. We will have to offer it and hope their some companies are willing to take a chance. If we mandate it, it could sabotage us before we get out of the gate. We will have to be sure there is not government overreach with this.

California has some of the strongest legal employee protections in the country. But even with the existing state and federal laws that prohibit discrimination in hiring and firing, Black and Latino workers still face significant discrimination in hiring, according to a 2017 Harvard Business Review report.

The study found that employers called back White applicants 36 percent more times than they did Black applicants with identical resumes. For Latinx applicants, that differential was 24 percent. It also found that the standardized tests some employers use to screen potential employees have been proven to identify qualified candidates, but leads to biased outcomes.

In another study conducted in 2012, researchers switched the names on women resumes to male names. The swap improved ratings from professors who were reviewing the resumes to select candidates for STEM research positions.

This is an amazing, amazing initiative, says Rhonda Gregory, co-founder of the National Diversity Coalition, a non-profit social justice organization that supports the legislation. I think it needs to be sooner than later. Im all for it. For me, this is so compelling. You look at a persons name or gender or area where they are from and people tend to say oh no I dont want to deal with that.

By Tanu Henry | California Black Media

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New California Bill Aiming to Eliminate Racial And Other Biases in Hiring - Sacramento Observer