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Archive for November, 2018

Gene-editing Second International Summit in Hong Kong: George Church, “Let’s be quantitative before we start being accusatory”

Reporter: Aviva Lev-Ari, PhD, RN

2.1.4.3

2.1.4.3   Gene-editing Second International Summit in Hong Kong: George Church, “Let’s be quantitative before we start being accusatory”, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

UPDATED on 11/30/2018

Gene editing takes a foreboding leap forward

He Jiankui. Photo: Zhang Wei/Chinese News Service/VCG via Getty Images

 

China is temporarily suspending the work of scientists who claimed twins were born after being genetically edited as embryos.

Why it matters: The scientific consensus is that gene editing embryos at this stage of science is “irresponsible.” But, while this particular experiment has not been verified, the fact is the technology is available to researchers, so there’s a growing call for international limitations on its use.

ICYMI: Chinese scientist He Jiankui announced earlier this week that twins were born after he used the gene-editing tool CRISPR-Cas9 to cut the CCR5 gene that’s known to play a role in HIV infection.

  • He stirred even more dismay when he mentioned the possibility of a second pregnancy.
  • China currently bans human implantation of gene-edited embryos. Its Ministry of Science and Technology is investigating the claims, per Xinhua.

There are concerns about the safety, efficacy and possible mosaicism, where a person can contain genes in both its edited and unedited forms, from cutting genes.

  • Editing embryos raises an even bigger concern: The genetic changes and all the unknowns around them can be passed down to future generations.

Between the lines: Not everyone viewed it as a complete disaster. For instance, Harvard Medical School’s George Daley suggested that it may be time to reconsider the massive amounts of research done over the past several years and look for plausible methods of moving forward.

What to watch: Scientists are cautious about predicting what the impact will be, in part because the details of this claim are thin. However, the debate is heating up and one concern is it will dampen important research.

  • Medical ethicist Jonathan Moreno from the University of Pennsylvania says the situation reminds him of other times in history where there were tremors in the science world, like the death of 18-year-old Jesse Gelsinger in 1999 from a gene therapy trial that led to years of diminished research.

The bottom line: The alarm over what could be next is real. But scientists hope the current debate will promote consensus on firm limits and promote transparency.

Go deeper:

SOURCE

From: Andrew Freedman <andrew.freedman@axios.com>

Date: Thursday, November 29, 2018 at 5:33 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Axios Science: About that climate report — Gene editing takes a foreboding step — Building in harms’ way

He Jiankui spoke at the second international summit on human genome editing in Hong Kong. (Alex Hofford/EPA-EFE/Shutterstock)

CRISPR-baby scientist faces the music

The scientist who claims to have helped produce the first people born with edited genomes faced a tough crowd yesterday at a gene-editing summit in Hong Kong. He Jiankui gave a 20-minute talk about his unpublished work in animals and humans before opening a 40-minute Q&A session (watch it here). He faced difficult questions about the ethics of his work and his choice to keep it mostly under wraps until after the babies were born, and left many unanswered.

Meanwhile, prominent geneticist George Church is one of the few scientists who seem to be looking on the bright side of He’s controversial claim. “Let’s be quantitative before we start being accusatory,” Church told Science. “As long as these are normal, healthy kids it’s going to be fine for the field and the family.”

Nature | 9 min read & Science | 6 min read

Read more: Genome-edited baby claim provokes international outcry

SOURCE

From: Nature Briefing <briefing@nature.com>

Reply-To: Nature Briefing <briefing@nature.com>

Date: Thursday, November 29, 2018 at 12:18 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: CRISPR-baby scientist faces the music at gene-editing summit

See

SAVE

The ethical red flags of genetically edited babies

Driving the news: Chinese scientist He Jiankui announced Sunday night that a pair of twin girls had been born from embryos he modified using the gene-editing tool known as CRISPR.

  • He hasn’t provided solid proof, but if it‘s true, it would be the first time the technology has been used to engineer a human.

What they’re saying: The inventors of CRISPR technology did not seem pleased with the development — one called for a moratorium on implantation edited embryos into potential mothers.

  • “I hope we will be more cautious in the next thing we try to do, and think more carefully about when you should use technology versus when you could use technology,” said Jessica Berg, a bioethicist at Case Western Reserve University.

Between the lines: Several specific factors in He’s work sent up ethical red flags.

  • Many scientists had assumed that, when this technology was first used in humans, it would edit out mutations tied to a single gene that were certain to cause a child pain and suffering once it was born — essentially, as a last resort.
  • But He used CRISPR to, as he put it, “close a door” that HIV could have one day traveled through. That has prompted some speculation that this project was more about testing the technology than serving an acute medical need.
  • “That should make us very uneasy about the whole situation,” Berg said. “Of all the things to have started with, it does make you a little suspicious about this particular choice.”

The intrigue: There’s a lot we still don’t know about He’s work, and that’s also contributing to an attitude of skepticism.

  • How many embryos did he edit and implant before these live births?
  • How will he know it worked? As the children age, they’ll likely have their blood drawn and those samples will be exposed to HIV in a lab, but researchers aren’t going to tell them to go out and have unprotected sex or use intravenous drugs — another reason HIV seems like an odd starting place for human gene editing.
  • How did this even happen? The university where He worked said he was on leave, and Chinese officials have said he’s under investigation. But gene editing is a pretty hard thing to freelance.

The other side: He defended his work in a video message, saying, “I understand my work will be controversial but I believe families need this technology and I’m willing to take the criticism for them.”

  • “Their parents don’t want a designer baby, just a child who won’t suffer from a disease which medicine can now prevent,” He said.

Yes, but: Now that this threshold may have been crossed, attempts to create “designer babies” — within the limitations of what CRISPR can do — probably aren’t far off, some experts fear.

  • There are “likely to be places that are less regulated than others, where people are going to attempt to see what they can do,” Berg said. “I wouldn’t say everything in the world has changed now, but it’s certainly the next step.”
SOURCE

https://www.axios.com/genetic-editing-baby-china-ethics-controversy-b33f8414-8b83-445c-bad5-d8407f8841f4.html

https://pharmaceuticalintelligence.com/2018/11/26/jennifer-doudna-and-npr-science-correspondent-joe-palca-several-interviews/

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The Future of Precision Cancer Medicine, Inaugural Symposium, MIT Center for Precision Cancer Medicine, December 13, 2018, 8AM-6PM, 50 Memorial Drive, Cambridge, MA

Reporter: Aviva Lev-Ari, PhD, RN

#CPCM2018 @AVIVA1950 @pharma_BI

 

 

Aviva Lev-Ari, PhD, RN, Editor-in-Chief, will attend and cover this event in REAL TIME for

 http://pharmaceuticalintelligence.com 


Over the past decade, there have been major advancements in the field of precision medicine, leading to exciting new treatments for some cancer patients. Much attention has been focused on genomic profiling of tumors to identify genomic alterations that might guide selection of specific therapies for individual patients. Beyond genomics, however, there is a variety of other precision approaches that can identify and exploit cancer-specific biological mechanisms including proteomics, metabolomics, and computational modeling, resulting in the more effective use of existing cancer medicines. On Thursday, December 13, 2018, the MIT Center for Precision Cancer Medicine will hold its inaugural annual symposium in the Samberg Conference Center at MIT. This full-day event will feature leading researchers and clinicians, who will highlight recent advances in precision cancer medicine and share perspectives on the future. An industry panel will also discuss the barriers to instituting precision medicine into current and future clinical trials.

 


Keynote Address

Charles Sawyers

Charles Sawyers, MD

Chair, Human Oncology and Pathogenesis Program
Memorial Sloan Kettering Cancer Center

Speakers

Andrea Califano

Andrea Califano, PhD

Clyde and Helen Wu Professor of Chemical Systems Biology, Columbia University
Chair, Department of Systems Biology, Columbia University
Director, JP Sulzberger Columbia Genome Center
Associate Director, Herbert Irving Comprehensive Cancer Center

Chris Love

J. Christopher Love, PhD

Professor of Chemical Engineering, MIT
Associate Member, Ragon Institute of MGH, MIT and Harvard
Member, Koch Institute, MIT

Richard Marais

Richard Marais, PhD

Professor of Molecular Oncology
Director, CRUK Manchester Institute
The University of Manchester

Kenna Mills Shaw

Kenna Mills Shaw, PhD

Executive Director
Sheikh Khalifa Bin Zayed al Nahyan Institute for Personalized Cancer Therapy
MD Anderson Cancer Center

Alice Shaw

Alice Shaw, MD, PhD

Professor, Harvard Medical School
Director, Thoracic Cancer Program, Massachusetts General Hospital

Matt Vander Heiden

Matthew Vander Heiden, MD, PhD

Associate Professor of Biology, MIT
Associate Director, Koch Institute
Member, MIT Center for Precision Cancer Medicine

Mike Yaffe

Michael B. Yaffe, MD, PhD

David H. Koch Professor of Science, MIT
Professor of Biology and Biological Engineering, MIT
Director, MIT Center for Precision Cancer Medicine
Director, Koch Institute Clinical Investigator Program

Jean Zhao

Jean Zhao, PhD

Professor of Biological Chemistry and Molecular Pharmacology
Harvard Medical School and Dana-Farber Cancer Institute


Panelists: Barriers to Instituting Precision Medicine in Clinical Trials

Hammerman

Peter Hammerman, MD, PhD

Global Head, Translational Research
Oncology Disease Area
Novartis Institutes for BioMedical Research

Ho

Steffan N. Ho, MD, PhD

Vice President, Head of Translational Oncology
Pfizer Global Product Development

Shiva Malek

Shiva Malek, PhD

Director and Principal Scientist
Department of Discovery Oncology
Genentech Inc

Marks

Kevin Marks, PhD

VP of Biology
Agios Pharmaceuticals

Michael Rothenberg

S. Michael Rothenberg, MD, PhD

Vice-President, Research and Development
Loxo Oncology, Inc.

Angela Koehler

Moderator:

Angela Koehler, PhD

Goldblith Career Development Professor in Applied Biology, MIT
Member, Koch Institute for Integrative Cancer Research
Member, MIT Center for Precision Cancer Medicine

 

Speakers:

Panelists:

  • Peter Hammerman, Novartis Institutes for BioMedical Research
  • Steffan Ho, Pfizer
  • Shiva Malek, Genentech, Inc
  • Kevin Marks, Agios Pharmaceuticals
  • S. Michael Rothenberg, Loxo Oncology, Inc

Moderated by Angela Koehler, MIT’s Koch Institute

Agenda:

8:00 am Registration and continental breakfast

8:45 am Opening remarks by Michael Yaffe (MIT’s Koch Institute)

  • Season of great expectation, tumor genetics is just the beginning, beyond: science, engineering, medicine: beyond genomics: immunology, cell biology, early detection, new drug development for the undrugable, system biology, RNAi
  • Jack Tyler was the initiator to find a donor for CPCM

9:00 am Keynote Address by Charles L. Sawyers (Memorial Sloan Kettering Cancer Center)

  • developed a drug for prostate cancer
  • Clinical trained oncologist/genomics
  • Lineage Plasticity:
  1. luminal cells in histology of origin and basal cells and require androgen receptor AR) function
  2. deprive lunimal cells fro growth factor
  3. Hormonal therapy Leuprolite, degarelix [castration methastatic]
  4. after relapse 2nd generation anti-androgens abirateron
  5. PING MU ENZALUTAMIDE RESISTANCE P53/RB! DELETION CONFER
  6. TRANSCRIPTION CHANGE: ANTIADROGEN RESISTANCE
  7. Lineage shift Sox2 level goes up – prevent drug resistance, in vivo and in vitro
  8. SOX2 promotes lineage placticity and antiadrogen resistance in TP53 and RBI-deficient prostate cancer
  9. Evolution of Lineage plasticity over time
  10. AR Pathway inhibition accelerates lineage plasticity: synaptophysin-positive disease in-vivo
  11. scRNA-seq time course – modeled by diffusion map displayed in luminal and basal cells
  12. Emergence of EMT phenotype, with retention of epithelial features
  13. Use CRISPR to perturb luminal plasticity by phyeno type
  14. Genomic landscape of Primary Prostate Cancer: ERG gain drives luminal layer
  15. Different classes of FOXA1 mutations in Prostate organoid Cancer – Missense, inframe, truncated
  16. FOXA1 key in hormone receptor signaling
  17. Hypermorphic peaks – ATAC-seq neomorphic FOXA1 pioneering activity
  18. Common Prostate Cancer Genes:differentiation phenotypes: TP53 Loss, RB1 – Loss,
  19. work of Matan Hofree – four subtypes of luminal cells
  20. involution and regeneration of single cell RNAseq
  21. Transcriptional shifts in response to castration/androgen addback
  22. androgen addback: 50% of luminal cells are proliferation in 48 hours
  23. cell responsible for organ regeneration

 

9:45 am Alice T. Shaw (Massachusetts General Hospital)

  • evolution of drug resistance in Lung Cancer
  • oncogenic drivers in lung adenocarcenoma –
  1. EGFR – sensitizing 19.4% of all patients
  2. KRAS
  3. ALK
  4. ROS1
  5. CMET
  6. BRAF
  7. NTRK1
  8. RET

Delay and prevention of drug resistance: liquid biopsy of pleural fluids and serial blood collections

  • Crizotinib patient with ROS1 + nsclc
  • acquired mutation in ROS1 G2032R – resistance to Crizotinib – Michael Lawrence, MGH – analysis of mutation and resistance
  • Repotrectinib – for ROS1 – Resistance mediated by this mutation
  • If patient fails three antiinhibitor drugs: secondary ALK mutations mediate Crizotinib Resistance
  • 2nd generation of  ALK inhibitors are structurally Distinct molecules
  • Lorlatinib – 3rd generation –>> back to 1st generation Crizotinib
  • Clonal evolution of resistance in ALK in NSCLC
  • compound mutations in ALK mutations – Lorlatinib Resistance
  • Sequential TKI therapy foster the development of compound mutation refractory to all generations og ALK TKIs – compound mutation can’t be overcome
  • Intratumoral Heterogeneity revealed by multiregion sequencing of renal cell carcinoma and resected NSCLC
  • somatic mutations: Pre-treatment to Lorlatinib resistance
  • Clonal Analysis: Multiple Drivers of resistance underlie clinical relapse
  • genomic instability – eradicate residual disease to eliminate drug resistance and tolerance persistance

 

10:25 am Networking Break

10:45 am Richard Marais (Cancer Research UK, Manchester Institute)

  • Melanoma – Precision Medicin
  • Request – NOT TO PUBLISH on the INTERNET, some of the work presented is not PUBLISHED.
  • Request is honored

11:25 am Matthew Vander Heiden (MIT’s Koch Institute)

  • Targeting Metabolism is altered in cancer
  • Metabolism is glucose carbohydrates, lipids – conversion of nutrients into biomass: ATP, Protein, Nucleic acid,
  • Not -proliferating cells vs proliferating cells
  • genetic mutations, tissue of origin, lineage of cells — metabolism takes place: combination of these three facto
  • environment consists the metabolic network definers.d by cell intrinsic network
  • Assessment of nutrient levels in tumor microenvironment
  • Metabolite analysis: ion suppression vs nutrients
  • nutrients are available to cells in tumors
  • depletion of glucose vs enrichment
  • metabolite most different: Gluthamine, needed for cancer to grow
  • Lineage can contribute – tryptophane and argenine
  • gluthamine – Cyctine affect gluthamine sensitivity to gluthamine inhibitors
  • what you eat, where is the tumor locate, tissue environment — more important
  • therapeutic window: metabolism processes – cell proliferation
  • ability to make aspartate – given to mice pancreatic  — tumor grow faster
  • cellular oxidation state correlate with pyruvate oxidation — PDH Activator suppress oxidation
  • Aspartate vs NAD+/NADH – lactate TCA – form more carbon
  • PDH activation reduces Redux
  • Serine availability can limit proliferation even in cells with increase
  • Serine vs NAD regeneration
  • which cancer falls into which group : Serine pathway – increase serine synthesis: Melanoma vs Breast cancer
  • growth of breast cancer: Serine availability dependent – accelerate of inhibit growth by level of serine
  • Model for how nutrient limitation affect tumor growth, tumor size depends of serine levels

 

12:05 pm Box lunch

12:30 pm Industry panel: Barriers to instituting precision medicine into clinical trials

  • Long term benefits of Precision Medicine
  • What phynotype are now looked for?

Michael Rothenberg

  1. short term, identify mutations
  2. more testing is needed
  3. sequencing the therapies
  4. challenge getting tissue, doing experiments in house
  5. Industry needs Academia collaboration for accelerated innovations
  6. AI may lower the cost of drug discovery

KEVIN MARX:

  1. MECHANISM OF RESISTANCE – COMBINATORIAL DRUG DISCOVERY
  2. phynotyping, tissue acquisition immune phenotype, what drive therapeutic response?
  3. genetic drivers
  4. HR seeks Scientistist that worked in TEAMS, collaborative science

STEPHAN HO

  1. long term benefits are very important
  2. Stage III disease – technology advances
  3. advanced in the regulatory space
  4. smaller cohort size to approve a drug
  5. biologic complexity, driver oncogenes, precision to imprecision
  6. cost of risk in investment in innovations
  7. check point inhibitor – known biology and immuno-modulation, data hypothesis and moving forward
  8. Organizational culture, interaction in teams, functional behavior
  9. commit to deliverable, perfect timing contingent on work of others.

Peter Hammerman

  1. single cell tumor immunity in combination drug therapy
  2. Tumor monitoring over time
  3. Novartis is interested to collaborate with innovators in Academia and in other institutions
  4. critical thinking on DATA and on negative data
  5. Combination drug therapy: orthogonal mechanism of actions and drug classed – toxicity is an issue

Shiva Malek

  1. How to drug mutations on DATA
  2. Acquired and intrinsic mutations
  3. exposure and patient safety
  4. UCSF’s Ashkenazi’s Team and Genetech – basic biology area selection
  5. Failure are not talked about
  6. Round table for problem solvers, how you approach a problem
  7. translational work require skills beyond technical expertise
  8. learning the navigation inside an organization
  9. leadership in R&D, expected to demonstrate leadership, the Scientist needs to have command of the field and of desirable directions of research

 

2:00 pm J. Christopher Love (MIT’s Koch Institute)

Acceleration of the PROCESS to develop Precision Medicine products

  • design, build, test – PROCESS
  • New drugs and vaccines – the process is iterative
  • measurements, with use of smallest number of samples
  • deliver precision medical: small f patients or large population or
  • clinical samples provide rich source of information: Blood or tissue sample
  • Tissue – extract RNA, component cells, single-cell RNA sequencing,
  • Challenges of enabling scRNA-seq in clinical labs
  • Probability, scale, capture efficiencies, temporal uniformity
  • single-cell sequencing
  • Seq-Well: method for scRNA-Seq
  • New Chemistries for T-cell
  • Blood: cell, cfDNA, Exosomes
  • map cancer genome from blood
  • Tissue:
  • Single circulating Tumor cells:
  • yield genomic landscape of cancer
  • cell free DNA, vells, proteins, metabolite, Tumor is existence, draw blood
  • cfDNA Tumor Fraction is prognostic of survival in mTNBC
  • automate to 13 cancer types
  • Rs is now possible
  • reduce sample requirement
  • cost is low digital information from clinical samples
  • Keytruda – is a molecular Signature
  • low volume product, advanced preparation (mo-years) __>>> agile solutions (days to years)
  • bentchtop, on-demand manufacturing system: Production, Purification, Formulation
  • hand-free production of formulated G-CSF: comparable to licensed products.
  • Plug and play manufacturing using  InSeq
  • Novel MAbs from patients
  • Many molecules to many products

 

2:40 pm Andrea Califano (Columbia University, System Biology)

Mechanistic Framework for the systematic pharmacological targeting of Non-Oncogene Dependencies – Precise Precision Oncology

  • systematic elucidation od critical cancer cell dependencies
  • drug MOA
  • Tumor dependencies to Drug MOA
  • Tumor heterogeneity
  • ARACNe – regulatory targets of regulatory proteins
  • Combinational Therapy: HER@ inhibitor and JAK1/JAK2 inhibitor
  • Driver Mutations
  • ARACNe; MINDy DIGGIT; Expression VIPER: MetaVIPER
  • Aberrantly activated protein for Prioritizing treatment in patients
  • Checkpoint activity reversal – prioritize drugs based on
  • Tumor model selection: GIST
  • 260 patients, 14 untreatable cancers — N of 1 Study
  • Single cell Studies – active proteins in stem-like progenitor cells
  • Ivermectin Treatment vs Control (7d vs 14d)

 

3:20 pm Networking Break

3:40 pm Jean Zhao (Dana Farber Cancer Institute)

Immunotherapy and Targeted Therapy in Cancer Therapy

  • Targeting cancer with CDK4/6 inhibitors
  • CDK4/6 inhibitors causes tumor regression in breast cancer and regression of CT-26 colorectal cancer
  • CDK4/6DNMT1 inducing viral mimicry
  • PARP inhibitors  changing treatment in ovarian cancer
  • FDA approved three drugs for ovarian cancer
  • p53-null; BRCA-null; myc high – model testing

 

4:20 pm Kenna Mills Shaw (MD Anderson Cancer Center)

  • PM nor a Silver bullet nor a Dream Illusion
  • 2013: not all mutations are equally actionable
  • Context of Biomarkers
  • co-mutations in lung cancer identity – therapeutic vulnerability
  • NGS cost decrease leads to increases in Data generation
  • there are only 125 genes ACTIONABLE IN THE CLINIC
  • finding biomarkers beyond direct targets
  • clinical actionability:80K mutation – 32%
  • patients: No standard treatment available
  • Enrollment inGenotype Matched TRIALS
  • MUTATIONS SCREENED: LACK OF ENROLLMENT NOT DUE TO LACK OF MATCHING PROCESS
  • 69% GOT NEW REGIMEN, 17% did not come back — no one called them
  • 58% enrolled on genotrype-matched trials
  • Beyond NGS:

www.personalizedcancertherapy.org

  • DECISION SUPPORT IN REAL TIME IMPROVES “MATCHING” TO RIGHT DRUG.
  • MULTIFACTORS: CO-MOEBIDITIES, MICROBIOME, IMMUNE PHYNOTYPING, GENOMICS, MICROBIOME, ZIP CODE, INFECTION

5:00 pm Michael Yaffe (MIT)

  • AUGMENTED SYNTHETIC LETHALITY
  • CANCER CELLS ARE UNDER CONSTANT STRESS
  • inflammation
  • Therpeutics-targeted Synthetic Lethality
  • BRCA mutation seen in 10%-20% of patients
  • p53 mutations DNA demage – leads to apoptosis p38 MK2 as a pathway is taking over repair DNA and no apotosis occurs.
  • doxorubicin
  • Nanoparticle targeting of siRNAs to established tumors
  • The Concept of augmented Synthetic Lethality   —- enhance a prevosly known synthetic interaction by targeting additional pathways
  • combination of repair pathway  and checkpoint activation – lead to better therapeutic results
  • MK2 – targets hnRNP A0 (an RNA binding protein)  – Cleaved Caspase 3 – is synthetic lethal with p53 mutuant tumors, not just p53 null alleles
  • MK2 links Inflammation and Cancer – IBD –>> polyps and Colon Cancer
  • myeloid cell recruitment to inflammatory tumors in
  • MK2 KO mice: IL-4 –M2 magrophage – tumor progression; regulate the tumor microenvironment
  • IFNgamma –>M1 macrophages – tumor suppression

 

 

 

SOURCE

https://ki.mit.edu/news/events/cpcmsymposium-2018

https://www.eventbrite.com/e/mit-center-for-precision-cancer-medicine-inaugural-symposium-tickets-50424019600?utm_campaign=event_reminder&utm_medium=email&utm_source=eb_email&utm_term=eventname

https://www.eventbrite.com/e/mit-center-for-precision-cancer-medicine-inaugural-symposium-tickets-50424019600

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CMS initiative in Modernizing Medicare to lead to Lower Prescription Drug Costs

Reporter: Aviva Lev-Ari, PhD, RN

 

CMS Takes Action to Lower Prescription Drug Costs by Modernizing Medicare

 

     

CMS Takes Action to Lower Prescription Drug Costs by Modernizing Medicare 
Proposed regulation for Medicare Parts C & D would strengthen negotiations with prescription drug manufacturers to lower costs and increase transparency for patients

Today, the Centers for Medicare & Medicaid Services (CMS) proposed polices for 2020 to strengthen and modernize the Medicare Part C and D programs. The proposal would ensure that Medicare Advantage and Part D plans have more tools to negotiate lower drug prices, and the agency is also considering a policy that would require pharmacy rebates to be passed on to seniors to lower their drug costs at the pharmacy counter.

“President Trump is following through on his promise to bring tougher negotiation to Medicare and bring down drug costs for patients, without restricting patient access or choice,” said HHS Secretary Alex Azar. “By bringing the latest tools from the private sector to Medicare Part D, we can save money for taxpayers and seniors, improve access to expensive drugs many seniors need, and expand their choice of plans. The Part D proposals complement efforts to bring down costs in Medicare Advantage and in Medicare Part B through negotiation, all part of the President’s plan to put American patients first by bringing down prescription-drug prices and out-of-pocket costs.”

In the twelve years since the Part D program was launched, many of the tools outlined in today’s proposal have been developed in the commercial health insurance marketplace, and the result has been lower costs for patients. Seniors in Medicare also deserve to benefit from these approaches to reducing costs, so today CMS is proposing to modernize the Medicare Advantage and Part D programs and remove barriers that keep plans from leveraging these tools.

“In designing today’s proposal, foremost in the agency’s mind was the impact on patients, and the proposal is yet another action CMS has taken to deliver on President Trump and Secretary Azar’s commitment on drug prices,” said CMS Administrator Seema Verma. “Today’s changes will provide seniors with more plan options featuring lower costs for prescription drugs, and seniors will remain in the driver’s seat as they can choose the plan that works best for them. The result will be increasing access to the medicines that seniors depend on by lowering their out-of-pocket costs.”

Private plan options for receiving Medicare benefits are increasing in popularity, with almost 37 percent of Medicare beneficiaries expected to enroll in Medicare Advantage in 2019, and Part D enrollment increasing year-over-year as well. The programs are driven by market competition; plans compete for beneficiaries’ business, and each enrollee chooses the plan that best meets his or her needs. Consumer choice puts pressure on plans to improve quality and lower costs.  Premiums in both Medicare Advantage and Part D are projected to decline next year.

Today’s proposed changes include:

  • Providing Part D plans with greater flexibility to negotiate discounts for drugs in “protected” therapeutic classes, so beneficiaries who need these drugs will see lower costs;
  • Requiring Part D plans to increase transparency and provide enrollees and their doctors with a patient’s out-of-pocket cost obligations for prescription drugs when a prescription is written;
  • Codifying a policy similar to the one implemented for 2019 to allow “step therapy” in Medicare Advantage for Part B drugs, encouraging access to high-value products including biosimilars; and
  • Implementing a statutory requirement, recently signed by President Trump, that prohibits pharmacy gag clauses in Part D.

CMS is also considering for a future plan year, which may be as early as 2020, a policy that would ensure that enrollees pay the lowest cost for the prescription drugs they pick up at a pharmacy, after taking into account back-end payments from pharmacies to plans.

Medicare Advantage and Part D will continue to protect patient access, as both programs are embedded with robust beneficiary protections. These include CMS’s review of Part D plan formularies, an expedited appeals process, and a requirement for plans to cover two drugs in every therapeutic class.

CMS looks forward to receiving comments on these proposals and other policies under consideration.

For a blog post on the proposed rule by Secretary Azar and Administrator Verma, please visit: https://www.cms.gov/blog/proposed-changes-lower-drug-prices-medicare-advantage-and-part-d.

For a fact sheet on the proposed rule, please visit: https://www.cms.gov/newsroom/fact-sheets/contract-year-cy-2020-medicare-advantage-and-part-d-drug-pricing-proposed-rule-cms-4180-p.

The proposed rule (CMS-4180-P) can be downloaded from the Federal Register at: https://s3.amazonaws.com/public-inspection.federalregister.gov/2018-25945.pdf

###

Get CMS news at cms.gov/newsroom, sign up for CMS news via email and follow CMS on Twitter CMS Administrator @SeemaCMS

SOURCE

https://www.cms.gov/newsroom/press-releases/cms-takes-action-lower-prescription-drug-costs-modernizing-medicare?mc_cid=ca8901d1c5&mc_eid=32328d8919

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Cardiovascular (CV) Disease and Diabetes: New ACC Guidelines for use of two major new classes of diabetes drugs — sodium-glucose cotransporter type 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) for reduction of adverse outcomes

Reporter: Aviva Lev-Ari, PhD, RN

Updated on 10/24/2022

Diabetes Becoming Less Potent Risk Factor for CVD Events

Richard Mark Kirkner

Shift in Practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Ke said.

Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Ke and Deedwania have no relevant financial relationships to disclose.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

SOURCE

https://www.medscape.com/viewarticle/982801

 

October 20, 2022

“The main aim for this report is to educate cardiologists, who might not otherwise think about prescribing diabetes drugs, about these two new classes of medications that have important cardiovascular benefits for their patients,” cochair of the writing committee for the new consensus document, Brendan Everett, MD, assistant professor of medicine, Brigham and Women’s Hospital, Boston, commented to theheart.org | Medscape Cardiology.

We hope to help them understand which of their patients might benefit, and to help them understand how to prescribe these new drugs appropriately to their patients with both atherosclerotic cardiovascular disease and diabetes.”

The document is published online November 26 in the Journal of the American College of Cardiology, and is endorsed by the American Diabetes Association.

Journal of the American College of Cardiology

2018 ACC Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease

A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways Writing Committee: 

4 Pathway Summary Graphic

Figure 1 provides an overview of what is covered in the Expert Consensus Decision Pathway. See each section for more detailed considerations and guidance.

” data-icon-position=”” data-hide-link-title=”0″>Figure 1

Figure 1

Summary Graphic

Figure 2 offers 1 approach to deciding which drug to use in which patient, Table 11 outlines patient and clinician preferences to consider when selecting an SGLT2 inhibitor or GLP-1RA. Table 12 provides an overview of considerations for initiating and monitoring an SGLT2 inhibitor. Table 13 provides an overview of considerations for initiating and monitoring a GLP-1RA.

Figure 2

Approach to Managing Patients With Established ASCVD and T2D

SOURCE

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Precision Medicine Market to surpass USD 96.6 Bn by 2024, study by Global Market Insights, Inc.

Reporter: Aviva Lev-Ari, PhD, RN

 

Precision Medicine Market to surpass USD 96.6 Bn by 2024

The Precision Medicine Market is set to grow from its current market value of more than $47.8 billion to over $96.6 billion by 2024; as reported in the latest study by Global Market Insights, Inc.

Advancements in cancer biology will ensure development in gene sequencing technique and other platforms available for cancer treatment. Furthermore, rising development in field of bioinformatics that support gene sequencing to initiate formulations of precision medicines will enhance the precision medicine market growth in foreseeable future.

Increase in adoption rate of gene therapy in developed economies with relatively high-income level will further enhance the precision medicine market growth. Rising incidences of genetic disorders has positively influenced the business growth. According to WHO, sickle cell anemia affects around millions of people globally every year. Along with sickle cell anemia, there are many other genetic diseases such as thalassemia, hemophilia and others that are prevalent globally. Moreover, increase in research and development activities that boosts the production and manufacturing of precision medicine in emerging countries such as Africa and Brazil will augment the industry growth in future. However, high cost of precision medicines may restrain the market growth.

Precision Medicine Market

 

 

Bioinformatics segment was valued at USD 7.4 billion in 2017 and is expected to have considerable growth during the forecast timeframe. Bioinformatics is composed of information that includes data for gene sequencing, amino acid sequences of proteins and structural classification of protein enabling efficient drug development process for treating diseases such as cancer at molecular level. Additionally, bioinformatics is also used to determine the treatment for hereditary metabolic disorders that will drive the segmental growth in forthcoming years.

Oncology segment will experience 11.1% CAGR during the forecast timeframe. High segmental growth can be attributed to the increasing prevalence of cancer globally. According to Globocan 2018, the number of new cancer cases are estimated to be 18.1 million cases. Development of target novel therapies and precision medicines has drastically reduced the mortality rates and hence, high demand for precision medicine in cancer treatment will drive the segmental growth in foreseeable future.

Pharmaceutical companies segment of precision medicine market accounted for 37.1% in 2017 owing to the increasing R&D efforts for drug development activities. Pharmaceutical companies are currently trying to develop precision medicines for rare genetic diseases. According to Global genes, there are around 7,000 rare genetic diseases discovered.

U.S. precision market will experience 9.7% CAGR during the forecast timeframe. Enormous market growth will be due to increasing cases of rare genetic diseases. Furthermore, certain initiatives undertaken by the regulatory bodies have also positively impacted availability of precision medicines.

U.S. Precision Medicine Market Size, By Technology, 2017 & 2024 (USD Million)

Germany precision medicine market was valued at USD 2.6 billion in 2017 and high segmental growth will be due to the growing pediatric as well as adult population susceptible to metabolic diseases such as diabetes. According to NCBI, prevalence of Type 2 diabetes is high in the German population. Researchers and scientists have geared up efforts to develop precision medicines that are altered according to patient’s genome ensuring efficient treatment of genetic disorders.

Prominent industry players operational in the precision medicines market include Biocrates Life Sciences AG, Eagle Genomics Ltd, Ferrer inCode, Intomics, Laboratory Corporation of America Holdings, NanoString Technologies, Novartis, Pfizer, Qiagen, Quest Diagnostics, F. Hoffmann-La Roche, Silicon Biosystems, Tepnel Pharma Services, Teva Pharmaceuticals.

Source: https://www.gminsights.com/industry-analysis/precision-medicine-market

 

SOURCE for Request to Publish in pharmaceuticalintelligence.com

From: Shankar Khatkale <shankar.k@gminsights.com>

Date: Tuesday, November 27, 2018 at 6:48 AM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Article Submission Request

Dear Editor,

An industry news titled ‘Precision Medicine Market Size worth $96.6bn by 2024’ by Global Market Insights is relevant to your esteemed website https://pharmaceuticalintelligence.com. This email is a suggestion to publish this news (content attached in word format or can be picked from link mentioned below) on your website with an objective to share the information with your audiences.

News Link: https://www.gminsights.com/pressrelease/precision-medicine-market

Looking forward to hear from you.

On behalf of and as instructed by Global Market Insights, Inc.

Best Regards,

Shankar Khatkale |SEO Executive

 

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Jennifer Doudna and NPR science correspondent Joe Palca, several interviews

Reporter: Aviva Lev-Ari, PhD, RN

2.1.3.5

2.1.3.5   Jennifer Doudna and NPR science correspondent Joe Palca, several interviews, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

UPDATED on 11/27/2018

SAVE

The ethical red flags of genetically edited babies

Driving the news: Chinese scientist He Jiankui announced Sunday night that a pair of twin girls had been born from embryos he modified using the gene-editing tool known as CRISPR.

  • He hasn’t provided solid proof, but if it‘s true, it would be the first time the technology has been used to engineer a human.

What they’re saying: The inventors of CRISPR technology did not seem pleased with the development — one called for a moratorium on implantation edited embryos into potential mothers.

  • “I hope we will be more cautious in the next thing we try to do, and think more carefully about when you should use technology versus when you could use technology,” said Jessica Berg, a bioethicist at Case Western Reserve University.

Between the lines: Several specific factors in He’s work sent up ethical red flags.

  • Many scientists had assumed that, when this technology was first used in humans, it would edit out mutations tied to a single gene that were certain to cause a child pain and suffering once it was born — essentially, as a last resort.
  • But He used CRISPR to, as he put it, “close a door” that HIV could have one day traveled through. That has prompted some speculation that this project was more about testing the technology than serving an acute medical need.
  • “That should make us very uneasy about the whole situation,” Berg said. “Of all the things to have started with, it does make you a little suspicious about this particular choice.”

The intrigue: There’s a lot we still don’t know about He’s work, and that’s also contributing to an attitude of skepticism.

  • How many embryos did he edit and implant before these live births?
  • How will he know it worked? As the children age, they’ll likely have their blood drawn and those samples will be exposed to HIV in a lab, but researchers aren’t going to tell them to go out and have unprotected sex or use intravenous drugs — another reason HIV seems like an odd starting place for human gene editing.
  • How did this even happen? The university where He worked said he was on leave, and Chinese officials have said he’s under investigation. But gene editing is a pretty hard thing to freelance.

The other side: He defended his work in a video message, saying, “I understand my work will be controversial but I believe families need this technology and I’m willing to take the criticism for them.”

  • “Their parents don’t want a designer baby, just a child who won’t suffer from a disease which medicine can now prevent,” He said.

Yes, but: Now that this threshold may have been crossed, attempts to create “designer babies” — within the limitations of what CRISPR can do — probably aren’t far off, some experts fear.

  • There are “likely to be places that are less regulated than others, where people are going to attempt to see what they can do,” Berg said. “I wouldn’t say everything in the world has changed now, but it’s certainly the next step.”
SOURCE

https://www.axios.com/genetic-editing-baby-china-ethics-controversy-b33f8414-8b83-445c-bad5-d8407f8841f4.html

UPDATED on 11/26/2018

  1. CRISPR pioneer Jennifer Doudna explains gene-editing …

    news.harvard.edu/gazette/story/2018/05/crispr…

    Doudna, who spoke at Harvard’s Science Center, explained the work that led to the development of CRISPR/Cas9 geneediting technology, which was described in a paper in the journal Science in 2012. A sign of how quickly the techniques would be adopted by her scientific colleagues came within months.

  2. Eventbrite – Science History Institute presents Jennifer A. Doudna, “CRISPR Biology and Biotechnology: the Future of Genome Editing” – Friday, November 16, 2018 at Science History Institute, Philadelphia, PA.

  3. A pioneer of the Crispr geneediting technology that’s taken Wall Street by storm says the field is probably five to 10 years away from having an approved therapy for patients.

  4. A Crack in Creation: Gene Editing and the Unthinkable Power …

    thehumanist.com/magazine/november-december-2017/…

    BOOK BY JENNIFER DOUDNA AND SAMUEL STERNBERG HOUGHTON MIFFLIN HARCOURT, 2017 304 PP.; $28.00 (HARDCOVER) $14.99 (KINDLE) CRISPR is the basis of a genome editingtechnology—the latest breakthrough in the grand tradition that began over 400 generations ago when we started to grow wheat and rice instead of just picking its wild cousins.

  5. The CRISPR-Cas9 gene editing technology was discovered in 2012 by campus professor of chemistry, molecular biology and biochemistry Jennifer Doudna and Emmanuelle Charpentier, director at the Max …

  6. 2 hours ago · The International Summit on Human Genome Editing begins here on Tuesday and many researchers, ethicists, and policymakers attending the meeting first learned of He’s claim through media reports.

Video of Conversation With Jennifer Doudna and NPR’s Joe Palca

WATCH VIDEO

https://today.lbl.gov/2018/01/26/video-of-conversation-with-jennifer-doudna-and-nprs-joe-palca/

Published on Jan 24, 2018

SUBSCRIBE 13K
This conversation between Berkeley Lab researcher Jennifer Doudna and NPR science correspondent Joe Palca took place on on Monday, Nov. 20, 2017. The event was the first in the Director’s Distinguished Women in Science speaker series, a venue for women scientists to share their work and perspectives with the Lab community. Instagram: https://www.instagram.com/berkeleylab/ Twitter: https://twitter.com/berkeleylab Facebook: https://www.facebook.com/BerkeleyLab/ More Berkeley Lab news: http://bit.ly/BerkeleyLabNews Subscribe: https://youtube.com/berkeleylab
SOURCE

Jennifer Doudna Talks CRISPR Origins, Implications with NPR’s Joe Palca

SOURCE

http://biosciences.lbl.gov/2017/12/01/jennifer-doudna-talks-crispr-origins-implications-nprs-joe-palca/

Jennifer Doudna featured on NPR’s Morning Edition for her work on CRISPR/Cas9 — a tool for editing genes

October 13, 2014
Jennifer Doudna. Jennifer Doudna. Photo: Roy Kaltschmidt, Berkeley Lab Public Affairs

UC Berkeley’s Jennifer Doudna was featured on NPR’s Morning Edition for her work on CRISPR/Cas9 — a tool for editing genes. Jennifer Doudna and her colleagues showed that CRISPR/Cas9, can be used with great precision to selectively disable or add several genes at once in human cells, offering a potent new tool to understand and treat complex genetic diseases.

Read more and listen to the full story, “In Hopes Of Fixing Faulty Genes, One Scientist Starts With the Basics.”

SOURCE

https://vcresearch.berkeley.edu/news/jennifer-doudna-featured-nprs-morning-edition-her-work-crisprcas9-tool-editing-genes

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VIDEO: Editor’s Choice of the Most Innovative New Cardiac Technology at AHA 2018

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Heart Murmur Detection done by AI Algorithm (Eko Core and Eko Duo) Devices Outperform most Auscultatory Skills of Cardiologists

Reporter: Aviva Lev-Ari, PhD, RN

 

AI Algorithm Outperforms Most Cardiologists in Heart Murmur Detection

Eko’s heart murmur detection algorithm outperformed four out of five cardiologists in recent clinical study

“Artificial Intelligence Detects Pediatric Heart Murmurs With Cardiologist-Level Accuracy,” the study demonstrates the power of machine learning and artificial intelligence (AI) to enhance cardiac care.

The neural network AI algorithm was trained on thousands of heart sound recordings. The algorithm was then tested on an independent dataset of pediatric heart sounds and compared to gold-standard echocardiogram imagery. Five pediatric cardiologists also listened to the heart sound recordings and independently made a determination whether a recording contained a murmur. This advancement will help narrow the clinical skill gap between the 27,000 cardiologists in the U.S. — the experts at murmur detection — and the 3.8 million other clinicians who are less experienced in the identification of heart murmurs through a stethoscope.

A study published in the Journal of the American Medical Association revealed that, on average, internal medicine and family practice physician residents misdiagnose 80 percent of common cardiac events.1 Cardiologists on the other hand, can effectively diagnose 90 percent of cardiac events using a stethoscope.2

Eko’s murmur screening algorithm, when coupled with the company’s U.S. Food and Drug Administration (FDA)-cleared Eko Core and Eko Duo devices, will enable any and all clinicians to more accurately screen for heart murmurs.

Eko is currently pursuing FDA clearance for the algorithm and will be rolling it out with its existing cardiac monitoring devices upon securing regulatory clearance.

For more information: http://www.ekohealth.com

References

1. Mangione S., Nieman L.Z. Cardiac auscultatory skills of internal medicine and family practice trainees. A comparison of diagnostic proficiency. Journal of the American Medical Association, Sept. 3, 1997. doi:10.1001/jama.1997.03550090041030

2. Thompson W.R. In defence of auscultation: a glorious future? Heart Asia, Feb. 1, 2017. doi:  [10.1136/heartasia-2016-010796]

 

SOURCE

https://www.dicardiology.com/content/ai-algorithm-outperforms-most-cardiologists-heart-murmur-detection?eid=333021707&bid=2308309

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Tweeter and Real Time Conference Press Coverage: Aviva Lev-Ari, PhD, RN
  1. LIVE eProceeding Day Two – The 14th Annual Personalized Medicine Conference: The Business of Personalization, November 15, 2018, HMS, Boston via

  2. Cary Pfeffer, M.D., Partner, Third Rock Ventures IP can’t be reduced by other country unfair trade

  3. Pellini – CMS will take the lead partnerships early and often in clinical trials,

  4. Michael Pellini, M.D., Managing Partner, Section 32; Board Member, Personalized Medicine Coalition Patients and Consumers will force in five years figuring out – every diagnosis of cancer will be sequenced to interpret results and paid for

  5. Salveen Richter, Goldman Sachs Sequencing cost plunged, public investors placing funding in start ups even without return in the horizon, companies with multiple modalities spurring innovation – Europe vs US, China has no FDA ,talent from US China

  6. Michael Pellini, M.D., Managing Partner, Section 32; Board Member, Personalized Medicine Coalition Diagnostics component inside 4.8 Trillion in the therapeutics selection in the system as a whole Foundation Medicine saw Roche for International reach

  7. William A. Sahlman, Ph.D., Baker Foundation Professor, Harvard Business School Biotech IPO, VC, windows slam shut, drug failure – drivers and non Increasing return to scale: AI, NGS, screening, – foreign money, Tsinghua went back to China from CA

  8. William A. Sahlman, Ph.D., Baker Foundation Professor, Harvard Business School market – can it sustain the opportunity – winners and losers innovative financial models Biotech IPO, VC, windows slam shut, drug failure – drivers and non

  9. Salveen Richter, C.F.A., Vice President, Research Division, Goldman Sachs Europe successful in financing Health care in the US system must change – investment will flee, to fund pricing drug is key in changing the system CART Pricing is key

  10. Michael Pellini, M.D., Managing Partner, Section 32; Board Member, Personalized Medicine Coalition Impasse or Inflection Point? it s Inflection Point NOT an Impasse Diagnostics component inside 4.8 Trillion in the therapeutics selection in system

  11. Cary Pfeffer, M.D., Partner, Third Rock Ventures MS drug efficacy was in 50% non respondents 25% Genomic sequencing to identify patient populations – target therapy Mayocardia – drug in CVD for patients identified by Genomics Genomics develop drugs

  12. Michael Pellini, M.D., Managing Partner, Section 32; Board Member, Personalized Medicine Coalition Impasse or Inflection Point? it s Inflection Point NOT an Impasse

  13. Kristine Bordenave, M.D., F.A.C.P., Corporate Medical Director, Humana CMS Guideline: every test ordered must guide treatment otherwise not covered

  14. Kristine Bordenave, M.D., F.A.C.P., Corporate Medical Director, Humana Guidelines on ordering genomic testing, AI can assist providers, MDs need to catch up on a weekly basis companion diagnostics and pharmaceutical paid together SOCare is paid

  15. Kristine Bordenave, M.D., F.A.C.P., Corporate Medical Director, Humana show us any value as good value – avoiding patient going to MDs Office, Hospital, ER – cost increase due to Pharmacogenomics testing $5K per test

  16. Scott Ramsey, M.D., Ph.D., Full Member, Fred Hutchinson Cancer Research Center; Director, Hutchinson Institute for Cancer Outcomes Research Pricing of Testing NGS and Targeted therapy represent a threat to adoption of Genomics in Medicine

  17. Kristine Bordenave, M.D., F.A.C.P., Corporate Medical Director, Humana What test needed to be ordered? Patient stay healthy NGS $650 – $2000 in 2018, in 2016 it was $25,000 cost of testing, cost of drugs

  18. Kristine Bordenave, M.D., F.A.C.P., Corporate Medical Director, Humana cost of doing the test vs not doing this test – assess value CMS – provide data on what is covered and what is not Humana: any missed opportunities, MD order tests of no impact MR

  19. Dr. Ramsey – Survival in this cohort NGS vs EGFR – improved survival 6 month longer, Increased survivals, why? cost of sequencing – #14 most influential – cost does not drive value #1 drug cost, out of pocket expense was the factor #2 survival

  20. Scott Ramsey, M.D., Ph.D., Full Member, Fred Hutchinson Cancer Research Center; Director, Hutchinson Institute for Cancer Outcomes Research Value and utility are interconnected cost effectiveness of NGS in melanoma: single gene testing, EGFR vs NGS

  21. Kristine Bordenave, M.D., F.A.C.P., Corporate Medical Director, Humanalabs, payers, providers, pharma — the GAP to be bridged opportunities to prevent and treat disease Payers, MDs, cost and impact, markers, Humana has a research division Use Tests

  22. MODERATOR | Daryl Pritchard, Ph.D., Senior Vice President, Science Policy, Personalized Medicine Coalition genetic profiling, adopt policy for mass deployment of NGS demonstrate value, payers needs little more that evidence exist for payer to cover

  23. Luba Greenwood, J.D., Strategic Business Development and Corporate Ventures, Verily (an Alphabet company) Patient need to own the genome data not a Databank

  24. Birgit Funke, Ph.D., F.A.C.M.G., Vice President, Clinical Affairs, Veritas Genetics; Associate Professor of Pathology (Part-Time), Harvard Medical School Risk prevention, driving DOWN operating cost curation of the Genome

  25. Luba Greenwood, J.D., Strategic Business Development and Corporate Ventures, Verily (an Alphabet company) Diagnostics in use to keep patients OUT of hospitals – management of chronic diseases

  26. Luba Greenwood, J.D., Strategic Business Development and Corporate Ventures, Verily (an Alphabet company) treatment solution therapeutics except og Oncology threatment is a strugle in the genomics field and pharmacogenomics General Medicine: CVD DM

  27. Keith Stewart, M.B., CH.B., Carlson and Nelson Endowed Director, Center for Individualized Medicine, Mayo Clinic genomics for detection of predisposition, inherited Barriers to deploy genomics: Knowledge, readiness of providers, cost of uninsured,

  28. Ellen Sigal Recipient of 14th PMC Award

  29. Sigal: Patient deserve right answers right choices, calls doctors on behave of patients treatments done out of the community in Academic hospitals – patients are scared to death. Patients are asking for options: Right testing, access to testing

  30. The 14th Annual Leadership in Personalized Medicine Award to Ellen V. Sigal, Ph.D., Chairperson, Founder, Friends of Cancer Research Patient Challenges: 90% are treated Community and they need a second opinion, insurance, access, clinical trials

  31.  Retweeted

    Frederick Banting, awarded the Nobel Prize for the discovery of insulin, was born on this day in 1891. The discovery of insulin is one of the biggest breakthroughs in medicine and has saved millions of lives.

  32. Amy Abernethy, M.D., Ph.D., Chief Medical Officer, Chief Scientific Officer, Senior Vice President, Oncology, Flatiron Health Technologies: AI, Countries with platforms Regulatory framework, reproducibility of results Taking care of people,

  33.   Retweeted

    I am covering this Conference at Harvard Medical School in Real Time, 11/14-11/15/2018 ⁦

  34. Edward Tepporn, Executive Vice President, Asian & Pacific Islander American Health Forum 1985 minorities education all surveys conducted in English, Asian American access to affordable health care services to accommodate services for communities

  35. Adolph P. Falcón, Executive Vice President, National Alliance for Hispanic Health community based organization 50 million improving healthcare access improve inclusion in science, no advancement in 45 years Hard to reach through – academic language

  36. Alex J. Carlisle, Ph.D., Chairman, CEO, National Alliance Against Disparities in Patient Health PM with focus on disparities, racialbiologic, socioecological Patient centered – raise health education Translation for interpretation Physicians&Patients

  37. Vence L. Bonham, Jr., J.D., Senior Advisor, Director on Genomics and Health Disparities, U.S. NHGRI Genomics data is of European dissents no diversity minority populations not represente sland populations not represented hispanics not

  38. Kimberly Popovits, proprietary test vs. test offered by all labs — different markets Utility agreed upon like “” demonstrate a pathway of product development that was already followed

  39. Kimberly Popovits, Chairman of the Board, CEO, President, Genomic Health – Oncology, Breast cancer molecular diagnostics Genomic testing saved the Health care System billions of dollars Genomic testing will not be placebo, 12 years study controlled

  40. Julie Khani, President, American Clinical Laboratory Association FDA will establish a center for Diagnostics, proposal for pre-certification like in Medical devices congress is involved in the decision making

  41. Michael Doherty, Senior Vice President, Head of Product Development, Head of Research & Development, Foundation Medicine – ex Genetech/Roche Operate in regulated environment, how to establish a company for long term companion diagnostics

  42. Joseph V. Ferrara, CEO, Boston Healthcare Associates Regulatory action for reimbursement of test new categories of tests: new payment if Innovation, PLA codes, 45 months approval, CPT codes

  43. Best Talk like last year by David King , keynote at

  44. David King, J.D., Chairman, CEO, LabCorp Non respondent – further researched MDs understanding, confidence of results PM Promise: close education GAP, convene on VALUE for individual cases not populations assess value among initiatives PM

  45. Tom Miller, Managing Partner, GreyBird Ventures LLC algorithms are behind the firewall of the Hospital, for privacy. the patient’s identity is not of central point, privacy is the key

  46. Radiology: SW used in detection of disease Personalized Medicine and AI Data mining of Text using AI Vital signs monitoring – providers can spot Arrhythmias earlier tagging images is a matual process

  47. Darrell M. West, Ph.D., Vice President of Governance Studies and Director of Center for Technology Innovation, Douglas Dillon Chair in Governance Studies, Interest in AI and in particular: Health care large part of the economy

  48. Gregg Talbert, Ph.D., Global Head of Digital and Personalized Health Care Partnering, Roche – Data on mutations Data falls short on Patient follow up (longitudinal data on Patients) curation of EMR IS NOT AN EASY OR AUTOMATED PROCESS i.e., IMAGES

  49. Tom Miller, Managing Partner, GreyBird Ventures LLC AI applied to capture unusual movement allowing to detect a forthcoming neurological event. Technologies used now

  50. Colin Hill, Chairman, CEO, Co-Founder, GNS Healthcare is moderator for and Medicine, panelists from , and The ⁦⁩ ⁦⁩ ⁦

  51. Bryce Olson, Global Marketing Director, Health and Life Sciences Group, Intel Corporation; stage IV prostate cancer patient Patient engage in their care, involvement in interpretation og ONES OWN Genome sequence is ate most engaging

  52. Emily Kramer-Golinkoff, Co-Founder, Emily’s Entourage, cystic fibrosis patient “Better for a is the Patient him/herself”

  53. Great Panel moderation by Toni Andreu scientific director of

  54.   Retweeted

    can help cancer patients live longer, healthier lives. Learn more about how we’re working to advance the field ‘s 11/15 when Ellen Sigal receives the 14th Annual Leadership in Personalized Medicine Award:

  55. Enjoyed most learning about the leading evolution in Genomics in Israel, UK, Canada and Finland

  56.   Retweeted

    In 14th Annual Elizabeth Nabel- made an excellent overview exploring the Promise of Personalized Medicine: Healthcare state-of-the-art; Digital health; Professionals-Payers-Providers relationships and next future challenges

  57. Amazing International Panel: UE, Israel, UK, Canada, Finland

  58. Great talk of a visionary in Management of Academic

  59. Great Confernec, 14th in one row

  60. Antonio L. Andreu, M.D., Ph.D., Scientific Director, EATRIS European Infrastructure for Translational Medicine General Medicine: Metabolomics, biological systems vs GENOMICS Medical care w/genomic testing, MDs will call to tell patients future news

    Translate Tweet

  61. Ora Dar, Ph.D., Senior Expert, Medical Sciences, consultant to the Israel Innovation Authority $300Miliion R&D sponsored clinical data on genomics, MDs are trained to place genomics data on EMR, epidemiology, sequencing of genetic diseases

  62. Liisa-Maria Voipio-Pulkki, M.D., Ph.D., Director General, Chief Medical Officer, Ministry of Social Affairs and Health, Finland Public sector is the majority of Health care systems, Expertise is as high as can be, entrepreneurship is on the rise

  63. Marc LePage, President, CEO, Genome Canada Social impact, adoption systems for focusing on rare diseases, following UK and US trends, 10 sites in Canada, aggregate the datethe National level, extract clinical data securely implementation expertise

  64. Tom Fowler, Ph.D., Deputy Chief Scientist, Building infrastructure, education, future, National approach to genomic testing, built in a National lab, scaling research

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Once herpes simplex infects a person, the virus goes into hiding inside nerve cells, hibernating there for life, periodically waking up from its sleep to reignite infection, causing cold sores or genital lesions to recur. Research from Harvard Medical School showed that the virus uses a host protein called CTCF, or cellular CCCTC-binding factor, to display this type of behavior. Researchers revealed with experiments on mice that CTCF helps herpes simplex regulate its own sleep-wake cycle, enabling the virus to establish latent infections in the body’s sensory neurons where it remains dormant until reactivated. Preventing that latency-regulating protein from binding to the virus’s DNA, weakened the virus’s ability to come out of hiding.

 

Herpes simplex virus’s ability to go in and out of hiding is a key survival strategy that ensures its propagation from one host to the next. Such symptom-free latency allows the virus to remain out of the reach of the immune system most of the time, while its periodic reactivation ensures that it can continue to spread from one person to the next. On one hand, so-called latency-associated transcript genes, or LAT genes, turn off the transcription of viral RNA, inducing the virus to go into hibernation, or latency. On the other hand, a protein made by a gene called ICP0 promotes the activity of genes that stimulate viral replication and causes active infection.

 

Based on these earlier findings, the new study revealed that this balancing act is enabled by the CTCF protein when it binds to the viral DNA. Present during latent or dormant infections, CTCF is lost during active, symptomatic infections. The researchers created an altered version of the virus that lacked two of the CTCF binding sites. The absence of the binding sites made no difference in early-stage or acute infections. Similar results were found in infected cultured human nerve cells (trigeminal ganglia) and infected mice model. The researchers concluded that the mutant virus was found to have significantly weakened reactivation capacity.

 

Taken together, the experiments showed that deleting the CTCF binding sites weakened the virus’s ability to wake up from its dormant state thereby establishing the evidence that the CTCF protein is a key regulator of sleep-wake cycle in herpes simplex infections.

 

References:

 

https://www.ncbi.nlm.nih.gov/pubmed/29437926

 

https://hms.harvard.edu/news/viral-hideout?utm_source=Silverpop

 

https://www.ncbi.nlm.nih.gov/pubmed/30110885

 

https://www.ncbi.nlm.nih.gov/pubmed/30014861

 

https://www.ncbi.nlm.nih.gov/pubmed/18264117

 

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