Monthly Archives: June 2017

A core assumption in the study of disease-causing genes has been that they are clustered in molecular pathways directly connected to the disease. But work by a group of researchers at the Stanford University School of Medicine suggests otherwise.

The gene activity of cells is so broadly networked that virtually any gene can influence disease, the researchers found. As a result, most of the heritability of diseases is due not to a handful of core genes, but to tiny contributions from vast numbers of peripheral genes that function outside disease pathways.

Any given trait, it seems, is not controlled by a small set of genes. Instead, nearly every gene in the genome influences everything about us. The effects may be tiny, but they add up.

The work is described in a paper published June 15 in Cell. Jonathan Pritchard, PhD, professor of genetics and of biology, is the senior author. Graduate student Evan Boyle and postdoctoral scholar Yang Li, PhD, share lead authorship.

The researchers call their provocative new understanding of disease genes an omnigenic model to indicate that almost any gene can influence diseases and other complex traits. In any cell, there might be 50 to 100 core genes with direct effects on a given trait, as well as easily another 10,000 peripheral genes that are expressed in the same cell with indirect effects on that trait, said Pritchard, who is also a Howard Hughes Medical Institute investigator.

Each of the peripheral genes has a small effect on the trait. But because those thousands of genes outnumber the core genes by orders of magnitude, most of the genetic variation related to diseases and other traits comes from the thousands of peripheral genes. So, ironically, the genes whose impact on disease is most indirect and small end up being responsible for most of the inheritance patterns of the disease.

This is a compellingpaper that presents a plausible and fascinatingmodel to explain a number of confusing observations from genomewide studies of disease, said Joe Pickrell, PhD, an investigator at the New York Genome Center, who was not involved in the work.

Until recently, said Pritchard, he thought of genetically complex traits as conforming to a polygenic model, in which each gene has a direct effect on a trait, whether that trait is something like height or a disease, such as autism.

See the rest here:
Thousands of genes influence most diseases - Stanford Medical Center Report

While much of the excitement surrounding precision medicine focuses on using genomics to tailor personalized treatment plans, speakers at the Precision Medicine Summit said theres more to it.

We cannot achieve precision medicine without having everyone be a participant and benefit and understand, said India Barnard-Hook, director of strategy and associate director of precision medicine at University of California, San Francisco. Precision medicine is about much more than genomics.

Social determinants of health, for instance, typically occur outside the healthcare system and have a significant impact on both health and individual outcomes.

You have to know a lot more than the clinical phenotype, said Linda Chin, chief innovation officer for health affairs at The University of Texas Health System.If you understand all the other factors that contribute to diseases, those can alter the course of the disease and ultimately prevent it.

Penn Medicine associate vice president of health technology and academic computing Brian Wells even made the bold prediction that genetic sequencing may become less relevant as cancer treatments become increasingly sophisticated.

If we discover one immunotherapy that applies to all cancers, we really dont need to sequence your genome anymore, Wells said. Were at a tipping point and sequencing could become less important.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:With precision medicine, social determinants could be more insightful than genetics

More here:
Will patients' lifestyles become more important to precision medicine than gene sequencing? - Genetic Literacy Project

Behind the incredible process of developing targeted gene therapies to fight diseases like cancer lies an incredibly mundane problem that prevents these treatments from getting to patients paperwork and procedures.

While $5.7 billion was invested in companies developing cellular and genetic therapies, and with 800 clinical trials initiated worldwide and the first two CAR-T cell therapies expected to launch into market later this year, businesses still saythe ability to get these treatments to patients is limited by paperwork, supply chain management, and last mile delivery.

So GE (through its GE Ventures arm), the Mayo Clinic (through Mayo Clinic Ventures) and the venture investment firm DFJ have invested $13.75 million to back Vineti a software platform the companies are billing as a solution to gene therapys supply chain problem.

Its only the sixth company to have actually been built by GEs internal business team and spun out by the conglomerates venture arm.

According to company co-founder and former GE Ventures managing director Amy DuRoss, the process for developing and managing gene therapies is critical to the success of the treatment.

Amy DuRoss, chief executive at Vineti

To that end, Vinetis software tracks logistics, manufacturing and clinical data to improve treatments and drive down the cost of these therapies (which are mainly only accessible to those people with the very best health plans).

The startups technology was actually born out of necessity (always the mother of invention) and came from conversations that GE was having with a large, undisclosed customer.

A pharma company that is a regular client of GE Healthcare said we are solving late stage cancer and we want to take this commercial but we have not got the technology that can ensure that we can scale out these technologies in the commercial phase, DuRoss told me.

GEs healthcare business then took the problem to the companys venture investment and new business arm and began the development process of building a business.

In addition to DuRoss, who has been a luminary in the life sciences field since she helped with the push to get stem cell research approved in California; Vineti has a murderers row of leading healthcare talent.

Chief strategy officer Heidi Hagen, was the former SVP of Operations for cell immunotherapy pioneer Dendreon; chief technology officer Razmik Abnous was the chief technology officer at the healthcare data management juggernaut Documentum; and Malek Faham, the companys chief science officer, literally worked on some of the foundational science for gene therapies.

While the companys technology could have applications for a number of different treatments, and be used for several kinds of therapies, the focus, for now, is on cancer.

Cancer is a bullseye, says DuRoss. It is arguably the biggest cause of human suffering [and] there are treatments already in phase three, that if brought to market effectively could mark a turning point in medicines battle against the deadly disease, she said.

We see an opportunity as data accrues to the system over time for a use case in predicting therapy based on outcome data but were not making these claims today, said DuRoss.

Mayo Ventures had been working with GE for two years from the initial concept to the close of this new round of financing for Vineti. Its one of only 15 companies that the Clinic has backed since the formation of Mayo Clinic Ventures, and according to Andy Danielsen, the vice chair of Mayo Clinic Ventures.

One thing with Vineti that we liked is that we have a commitment to cell and gene therapies at Mayo, said Danielsen, so the interests were aligned. Vineti will make the gene and cell therapy production process more efficient and as a result, less costly. Its all part of the equation of making these therapies more affordable and opening them up to a greater number of people.

Therapy supply chain

External ordering pages

Product tracking

Therapy scheduling

Identity verification

More here:
GE and the Mayo Clinic back software to bring cancer-fighting gene therapies to market - TechCrunch

A local family physician is taking much of the guesswork out of patient treatment with the help of drug-gene testing that determines how a persons genes affect their bodys response to medications.

The testing is also known as pharmacogenetics, a combination of the words pharmacology (the study of the uses and effects of medications) and genomics (the study of genes and their functions).

Dr. Monnie Singleton of Singleton Health Center in Orangeburg has been using pharmacogenetics testing for nearly a year to determine safe and effective medications and doses that will be tailored to a persons genetic makeup.

Pharmacogenetics testing is a revolutionary means of checking to see how patients are metabolizing the medications that they are taking. So were looking specifically at how a medication is metabolized by an individual, Singleton said.

He said drugs dont work the same for everyone and while it can be difficult to predict who will benefit from a medication, who will not respond at all and who will experience adverse drug reactions, the testing helps him eliminate the trial-and-error associated with prescribing medications.

This technology eliminates the need for us to just keep guessing at what might be the right medicine in an individual patient. I think as we move forward, were going to be looking specifically to see if the genetics in patients DNA makeup will allow proper metabolism of that drug, he said.

Singleton added, If the drugs arent metabolized normally, what we see in many people is that either not enough or too much enzyme is produced. If not enough enzyme is produced to metabolize the amount of medication the patient is taking, the patients blood levels of that drug will increase to the point of becoming toxic and them getting side effects and other adverse drug reactions.

If a person is manufacturing or making too much of the enzyme, then the medicine doesnt stay in their system long enough to work and it is being metabolized too rapidly.

Enzyme is a substance produced by a living organism that acts as a catalyst to bring about a specific biochemical reaction.

A small blood or saliva sample can help determine whether a medication may be an effective treatment for patients.

Singleton said a sponge is used to swab a patients mouth. The specimen is then shipped off for testing to Lawrenceville, Georgia-based, Alpha Genomix Laboratories, a molecular diagnostics laboratory dedicated to providing personalized patient care. Lab pesonnel look for changes to one or more genes that can affect a patients response to certain medications.

Singleton said a printout of an individual patients lab results are then sent back to his office.

We are testing for 26 different enzymes, or metabolic pathways, with this technology, he said.

Itll give a printout of several different classes of drugs. Whether that patient is taking drugs in that other class or not, it will still give a report as to whether a patient would metabolize it normally or not. So if a different medication needed to be prescribed for a different condition in the future, we could look at that list and see exactly what would be the best medication to start with, Singleton said.

The physician said 60 percent of his patients are on Medicare or Medicaid, both of which pay 100 percent of the testing cost.

The private insurances are beginning to pay for it, but they are not paying for it 100 percent, Singleton said.

What I have seen and have better come to understand is that 40 percent of the time, the antidepressants that are used with that trial-and-error method are the wrong medication. Using this guided therapy, or looking at the results of pharmacogenetics testing, allows me to select an antidepressant that the patient metabolizes normally," he said.

I select that medication to begin with and as a result, people get better quicker," Singleton said. "Ive certainly seen that in the area of depression. I have also seen it in the area of arthritis, gastroesophageal reflux disease and even when prescribing the statins for elevated cholesterol."

Patients who have had adverse drug reactions in the past and those who are taking five or more medications are among those who are recommended for pharmacogenetics testing, he said, noting that family members of patients who may not have had a good response to a medication may also be provided recommendations to see if they may benefit from testing.

Singleton said the testing is worthwhile and needed because it costs the federal government in excess of $3.5 billion a year to treat adverse reactions to drugs.

Forty percent of these adverse reactions are estimated to be preventable," he said.

I would say the overwhelming majority of the patients that we have talked to about the technology have elected to have the test done," Singleton noted. "On average, were having to make some change in a medication that the patient has been taking 30 percent of the time."

See the original post:
Physician using pharmacogenetics to determine best medications for individual patients - The Times and Democrat