Barrow Institute Gets Largest-Ever Grant To Seek Cure for Glioblastoma

Barrow Neurological Institute has initiated a $50 million effort, supported by the single largest research grant in the history of brain tumor research, to seek a cure for the deadliest form of brain cancer. Funding from The Ben and Catherine Ivy Foundation will be used to dramatically accelerate drug discovery and clinical testing for glioblastoma in the newly-formed Ivy Brain Tumor Center at the Barrow Neurological Institute.

The Ivy Center will become a cornerstone at Barrow, which conducts more brain tumor operations than any hospital in the nation, and is part of Dignity Health St. Joseph’s Hospital and Medical Center. Already screening malignant brain tumor patients from around the world, the new Center will ultimately mean that every patient, regardless of diagnosis or state of the tumor, will have the individualized option for an experimental therapy.

“This grant will fast track discovery and offer support and hope to those battling glioblastoma and other malignant brain tumors,” says Nader Sanai, MD, director of neurosurgical oncology. Dr. Sanai is an internationally renowned pioneer in glioblastoma research and will head the new Center. “The formation of the Ivy Brain Tumor Center will propel our singular research strategy to a new level of personalized medicine as we put a laser focus on discovering a cure,” he said. “The Ivy Foundation’s commitment is a true gift of hope.”

Catherine Ivy, president of The Ben and Catherine Ivy Foundation, said the Center’s ultimate goal is to cure brain cancer. “The more we discover, the more we can do to help patients and their families. Our Foundation has partnered with renowned medical and research programs throughout the United States and even internationally,” she said. “After years of assessment, we have decided to invest in the Ivy Brain Tumor Center at Barrow. We think Barrow and the new Ivy Brain Tumor Center are our best bet. ”

More than 138,000 Americans currently are living with a malignant brain tumor and more than nine out of 10 diagnosed with glioblastoma die within five years. Market forces and a string of high-profile clinical trial failures have led pharmaceutical firms to de-prioritize malignant brain tumor patients. Between 1998 and 2014, 78 investigational brain tumor drugs entered advanced clinical trial evaluation and 75 failed.

This lack of new drugs led Dr. Sanai in 2016 to launch a bold approach to treat glioblastoma with Barrow’s ‘Phase 0’ trials. In a Phase 0 trial, a patient receives a small dose of an experimental drug the day before surgery. During the operation, surgeons collect the patient’s samples and a team of scientists immediately test for the effectiveness of the drug. Results are available in days and, if the trial drug proves to be active, the patient goes on to receive aggressive treatment with higher doses. This approach is a unique form of personalized medicine and the first of its kind for brain tumor patients.

Prior to Barrow’s daring expansion into Phase 0 trialing, complex studies like this were only attempted at the National Institutes of Health. Now, Barrow is leading a national movement to rapidly identify new drugs that will save lives. “Phase 0 trials are the quickest route to identify individualized strategies for treating glioblastoma and our approach demands only a fraction of the time and costs associated with traditional drug research and development,” says Dr. Sanai. “With the Ivy Foundation’s grant and the Barrow’s expertise in Phase 0 trialing, we believe glioblastoma will meet its match.”

The Ben and Catherine Ivy Foundation, based in Scottsdale, Ariz., is the largest non-governmental funding mechanism of brain tumor research in the world, having committed more than $123 million to patient-focused research on gliomas, a type of tumor that occurs in the brain and spinal cord. Ivy became involved in brain tumor research when her husband, Ben, lost his battle with glioblastoma in 2005.

“Thanks to the Ivy Foundation’s inspiring commitment, the Barrow Neurological Institute has established the Ivy Brain Tumor Center, a 20,000 square foot state-of-the art facility that provides Dr. Sanai and his team of scientists and clinician specialists with state-of-the-art resources to focus on accelerated patient trials and save lives,” said Katie Cobb, President of the Barrow Neurological Foundation.

https://www.biospace.com/article/releases/barrow-receives-largest-grant-in-history-to-seek-cure-for-deadly-brain-cancer/

Gov Takeover of Medicine Began in 1942: J. of American Physicians & Surgeons

More Democrats are lining up behind “Medicare for All” as the midterm elections approach, but the idea under different names has been proposed repeatedly since 1942, as shown in the timeline outlined in the fall issue of the Journal of American Physicians and Surgeons by Jeremy Snavely.

“The last 75 years have seen exponential growth in government interference in American medicine. The result has been soaring costs and decreased quality and access,” he writes.

The Wagner-Murray-Dingell bill, providing for comprehensive health insurance under Social Security, was introduced in 1943.The Association of American Physicians and Surgeons (AAPS), now celebrating its 75^th anniversary, was founded to defeat this bill.

The incremental approach was adopted when Wagner-Murray-Dingell failed. As federal funding was provided for various programs, federal controls followed. Not long after Medicare was adopted in 1965, the federal government was dictating quality standards, criteria for medical necessity, the type of insurance that employers had to offer, Medicare price caps and controls, and methods of medical record-keeping, as Mr. Snavely details.

These measures generally worked to the disadvantage of independent practitioners. The Clinton Health Security Act, defeated in part thanks to AAPS v. Clinton, would have virtually outlawed private payment for medical services. Obama’s Affordable Care Act imposed mandates that outlawed affordable health insurance coverage for those not qualifying for premium subsidies. The Trump Administration is now increasing options outside of ACA-controlled plans, Mr. Snavely notes.

“Here’s one shocking fact that demonstrates magnitude of the [ACA] policy debacle,” he writes: “The federal government spent $341 billion from 2014 through 2016 to increase private coverage by just 1.7 million people…. That’s $200,000 per person.”

More controls continue to be imposed on Medicare, such as ICD-10 coding requirements and more data sharing, and penalties have been greatly increased.

“As we close this time-line, the old becomes new again,” Mr. Snavely concludes.

The Journal of American Physicians and Surgeons is published by the Association of American Physicians and Surgeons (AAPS), a national organization representing physicians in all specialties since 1943.

https://www.biospace.com/article/releases/march-toward-government-takeover-of-medicine-began-in-1942-according-to-the-journal-of-american-physicians-and-surgeons/

Germ-Zapping Robots Help Hunterdon Med Center Cut Superbug Infection 76%

As germs and bacteria become increasingly resistant to cleaning chemicals and antibiotics, Hunterdon Medical Center recently deployed Xenex LightStrike™ Germ-Zapping Robots™ that use pulsed xenon ultraviolet (UV) light to enhance traditional room cleaning procedures as a key part of the hospital’s infection prevention program. The hospital has seen a 76% reduction in Clostridium difficile (C.diff) infection rates since it began using the robots to disinfect rooms.

Hunterdon Medical Center implemented two Xenex LightStrike Germ-Zapping Robots as part of its ongoing efforts to reduce the risk of healthcare-associated infections (HAI) – infections that patients acquire while receiving treatment in a hospital. The infections are caused by microorganisms such as Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant enterococci (VRE) and C.diff. Invisible to the naked eye, some microorganisms can live on hospital bedrails, tray tables, wheel chairs and doorknobs for up to 5 months — posing a risk to patients and hospital employees. Now, when Hunterdon’s Environmental Services team member has finished cleaning a room, they bring in a LightStrike robot to quickly zap away pathogens that may have been left behind.

Hunterdon was already following infection prevention best practices recommended by the Centers for Disease Control and Prevention (CDC) and The Society for Healthcare Epidemiology of America (SHEA), but decided to invest in the Xenex robots after evaluating peer-reviewed studies that showed significant infection rate reduction results from other facilities using LightStrike robots for room disinfection. The hospital recently attained Magnet recognition for the third time, a testament to its continued dedication to high-quality practices.

Compared with the first half of 2017, Hunterdon Medical Center saw a 76% decrease in C.diffinfections after implementing the Germ-Zapping Robots in the second half of 2017. “It was a huge percent decrease in our number of cases,” said Lisa Rasimowicz, MSN, RN, CIC, director of infection prevention at Hunterdon. “The war against germs is getting tougher as they become resistant to cleaning chemicals. We want to utilize every weapon possible in our battle against infectious diseases to keep our patients and employees safe. I’m very pleased to report that the robots, in partnership with our EVS team, are doing an excellent job.”

https://www.biospace.com/article/releases/lightstrike-germ-zapping-robots-help-hunterdon-medical-center-reduce-superbug-infection-rates-by-76-percent-/

EpicGenetics, Massachusetts General to Launch Fibromyalgia Clinical Trial

Fibromyalgia is a condition marked by widespread pain and sensitivity to touch. For quite some time, many physicians and the general public viewed it as a made-up disorder of neurotic housewives, partly because it was only diagnosed via symptoms and because it affects far more women than men. For physicians who believed in the disorder, diagnosing it was largely a matter of eliminating other possibilities.

Around 2012, researchers made a connection between fibromyalgia and a type of white blood cell called peripheral blood mononuclear cells. These types of cells apparently do not produce normal quantities of protective proteins in fibromyalgia patients.

Since then, a clinical diagnostic blood test, the FM/a Test, which is performed by Los Angeles-based EpicGenetics, has been approved for use by the U.S. Food and Drug Administration (FDA). And now, EpicGenetics and Massachusetts General Hospital (MGH) are launching a Phase II clinical trial to test a tuberculosis vaccine, CBG, as a potential treatment for fibromyalgia.

Bruce Gillis, chief executive officer of EpicGenetics, took time to speak with BioSpace about fibromyalgia, the FM/a Test and the upcoming clinical trial.

Gillis says, “Fibromyalgia for decades and even presently has been wrongly considered as a bogus affliction of neurotic, hypochondriacal and hysterical women. When we published our results in 2012 we changed the paradigm. We proved that fibromyalgia was not a syndrome, which was how it was classified before. A syndrome is defined as a collection of symptoms or complaints, nothing more. We proved that fibromyalgia is an actual medical disease. It isn’t even a rheumatic or rheumatologic disease, it’s a disease of the body’s immune system.”

As a result of the research findings, Gillis and a team of researchers associated with EpicGenetics, developed the FDA-compliant blood test, the FM/a Test for fibromyalgia. It is available in most states in the U.S., as well as Canada, Europe, Turkey, Mexico, Central and South America, the Caribbean, Hong Kong, Australia and New Zealand. It is now covered by Medicare and most insurance plans. Gillis notes, “Our test has a sensitivity that approaches 99 percent—no test is 100 percent—and a specificity, which is essentially how many times you eliminate anything false, approaching 94 percent. So it’s an extremely, extremely accurate test.”

In the course of marketing the test, EpicGenetics often found patients saying, “Great, you diagnosed me, but now what? There’s no treatment.” This led EpicGenetics and Gillis and his team to expand their research, which includes work with The University of California, Los Angeles (UCLA) and University of Illinois College of Medicine Chicago to sequence the exomes of fibromyalgia patients.

It also led them to Denise Louise Faustman at Massachusetts General Hospital. Her research is in autoimmune diseases, and she had been doing work with a vaccine for tuberculosis called Bacillus Calmette-Guerin (BCG) and its effect on the immune system, particularly in type 1 diabetes. Her research showed that BCG stimulates a cytokine called TNF, which is beneficial in autoimmune diseases.

Gillis told BioSpace, “We met with her and planned a strategy to use BCG in fibromyalgia, and applied through her to the FDA to allow the staff to investigate BCG in fibromyalgia, and the FDA has since granted this opportunity. We’re very excited, because BCG has been around for over a century, has little to no adverse consequences, has fewer side effects than a flu shot, and how now been established as being highly beneficial for immunotherapy for diseases like type 1 diabetes and multiple sclerosis (MS).”

Because the vaccine is well known and considered safe, the clinical trial isn’t to get the vaccine approved overall, but to get it approved for the indication of fibromyalgia.

The structure of the clinical trial is to enroll 300 patients who test positive for fibromyalgia with the FM/a Test. They will be split into two groups, one receiving the vaccine, the other receiving a placebo.

“Currently,” Gillis says, “the only objective way to get fibromyalgia confirmed is by having the test. We’re in the process of contacting the people who had the test and seeing if they want to participate. We’re encouraging other people who want to potentially volunteer to also get the test, so we can do this. The expectation is that if the results are as good as we hope, potentially in as little as six months, we will have further opportunity to expand the treatment to many, many more people as we collect the data. We don’t expect significant side effects and we expect fairly rapid responses to the BCG by the people who participate in the trial who receive it.”

And they hope that if the patients receiving the vaccine respond as they expect, they will be able to offer the vaccine to those receiving the placebo.

EpicGenetics is funding the trial. They also plan, Gillis says, “once we have the FDA approval for the indication, that anyone who gets the test and tests positively and decides they want treatment, we will also cover the cost of the BCG for them as well.”

Gillis also points out that fibromyalgia has similar symptoms to other illnesses, specifically chronic fatigue syndrome. Potentially, he says, there may be “one out of every 11 people on the planet who may have one or the other illness. So the ability to identify with accuracy if they do and the ability now to potentially reverse it is there for the taking.”

https://www.biospace.com/article/-cp8r-epicgenetics-and-massachusetts-general-hospital-to-launch-fibromyalgia-clinical-trial/

EPA to ease rules on methane emissions for oil-and-gas companies

The Trump administration is about to propose its latest rollback of Obama-era climate rules, moving to ease requirements for oil-and-gas companies that were designed to limit leaks of the heat-trapping gas methane, administration officials said.

The Environmental Protection Agency is planning to release on Wednesday a proposal that would make it easier for oil-and-gas companies to comply with rules designed to limit the amount of methane released into the atmosphere.

The EPA proposal aims to ensure oil-and-gas companies have more time to assess and safely repair infrastructure often in remote locations, according to a draft summary of the proposal. The proposed changes, among other measures, would give drillers a year to do leak inspections instead of just six months, and 60 days to make repairs instead of 30, the document said.

Environmentalists are likely to oppose the plan, asserting the delayed inspections and repair schedules are likely to increase the amount of harmful gases released into the environment, and that the proposal opens the door to further rollbacks of climate regulations.

https://www.marketwatch.com/story/epa-to-ease-rules-on-methane-emissions-for-oil-and-gas-companies-2018-09-10?siteid=rss&rss=1

Start-up AliveCor detects dangerous blood condition from heart signals

• AliveCor, working with the Mayo Clinic, develops a new test that screens for elevated potassium levels without requiring any blood.
• Instead it uses AI technology that looks for signals in electrocardiograms.
• Apple is expected to launch an ECG on its Apple Watch come Wednesday.

AliveCor, a Silicon Valley start-up that develops technology to monitor people’s heart health, on Monday received “breakthrough device” designation from the U.S. Food and Drug Administration for developing a new way to detect high blood potassium levels without requiring any blood.

AliveCor worked with doctors at the Mayo Clinic, which is also an investor in the company, to develop a new technology that looks for a dangerous condition called hyperkalemia without requiring any blood from the patient. It instead looks for patterns in electrocardiograms (ECGs or EKGs), which are essentially recordings of the electrical signals of the heart.

“It was a pie-in-the-sky idea that we could use AI to see something like this in the ECG when no one else could,” said Vic Gundotra, CEO of AliveCor, who previously worked on AI-related technology as a senior vice president of engineering at Google. “It’s a big milestone for us.”

Hyperkalemia is often caused by problems with the kidneys, like chronic kidney disease, which is suffered by some 30 million Americans, as well as type 1 diabetes and a slew of other medical conditions. It can be life-threatening for these patients, with symptoms including trouble breathing and irregular heartbeats.

The FDA’s “breakthrough devices” program was designed to speed up approvals for technologies and devices in rare cases. Regulators will consider cases where the product offers “more effective treatment or diagnosis for life-threatening or irreversibly debilitating diseases, for which no approved or cleared treatment exists or that offer significant advantages over existing approved or cleared alternatives,” according to its website.

The start-up currently sells an attachment to a smartphone to measure the heart’s rhythm, as well as a band that fits on Apple Watch. These devices sell for $99 and up.

‘Helping people age in place’

Hyperkalemia is typically found through a blood test, which is problematic for patients who prefer to remain at home.

The Mayo Clinic’s chair of cardiovascular medicine, Paul Friedman, told CNBC that “millions of people” are at risk of increased potassium levels. He views the screening tool as important, as many patients might not realize that they have hyperkalemia outside of the hospital.

He described a collaboration that involved Mayo’s subject matter experts working with AliveCor’s technologists to analyze a huge volume of anonymized patient data. The hospital is “selective” in such partnerships with technology companies, he explained.

“You do not want to give Jeff Bezos a seven-year head start.”

Hear what else Buffett has to say

“The big picture here is helping people age in place and stay at home,” Friedman said.

AliveCor’s Gundotra estimates that the product will take about a year to reach the market, as the company is still required to submit results from a clinical trial.

The company previously worked with Mayo on a method to identify a syndrome called LongQTS, which causes dangerous fast irregular heartbeats in response to stress and exercise.

Gundotra said he hopes to eventually offer AliveCor’s devices through the patient’s health insurance for patients who can’t afford the price tag.

Staying one step ahead of Apple

AliveCor’s Apple Watch band gets FDA clearance  4:10 PM ET Thu, 30 Nov 2017 | 04:57

The news comes at a time when Apple is gearing up for its big event on Wednesday, where it is expected to announce updates to its smartwatch. Top analyst Ming-Chi Kuo, who has a strong track record of predicting Apple products, expects that Apple will unveil an electrocardiogram of its own.

That would turn its device into more of a medical device, not just an exercise tracker, and open up opportunities for the company to sell to an older, sicker demographic.

Gundotra said that if Apple takes such a step, it would be an “encouraging sign,” with the “world’s most valuable company saying that an ECG is important.”

But he still warns that Apple would need to work with federal regulators to help its users understand what the data means and whether they need to seek medical attention or not.

Either way, Gundotra said AliveCor’s news represents a high point of his career in Silicon Valley.

“I’ve helped lead teams or been part of teams like Google Maps, Search and YouTube,” he said. “But very rarely do you get to work on technology that an independent body validates as having the potential to save lives.”

https://www.cnbc.com/2018/09/10/alivecor-gets-fda-breakthrough-status-for-bloodless-hyperkalemia-test.html

Mutation key to glioblastoma’s ‘immortality,’ could point to drug targets

Glioblastoma, the brain cancer that took the life of Sen. John McCain, has proven especially difficult to target with drugs. Now researchers at the University of California, San Francisco, believe they’ve discovered how a common cancer mutation drives glioblastoma—a finding that could inspire new targets for drug treatments, they say.

The mutation, which occurs in a gene regulator called TERT and is the most common mutation in glioblastoma, gives cancer cells “immortality,” or the ability to divide and spread indefinitely. By studying cells from glioblastoma patients, the UCSF researchers discovered that a particular form of a protein called GABP drives TERT promoter mutations. They published their observations in the journal Cancer Cell.

It was a particular subunit of the protein called GABP-ß1L that seemed to activate the mutant promoters, the researchers discovered. That subunit is a potential drug target that’s now being further investigated by UCSF spinoff Telo Therapeutics, in partnership with GlaxoSmithKline, according to a press release.

TERT is important because it’s one of two genes that encode telomerase, an enzyme that gives stem cells the ability to divide indefinitely. Most normal cells have limited lifespans, but many human cancers have activated telomerase because of TERT mutations. Hence their ability to spread and become deadly.

Targeting telomerase with drugs has proven challenging because of off-target effects on normal blood stem cells. The UCSF team believed a safer route would be to go after TERT promoters instead.

“You can’t create a drug to target a promoter itself, but if we could identify how GABP was binding to the mutated promoter in these cancers, we might have a remarkably powerful new drug target,” said senior author Joseph Costello, Ph.D., a UCSF neuro-oncology researcher and co-founder of Telo, in the statement.

Costello’s team used different techniques, including CRISPR gene editing, to eliminate GABP-ß1L from glioblastoma cells. When they did that, the growth of the cells slowed dramatically, they reported. Then they tried implanting both edited and unedited cells into mice. The unedited cells grew aggressively, eventually proving fatal, while the edited cells grew slowly and were less lethal. Because they were not targeting TERT itself, they believe a drug that inhibits GABP-ß1L would be unlikely to interfere with normal cell processes.

The search for effective treatments for glioblastoma has left a long string of failures. Most recently, VBL Therapeutics announced disappointing clinical trial results earlier this year for its combo treatment designed to cut off the blood supply to tumors.

Still, there is plenty of investor interest in startups pursuing new ideas in glioblastoma. Istari Oncology, a Duke spinoff, has raised about $5 million to advance its immuno-oncology approach to glioblastoma, which involves an engineered form of poliovirus. And Quentis raised $48 million earlier this year to pursue therapies that modulate endoplasmic reticulum stress response pathways, which are associated with poor outcomes in many cancers, including glioblastoma.

Costello and his colleagues at UCSF are working in partnership with GSK to find small molecules to target GABP-ß1L. Although their priority is glioblastoma, they believe their approach could ultimately be applied to many tumor types, as more than 50 human cancers have been linked to mutations in TERT promoters.

https://www.fiercebiotech.com/research/newly-discovered-clue-to-glioblastoma-s-immortality-could-point-to-drug-targets