Halting ALS with a gene therapy approach

An abnormality in the SOD1 gene is linked to some inherited cases of amyotrophic lateral sclerosis (ALS). So could turning off the mutated gene halt the disease? An international research team led by the University of California San Diego School of Medicine showed the potential of that strategy in mice by using a gene therapy approach.

A one-time injection of a gene-silencing RNA delivered by an adeno-associated virus (AAV) vector into the spinal cord prevented the onset of ALS in presymptomatic mice, and it blocked disease progression in rodents that had already developed symptoms. The team reported the findings in the journal Nature Medicine.

The SOD1 gene codes for an enzyme called superoxide dismutase. Normally, the enzyme breaks down superoxide radicals that are produced during cell metabolism. But in ALS, SOD1 mutations can create misfolded SOD1 protein, as toxic oxygen molecules persist, leading to the death of motor neurons.

The UC San Diego-led team postulated that a short hairpin RNA (shRNA)—an artificial RNA molecule that can silence gene expression—could be utilized to block the dysfunctional SOD1 gene.

Other researchers had tried delivering shRNA-bearing vectors into the blood via intravenous injection. In mouse models of ALS, disease progression was indeed slowed, but the approach only extended survival by about three months. In a more recent study, scientists used intrathecal injection into the cerebrospinal fluid, but the animals lived only two months longer despite being treated immediately after birth.

For the current study, the UCSD researchers injected the shRNA-containing AAV therapy into the spinal subpial space at cervical and lumbar spine levels.

The team observed impressive results. Remarkably, SOD1-mutated mice treated before disease onset never developed disabilities related to motor neuron functions when followed to an average age of 462 days. That means they didn’t lose functions like grip strength or orientation reflexes. The control animals, by contrast, started showing symptoms at about 306 days and reached the end-stage of ALS about three months later.

Further analysis showed that the therapy suppressed the accumulation of misfolded SOD1 protein and almost completely preserved motor neuron cells.

In mice that had already entered the symptomatic stage, the injection also blocked disease progression and further motor neuron degeneration, the team reported.

“At present, this therapeutic approach provides the most potent therapy ever demonstrated in mouse models of mutated SOD1 gene-linked ALS,” the study’s senior author, Martin Marsala of UCSD, said in a statement.

Several other strategies have been developed aimed at decreasing the production of mutated SOD1 protein. Swiss biotech Neurimmune has a recombinant antibody called α-miSOD1, which the company developed based on memory B cells that are found in healthy elderly people and that protect against misfolded SOD1. In mouse models of ALS, the drug extended the animals lives by up to two months.

Antisense oligonucleotide therapy is another potential modality for fighting neurodegenerative disease. Biogen recently showed its antisense drug tofersen (BIIB067) was well tolerated in ALS patients in a small phase 1 study. At its highest dose, the drug cut SOD1 protein levels in spinal fluid and the patients performed well on certain clinical function tests.

Marsala and colleagues now plan to run additional studies of their spinal subpial shRNA approach in a large animal model to determine the optimal, safe dosage of the treatment.

“In addition, effective spinal cord delivery of AAV9 vector in adult animals suggests that the use of this new delivery method will likely be effective in treatment of other hereditary forms of ALS or other spinal neurodegenerative disorders that require spinal parenchymal delivery of therapeutic gene(s) or mutated-gene silencing machinery, such as in C9orf72 gene mutation-linked ALS or in some forms of lysosomal storage disease,” Marsala said in the statement.

https://www.fiercebiotech.com/research/halting-als-a-gene-therapy-approach

At CES, tech will show how it’s the key to value-based care

Twenty-five years ago, stem cell research was still in its infancy. Health records were only just going from paper to computer. Telehealth was nonexistent.

Today, people are living longer, doctors are conducting surgeries from across the world, and we can get diagnoses and order prescriptions online, without ever having to enter a doctor’s office.

Yet, for all these advancements, the health care industry remains stuck in an incentive structure that encourages – and even rewards – practitioners for over-testing or pushing unnecessary treatments. Technology is improving the accuracy and efficacy of treatment, but bureaucratic precedence often wins.

We need a better approach.

Value-based healthcare — in which health care providers are paid based on outcomes, not services rendered — may be the answer.

This “quality over quantity” model can make health care more effective and more affordable (a much-needed change, considering health care costs in the U.S. skyrocketed to $3.65 trillion last year). If done right, it can incentivize doctors to provide quality care and cut back on over-testing, and empower patients to take control of their wellness. And it can address physician and caregiver shortages and unburden health care by making it easier for the millions of Americans to age in their homes rather than be institutionalized.

As consumers and leaders in the public and private sectors look to the future of health care, we must keep in mind what’s on the technological horizon that will help bring this future to life. Advancements in digital health address some of the most pressing global issues of our generation, including opioid dependence, mental illness and chronic disease.

CES 2020 — the world’s largest, most influential technology event — will showcase hundreds of the newest technologies poised to disrupt the health care industry. Companies including Philips, Omron Healthcare, Myant, P&G, Cigna, Humana and Johnson & Johnson will present their newest products and cutting-edge research. And CES will partner with the American College of Cardiology Foundation to offer continuing medical education (CME) credits to doctors, nurses and other medical professionals to highlight tech innovations creating solutions for patient care.

Here are some of the technologies you’ll see at CES 2020 this January that can help make value-based care a reality:

Remote patient monitoring

Remote patient monitoring technology makes earlier diagnoses, better outcomes and cost savings available to more and more patients. According to a recent CTA survey, two in three physicians intend to use remote patient monitoring technology to manage their patients’ health in the future.

With remote patient monitoring, wearables such as CarePredict’s Tempo for seniors can provide customized care such as serving as a call button, tracking food, water, and medicine intake and noting a senior’s location. Another innovation designed to help seniors is Electronic Caregiver, providing remote monitoring to ensure safety and wellness – and give family members and loved one’s peace of mind. Other apps can remind diabetes patients to take their insulin or allow physicians to monitor glucose levels over time. And technology such as Omron’s blood pressure monitor can actively track heart health.

The need for increased accuracy and cost savings has driven the demand for remote monitoring from both physician and payer perspectives. Through sensor innovation and miniaturization, consumer-grade monitoring/diagnostic devices are becoming more accurate and easier to wear and use — and we’ll see smaller, less invasive and more sensitive devices this year. The cost savings of adopting these devices should easily make the requisite patient education processes worthwhile.

Digital therapeutics

Digital therapeutics are a new breed of digital health devices enabling patients with chronic disease to better adhere to treatment protocols and providing doctors with more data on the effectiveness of various treatments. Digital therapeutics can provide personalized care programs based on a patient’s needs and abilities to prevent and manage conditions and diseases — from asthma, diabetes and Alzheimer’s to hypertension, ADHD and mental health issues — and reduce reliance on certain pharmaceuticals or other therapies. One such device is a product from Carrot Inc. called Pivot, which is a smoking cessation program that uses an FDA-cleared mobile breath sensor, consumer-grade mobile app, behavioral science and personal coaching to help individuals quit smoking.

With digital therapeutics, patients can receive daily in-home physical exercises. They can track their fitness and food intake to prevent the onset of diabetes and control obesity. They can measure their blood sugar levels. And they can receive motor, speech or cognitive behavioral therapy at home, through web-based applications or digital dashboards. Other technologies can monitor sleep patterns and provide access to personalized suggestions to improve sleep. Ebb Therapeutics, for example, develops products that help patients with insomnia through temperature sensing and control.

Virtual reality

New virtual reality (VR) technologies allow doctors to better perform surgeries remotely, or train doctors on new skills with immersive training tools. Robotic surgeries, used in the right context, are increasingly more accurate and mean smaller incisions. And VR means doctors can show patients exactly how their surgeries will happen, using virtual reconstructions of their own bodies. Simulators from Samsung can help patients with pain management, and VR games help patients keep on track with their physical therapy.

Patients and doctors alike realize expensive testing and treatments with minimal (or no) results are not always worth the time, cost or pain. The future of health care is lower costs, more accessible care and better outcomes.

Value-based care will be an important step toward reducing chronic disease and improving overall wellness.

And at CES, we see the new tools and technologies poised to enhance the patient experience and transform the future of health care.

Gary Shapiro is president and CEO of the Consumer Technology Association (CTA), the U.S. trade association representing more than 2,000 consumer technology companies.

https://www.fiercehealthcare.com/tech/industry-voices-at-ces-tech-will-show-how-it-s-key-to-value-based-care

Texas judge: Hospital can remove baby from life support

A Texas judge on Thursday sided with a hospital that plans to remove an 11-month-old girl from life support after her mother disagreed with the decision by doctors who say the infant is in pain and that her condition will never improve.

Trinity Lewis had asked Judge Sandee Bryan Marion to issue an injunction in Tarrant County district court to ensure that Cook Children’s Medical Center doesn’t end her daughter Tinslee Lewis’ life-sustaining treatment. Texas Right to Life, an anti-abortion group that is advocating for Tinslee, said the girl’s mother will appeal the judge’s decision.

Doctors at the Fort Worth hospital had planned to remove Tinslee from life support Nov. 10 after invoking Texas’ “10-day rule,” which can be employed when a family disagrees with doctors who say life-sustaining treatment should be stopped. The law stipulates that if the hospital’s ethics committee agrees with doctors, treatment can be withdrawn after 10 days if a new provider can’t be found to take the patient.

In a statement issued by Texas Right to Life, which opposes the “10-day rule,” Lewis said she was “heartbroken” over the judge’s decision. “I feel frustrated because anyone in that courtroom would want more time just like I do if Tinslee were their baby,” she said.

The hospital said in a statement Thursday that in order to keep Tinslee alive, she’s on a constant stream of painkillers, sedatives and paralytics. She currently has severe sepsis, which isn’t uncommon when patients require deep sedation and chemical paralysis, it said.

“Even with the most extraordinary measures the medical team is taking, Tinslee continues to suffer,” the hospital said.

Efforts to find another facility to take her have been unsuccessful. The hospital said it has reached out to more than 20 facilities. Texas Right to Life and Protect TX Fragile Kids have also been trying to find a facility to take her.

Prior to Thursday’s ruling, both sides agreed that if Marion denied the injunction request, the hospital would wait at least seven days before taking Tinslee off life-support. In her decision, Marion said the seven-day period would give the girl’s mother time to file a notice of appeal and a motion for emergency relief with a state court of appeals.

Tinslee has been at Cook Children’s since her premature birth. The hospital said she has a rare heart defect and suffers from chronic lung disease and severe chronic high blood pressure. She hasn’t come off a ventilator since going into respiratory arrest in early July and requires full respiratory and cardiac support.

Lewis testified at a hearing last month that despite her daughter’s sedation, she has a sense of the girl’s likes and dislikes, describing her as “sassy.” She said Tinslee likes getting her nails done but doesn’t like having her hair brushed.

“I want to be the one to make the decision for her,” Lewis said about removing her daughter from life support.

At the hearing last month, Dr. Jay Duncan, one of Tinslee’s physicians, described the girl’s complex conditions and Cook Children’s efforts to treat her, which have included about seven surgeries. The cardiac intensive care doctor said that for the first five months of Tinslee’s life doctors had hope she might one day at least be able to go home.

But Duncan said there came a point when doctors determined they had run out of surgical and clinical options, and that treatment was no longer benefiting Tinslee. Duncan said last month that the girl would likely die within half a year, and noted the hospital has made “extraordinary” efforts to find another facility for her.

“She is in pain. Changing a diaper causes pain. Suctioning her breathing tube causes pain. Being on the ventilator causes pain,” he said.

Duncan said there had been “many, many” conversations with Tinslee’s family about her dire condition.

Tarrant County Juvenile Court Judge Alex Kim issued a temporary restraining order to stop the removal of life support on Nov. 10. But Kim was removed from the case after the hospital filed a motion questioning his impartiality and saying he had bypassed case-assignment rules to designate himself as the presiding judge.

After his removal, Judge Marion, who is chief justice of Texas’ Fourth Court of Appeals, was assigned to hear the request for an injunction in Tarrant County district court.

The case has become a rallying point for Republicans in Texas, with the attorney general stating his opposition to the “10-day rule” and GOP state Rep. Tan Parker saying it “doesn’t fit with Texas values.”

The 1999 law that shields from lawsuits doctors who follow the process of going through an ethics committee was crafted by a task force that included lawmakers, attorneys, doctors and anti-abortion groups. Supporters of the law passed when George W. Bush, a Republican, was governor include the Texas Alliance for Life, the Texas Catholic Conference of Bishops and the Texas Medical Association.

Supporters say the law provides a framework for doctors and hospitals to resolve differences and ensures that doctors can’t be forced to perform medical interventions that cause harm or suffering.

https://www.modernhealthcare.com/safety-quality/texas-judge-hospital-can-remove-baby-life-support

Two blockbuster cancer drugs see New Year price hikes

Drugmakers raised prices on more than 400 drugs in the early days of 2020, including two blockbuster cancer treatments that have been top-expenditure drugs in Medicare Part B, according to healthcare analysts and CMS data.

The CMS attributed an increase in Part B premiums and deductibles in 2020 to increased spending on physician-administered drugs. Part B premiums and deductibles both rose 7% compared with 2019 levels.

Two of the 10 physician-administered drugs that Medicare spent the most money on in 2018 have seen price increases this January, healthcare research firm 3 Axis Advisors found. While providers may not pay the sticker price for drugs in Part B, beneficiary cost-sharing is tied to list prices.

Merck instituted a price increase of 1.5% for Keytruda, the second-highest expenditure Medicare Part B drug in 2018. Bristol-Myers Squibb increased the price for Opdivo, a drug used to treat small cell lung cancer, by 1.5%. Opdivo was the third-highest Part B expenditure drug in 2018.

More price hikes could come later in the month as drugmakers delay customary price hikes to avoid scrutiny. Drugmakers can increase prices at any time.

GoodRx, a company that helps consumers find lower prices on medicines at pharmacies, noted that the average January 2020 drug price increase so far is 5%, compared with 5.2% in 2019 and 8% in 2018.

The Medicare Payment Advisory Commission reported in June that two-thirds of Medicare Part B drug spending growth between 2009 and 2016 was attributable to prices, including price hikes on existing drugs and the launch prices of new drugs.

Even though price increases seem to be moderating in recent years, research by a not-for-profit run by 3 Axis co-founders showed launch prices for new brand-name drugs have risen significantly since 2006, according to one of the co-founders, Antonio Ciaccia.

“Our research has shown that launch prices are what have been growing while the de-emphasizing of increases on pre-existing drugs has occurred,” Ciaccia said.

Top House and Senate lawmakers used the 2020 price hikes to push their colleagues to pass major drug-pricing legislation this year, including measures that could reduce spending on physician-administered drugs.

Senate Finance Chair Chuck Grassley (R-Iowa) tweeted on Thursday to promote a policy that would force drugmakers to pay back Medicare for price hikes that outpace inflation in Medicare Parts B and D. That policy was included in legislation he authored with Finance ranking member Ron Wyden (D-Ore.), but it has proved a nonstarter for some Senate Republicans who view the policy as a form of price controls.

A preliminary analysis by the Congressional Budget Office estimated that the Grassley-Wyden inflationary rebates in Medicare Part B would save the federal government $10.7 billion over a decade. A similar policy for retail prescription drugs has estimated savings of $57.5 billion, as retail drug spending makes up a much larger portion of overall Medicare spending.

House Speaker Nancy Pelosi (D-Calif.) also used the price hikes to call for passage of her drug price negotiation bill. House Democrats’ proposal includes an inflationary rebate policy similar to the Grassley-Wyden bill, though prices are indexed to 2016 prices instead of 2019 in the Senate legislation.

The Campaign for Sustainable Rx Pricing, which includes members such as the American Hospital Association, the Federation for American Hospitals, Kaiser Permanente and several insurers, called for legislative action to address drug prices in response to the 2020 price increases.

“With an election approaching, the clock is already ticking. Lawmakers, in both parties, will need to work diligently to deliver relief for American patients,” CSRxP executive director Lauren Aronson said.

An HHS spokesperson said the Trump administration “remains steadfastly focused on lowering drug prices even further and ending foreign free-riding.”

The administration has not yet proposed a demonstration that would tie payment for some Medicare Part B drugs to prices in foreign countries. The policy has been under review at the Office of Management and Budget since June 2019.

https://www.modernhealthcare.com/finance/two-blockbuster-cancer-drugs-see-new-year-price-hikes

Hospitals Exploring Short-Term Housing For Homeless Patients

Hospitals around the country are seeking to reduce their bed counts to cut costs, but the most economically vulnerable patients present a unique obstacle that is only just beginning to be addressed.

The American Hospital Association and a number of regional hospital systems have begun initiatives to build temporary housing for homeless patients or those experiencing housing instability, Fox News reports.

For hospitals with a mandate not to discharge patients straight to the street or deny care based on ability to pay, a basic apartment could be much cheaper to operate than a hospital bed.

As well-funded hospitals sink billions into new construction and renovation to keep costs low, hospitals that serve Medicare- and Medicaid-covered populations have been struggling to keep the lights on in recent years due to spiraling costs.

Some creative solutions have begun to emerge at the local level. The Denver Housing Authority is partnering with Denver Health to renovate a vacant building on the latter’s main campus into low-income senior housing, but the hospital is leasing back one of the floors to create 15 transitional units, Fox News reports. Patients that would otherwise remain in the hospital due to uncertainty over their next living situation would be placed in the units while permanent housing of some sort is lined up.

Denver Health expects the units to cost $10K per patient each year, compared to the $2,700 per day for a hospital bed, Fox News reports.

AHA is currently working in 10 markets across the U.S. as part of its Hospital Community Cooperative Program to address social issues like housing instability that negatively impact health outcomes, Fox News reports. The organization projects that social inequities, including housing, will cost the country’s healthcare system $126B this year.

Safety net hospitals in urban and low-income areas bear a greater portion of those costs than facilities in affluent communities, since Medicare and Medicaid pay much less for care than most private insurers.

On top of that, nearly 28 million non-elderly Americans have no health insurance, according to a Kaiser Family Foundation report released in December.

The University of Illinois Hospital & Health Sciences System has put hundreds of thousands of dollars into a pilot program called Better Health Through Housing that discharges homeless hospital patients in its Chicago-area facilities to a network of living units with “intensive case management,” Fox News reports. The program is set to expand this year to 75 patients from its starting number of 26.

https://www.bisnow.com/denver/news/healthcare/hospitals-short-term-housing-homeless-expensive-beds-102364

Philadelphia landlord says offering telehealth to tenants is a ‘no-brainer’

On top of in-unit laundry and central air, landlord and CEO of Philadelphia-based Shift Capital is now offering his tenants telehealth services, according to The Why.

“The concept of landlords providing wraparound services for tenants, in particular, low-income tenants, is a no-brainer,” Brian Murray, CEO of Shift Capital, told The Why.

Mr. Murray operates around 100 affordable housing units in the Philadelphia area. Those renters will now be able to enroll to receive telehealth service for $10 a month. Mr. Murray partnered with Washington D.C. startup Health+ to roll out the services.

For $10 a month, Mr. Murray says that the services could help renters meet their healthcare needs while also maintain their jobs.

“Ideally, this really helps the mother who has the minimum-wage hourly job, and allows her an opportunity to not have to take the day off from work to take [her kids] to the doctor,” Mr. Murray told The Why. “It doesn’t take dollars off her table, she doesn’t lose money off her paycheck. That could start a downward spiral.”

Health+ delivers its services through a combination of a discount prescription drug card from Clever RX and Teladoc Health.

However, landlords should be cautious when thinking about offering telehealth services, according to James Plumb, MD, co-director of the Philadelphia-based Jefferson Center for Urban Health, as some of the services could create unintended consequences if no primary care physicians are involved.

https://www.beckershospitalreview.com/telehealth/why-a-philadelphia-landlord-says-offering-telehealth-to-tenants-is-a-no-brainer.html

VA to double down on EHR modernization in 2020

Department of Veterans Affairs will go live on its new Cerner EHR system at five sites in March 2020, according to a Jan. 2 ConnectingVets report.

VA expects to deploy the $16 billion EHR in March at the Mann-Grandstaff VA Medical Center in Spokane, Wash., as well as the center’s four community clinics.

With the new system, U.S. service members will have a single health record that will follow them throughout their military career, according to the report.

The agency also plans to prioritize veteran suicide prevention, caregiver benefits and Agent Orange disability benefits in 2020.

https://www.beckershospitalreview.com/ehrs/va-to-double-down-on-ehr-modernization-in-2020.html