Blood marker could help ID risk of debilitating peripheral artery disease

 To track cardiovascular health, doctors measure blood pressure, cholesterol levels and blood sugar, among a number of other cardiovascular disease risk factors. Such measures can help predict whether a person is at risk of heart attack or stroke. But there is no blood test that can accurately assess the degree to which a person's arteries may be narrowing or at risk of blockage.

Now, researchers at Washington University School of Medicine in St. Louis have shown that high levels of a specific protein circulating in the blood accurately detect a severe type of peripheral artery disease that narrows the arteries in the legs and can raise the risk of heart attack and stroke. The protein, called circulating fatty acid synthase (cFAS), is an enzyme that manufactures saturated fatty acids. Until recently, fatty acid synthase was thought to be found only inside cells. The new study suggests that fatty acid synthase also circulates in the bloodstream and may have an important role in the plaque formation characteristic of cardiovascular disease.

The study appears online in the journal Scientific Reports.

About 12 million people in the U.S. have some form of peripheral artery disease, a narrowing of the arteries in the legs, and about 1 million of these patients develop a severe form called chronic limb-threatening ischemia. These patients often undergo vascular surgery to open up their peripheral arteries in an effort to improve blood flow to the legs. In severe cases, patients may need to have the diseased leg amputated.

"These patients are at risk of losing their legs, which is devastating to quality of life," said senior author Mohamed A. Zayed, MD, PhD, an associate professor of surgery and of radiology. "They lose their capacity to walk, and about half of them die within the next two years. We need to identify these patients sooner, so we can help treat them aggressively much earlier in the disease course. Our data suggest that levels of cFAS in the blood could be an accurate predictor for which patients are at high risk of the severe forms of this condition."

Zayed and his colleagues collected blood samples from 87 patients before they underwent vascular surgery to treat chronic limb-threatening ischemia. The researchers found that cFAS levels in the blood were independently associated with the disease. A diagnosis of Type 2 diabetes and smoking status also were strongly and independently correlated with chronic limb-threatening ischemia. When all three of these factors were considered together, they could predict the presence of the disease with 83% accuracy.

The researchers also found that cFAS levels in the blood were associated with the fatty acid synthase content of plaque sampled from the femoral artery, the main vessel supplying blood to the legs. In addition, the researchers found that cFAS circulates through the bloodstream while bound to LDL, the so-called "bad" LDL cholesterol, which raises an intriguing question.

"Oftentimes, I will see patients in my practice who have high LDL but are otherwise healthy individuals -- they don't have evidence of disease in their arteries," said Zayed, who is also a vascular surgeon at Barnes-Jewish Hospital. "We've scratched our heads at this. Do we put these patients on cholesterol-lowering medication? Are they still at high risk of cardiovascular disease? Our guidelines tell us to be aggressive in treating these patients. But my suspicion is the problem is not just LDL. Rather, the problem is enzymes that are attached to LDL that are conferring the cardiovascular disease that we see, particularly in the peripheral arteries, as well as the coronary arteries that deliver blood to the heart and the carotid arteries that deliver blood to the brain."

The researchers have found that LDL is more abundant than cFAS in the blood, so the key measure may not be LDL itself, but how much of the LDL is carrying cFAS along with it.

In past work, Zayed and his colleagues showed that blood cFAS levels also are elevated in patients with plaque buildup in the carotid arteries, which supply blood to the brain. That work also showed that the cFAS circulating in the blood originates from the liver. The evidence suggests that LDL serves as a delivery vehicle for cFAS that then contributes to the formation of plaque in key arteries throughout the body.

Zayed and his colleagues also are investigating cFAS as a possible target of new drug therapies that could slow plaque buildup and treat or prevent cardiovascular disease.

"There are drugs that inhibit fatty acid synthase, and we're working on evaluating new ones that are more targeted," Zayed said. "None of them are ready for clinical trials in people for this purpose yet, but we're using those drugs to test animal models of the disease to see if they actually decrease the buildup of plaque in the arteries. It would be wonderful to be able to practice precision vascular medicine -- to tailor therapy to high-risk patients to reduce their risk of developing severe complications of cardiovascular disease."

In the meantime, Zayed is working with Washington University's Office of Technology Management to develop a test kit for measuring cFAS in the blood so that high-risk patients may be identified earlier.

This work was supported by the National Institutes of Health (NIH), grant numbers NIH/NIDDK P30 DK020589, NIH/NIDDK R01 DK101392, NIH/NHLBI K08 HL132060, and NIH/NHLBI R01 HL153262; the Vascular Cures Foundation Wylie Scholar Award; the American Surgical Association Research Fellowship Award; the Society for Vascular Surgery Foundation Research Investigator Award; and the Washington University School of Medicine Diabetes Research Center.

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Story Source:

Materials provided by Washington University School of Medicine. Original written by Julia Evangelou Strait. Note: Content may be edited for style and length.

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Journal Reference:

1. Shirli Tay, Gayan S. De Silva, Connor M. Engel, Nikolai Harroun, Amanda S. Penrose, Kshitij A. Desai, Yan Yan, Clay F. Semenkovich, Mohamed A. Zayed. Prevalence of elevated serum fatty acid synthase in chronic limb-threatening ischemia. Scientific Reports, 2021; 11 (1) DOI: 10.1038/s41598-021-98479-7

https://www.sciencedaily.com/releases/2021/10/211001100426.htm

Low-cost, portable device could diagnose heart attacks in minutes

 Researchers from the University of Notre Dame and the University of Florida have developed a sensor that could diagnose a heart attack in less than 30 minutes, according to a study published in Lab on a Chip.

Currently, it takes health care professionals hours to diagnose a heart attack. Initial results from an echocardiogram can quickly show indications of heart disease, but to confirm a patient is having a heart attack, a blood sample and analysis is required. Those results can take up to eight hours.

"The current methods used to diagnose a heart attack are not only time intensive, but they also have to be applied within a certain window of time to get accurate results," said Pinar Zorlutuna, the Sheehan Family Collegiate Professor of Engineering at Notre Dame and lead author of the paper. "Because our sensor targets a combination of miRNA, it can quickly diagnose more than just heart attacks without the timeline limitation."

By targeting three distinct types of microRNA or miRNA, the newly developed sensor can distinguish between an acute heart attack and a reperfusion -- the restoration of blood flow, or reperfusion injury, and requires less blood than traditional diagnostic methods to do so. The ability to differentiate between someone with inadequate blood supply to an organ and someone with a reperfusion injury is an unmet, clinical need that this sensor addresses.

"The technology developed for this sensor showcases the advantage of using miRNA compared to protein-based biomarkers, the traditional diagnostic target," said Hsueh-Chia Chang, the Bayer Professor of Chemical and Biomolecular Engineering at Notre Dame and co-author of the paper. "Additionally, the portability and cost efficiency of this device demonstrates the potential for it to improve how heart attacks and related issues are diagnosed in clinical settings and in developing countries."

A patent application has been filed for the sensor and the researchers are working with Notre Dame's IDEA Center to potentially establish a startup company that would manufacture the device.

Bioengineers Chang and Zorlutuna are both affiliated with Notre Dame's Institute for Precision Health. Additional co-authors from Notre Dame are Stuart Ryan Blood, Cameron DeShetler, Bradley Ellis, Xiang Ren, George Ronan and Satyajyoti Senapati. Co-authors from the University of Florida are David Anderson, Eileen Handberg, Keith March and Carl Pepine. The study was funded by the National Institutes of Health National Heart, Lung, and Blood Institute.

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Story Source:

Materials provided by University of Notre Dame. Original written by Brandi Wampler. Note: Content may be edited for style and length.

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Journal Reference:

1. Xiang Ren, Bradley W. Ellis, George Ronan, Stuart Ryan Blood, Cameron DeShetler, Satyajyoti Senapati, Keith L. March, Eileen Handberg, David Anderson, Carl Pepine, Hsueh-Chia Chang, Pinar Zorlutuna. A multiplexed ion-exchange membrane-based miRNA (MIX·miR) detection platform for rapid diagnosis of myocardial infarction. Lab on a Chip, 2021; DOI: 10.1039/D1LC00685A

https://www.sciencedaily.com/releases/2021/10/211001130251.htm

Medicago, Glaxo To Launch Trials Of COVID-19 Vaccine Candidate In Japan

 MEDICAGO TO LAUNCH CLINICAL TRIALS FOR COVID-19 VACCINE CANDIDATE WITH GSK'S PANDEMIC ADJUVANT IN JAPAN

* MEDICAGO’S COVID-19 VACCINE CANDIDATE HAS NOW COMPLETED ENROLLMENT OF ITS PHASE 2/3 CLINICAL TRIALS

* STUDY, WITH FINAL DATA FROM GLOBAL PHASE 2/3 STUDY OF VACCINE CANDIDATE, TO BE USED TO SUPPORT APPLICATION FOR APPROVAL IN JAPAN BY MARCH OF 2022.

https://www.marketscreener.com/quote/stock/GLAXOSMITHKLINE-PLC-9590199/news/GlaxoSmithKline-Medicago-GSK-To-Launch-Trials-Of-COVID-19-Vaccine-Candidate-In-Japan-36571209/

Omeros: FDA Found Deficiencies in Review of Biologics License Application

 Omeros Corp. said the U.S. Food and Drug Administration identified deficiencies that preclude discussion of labeling and post-marketing requirements/commitments for narsoplimab in hematopoietic stem cell transplant-associated thrombotic microangat this time.

Omeros said it was notified by the administration as part of FDA's ongoing review of the company's biologics license application for narsoplimab. The FDA stated the notification doesn't reflect a final decision on the information under review, Omeros said.

The FDA didn't provide specific details of the deficiencies in its notification. In a meeting held Sept. 30, the FDA expressed its intention to work with Omeros to resolve any issues as expeditiously as possible, Omeros said. However, the company said it doesn't currently expect any such resolution by the Oct. 17 target action date under the Prescription Drug User Fee Act.

Omeros said it is evaluating potential next steps as it awaits additional information. The company said it plans to obtain FDA approval for narsoplimab in HSCT-TMA, a frequently lethal complication of HSCT for which there is no FDA-approved treatment, as quickly as possible.

https://www.marketscreener.com/quote/stock/OMEROS-CORPORATION-5628248/news/Omeros-FDA-Found-Deficiencies-in-Review-of-Biologics-License-Application-for-Narsoplimab-36572090/

People Are Getting Moderna 'Boosters' Anyway

 Several sources have told MedPage Today that they've received a "booster" shot of Moderna, even though the vaccine isn't yet authorized for this indication.

These are people who don't fit the specific criteria for being immunocompromised that would qualify them for a third dose of the vaccine. Some of them are over 65 but didn't get their primary series with Pfizer. The majority got their shots at a pharmacy, not in a doctor's office.

"We both have two Moderna shots and a Moderna booster, figuring that even if the booster isn't approved yet, it can't hurt," said one source who is over 65 but not immunocompromised, speaking of himself and his wife. "Our family doc told us to get one ASAP."

While sources didn't share exactly how they got their Moderna "boosters," the immunocompromised are only required to self-attest to their condition, and don't need to bring a doctor's note to their pharmacies in order to get third doses, according to the CDC.

People have long been pursuing boosters or third shots of COVID vaccines, even before the FDA authorized a third dose of either vaccine for the immunocompromised in August, or Pfizer boosters for certain groups earlier this month.

In early August, for instance, ABC News reported on a leaked CDC memo that found about 1.1 million people had already received an unauthorized third dose of either vaccine -- and acknowledged that number was likely an undercount.

It's possible that number included a large proportion of immunocompromised patients seeking a third dose, but others may have simply been concerned about waning immunity in the face of the Delta variant.

One caution about forging ahead with a Moderna booster is that when the company submitted data to FDA for review, it focused on a 50-mcg shot, rather than the 100-mcg doses given for the first and second shots. It's not clear if the lower dose would carry fewer side effects, as the second Moderna shot garnered a reputation for packing a punch.

In addition to the possible differences in dose with any Moderna booster that's authorized in the future, there are also some differences with the third dose for the immunocompromised. That third shot is authorized at the 100-mcg dose at least 28 days after the initial two-dose series. Any Moderna booster would likely come 6 months after the primary two-dose series.

MedPage Today reached out to CVS and Walgreens to clarify their policies on Moderna boosters and third doses.

A Walgreens spokesperson said it's offering Pfizer boosters to eligible individuals, but Moderna "is not currently available as a booster, and we will continue to follow additional guidance from the FDA and CDC." The spokesperson also acknowledged providing third doses of either mRNA vaccine to immunocompromised individuals.

A CVS spokesperson said the company began administering Pfizer boosters last week, and that "more data on the effectiveness and safety of Moderna and Johnson & Johnson (Janssen) booster shots are expected in the coming weeks."

The CVS spokesperson also noted the availability of Pfizer and Moderna third shots for the immunocompromised, highlighting CDC guidance that "if the mRNA vaccine product given for the first two doses is not available or is unknown, either mRNA COVID-19 vaccine product (Moderna or Pfizer) may be administered."

The back-and-forth on boosters has led to confusion about eligibility. At this point, third doses of both mRNA vaccines are authorized 28 days after the primary series for those with very specific immunocompromising conditions as outlined by CDC's Advisory Committee on Immunization Practices (including solid-organ transplant recipients, those undergoing cancer treatment, and those on immune-suppressing drugs such as alkylating agents, antimetabolites, and tumor necrosis factor blockers). People with chronic conditions like heart disease or diabetes are not considered to be a part of this group.

Those who received a primary two-dose series with Pfizer are eligible for a booster shot (at the same dose as the original shots) at least 6 months after their second dose if they're 65 and older; if they're 18 to 64 and at high risk of having severe COVID; or if they're 18 to 64 and at high risk of contracting COVID-19 due to occupational exposure.

Given the confusion and "booster envy," President Biden has attempted to reassure Americans who are playing by the rules that they'll be okay.

"If you don't qualify for the booster, or you got the Moderna and Johnson & Johnson vaccines: if you're fully vaccinated, you're highly protected from severe illness even if you get COVID-19," Biden tweeted earlier this week.

https://www.medpagetoday.com/special-reports/exclusives/94789

FDA won't extend shelf life of J&J Covid vax, may extend life of Moderna shots

 The government will not extend the shelf life of hundreds of thousands of unused Johnson & Johnson Covid vaccine doses, but may soon extend the life of millions of Moderna vaccine doses, according to an internal email obtained by NBC News.

In an email sent to state health officials and health-care providers Friday morning, the Centers for Disease Control said the Food and Drug Administration will not further extend the life of Johnson & Johnson vaccines sitting on states' shelves across the country, leading to the potential waste of hundreds of thousands of doses.

The CDC told officials and health-care providers to check their Covid vaccine inventories for "many lots" of expiring Johnson & Johnson vaccine doses and told them that despite previous shelf-life extensions for Johnson & Johnson doses, the FDA will not take further action.

The email says, "There will be no more extension."

In the same message, the CDC notified states that the FDA will likely extend the expiration date of millions of doses of Moderna vaccine. Two sources who did not want to be identified told NBC News that an extension for Moderna would likely add up to two months to the life of vaccine doses.

The FDA referred inquiries to the companies and declined comment on the email. Moderna declined to comment. Johnson & Johnson did not immediately respond to a request for comment.

On July 28, the FDA extended the shelf life of the J&J doses to six months from manufacture. Doses have been rolling out to states in batches since the vaccine was approved in late February. Unused doses sent to states in April or earlier should expire soon.

It's unclear how many J&J doses could be wasted but the federal government has shipped 22 million doses to states and only 15 million have been administered so far, according to data from the CDC's website.

West Virginia Covid czar Dr. Clay Marsh said the state had recently disposed of 9,000 J&J doses. Virginia health officials told NBC News they had 26,936 J&J doses on the shelves, and Washington state had 57,883 doses as of Sept. 27. Arkansas has 11,284, Rhode Island has 6,825 as of this morning according to state officials.

Most states stopped ordering new J&J shots a few months ago and demand for the shot has not been strong, according to state health officials.

It's possible that doses on the shelves could be used as booster shots but only if the company files for authorization quickly and the FDA takes action by providing emergency use authorization for a J&J booster.

As of Sept. 21, Johnson & Johnson said it had provided all available booster data to the FDA but a formal filing has still not happened. In order for the booster approval to happen, the company would have to file, FDA officials would have to review the data and the CDC advisory committee would need to meet to weigh in.

Late Friday afternoon, the FDA announced an agency advisory committee would meet in mid-October to discuss boosters for both the J&J and Moderna vaccines.

https://www.nbcnews.com/health/health-news/fda-won-t-extend-shelf-life-j-j-covid-vaccine-n1280579

CTI BioPharma Misses Topline Endpoint with Covid-19 Treatment

  PRE-VENT amended to a Phase 2 study due to shifting COVID-19 treatment landscape -

- PRE-VENT did not achieve pre-defined statistical significance for the primary endpoint of proportion of patients who progressed to invasive mechanical ventilation and/or extracorporeal membrane oxygenation or died -

CTI BioPharma Corp. (Nasdaq: CTIC) today announced topline results from the PRE-VENT trial (NCT04404361) of pacritinib in hospitalized patients with severe COVID-19. PRE-VENT, a randomized, double-blind, placebo-controlled multicenter study, compared pacritinib/standard of care versus placebo/standard of care in hospitalized patients with severe COVID-19, including patients with and without cancer. The primary endpoint of the trial was the proportion of patients who progressed to invasive mechanical ventilation and/or extracorporeal membrane oxygenation or died by Day 28. The study was recently amended to a Phase 2 design due to the availability of COVID-19 vaccines and an evolving COVID-19 environment.

The final PRE-VENT analysis was conducted following the randomization of 200 patients. In patients with severe COVID-19 treated with pacritinib/standard of care, compared to placebo/standard of care, a statistically significant improvement in the primary endpoint of progression to invasive mechanical ventilation and/or extracorporeal membrane oxygenation or death by Day 28 was not demonstrated (26.3% vs. 24.8% [OR: 1.01 (95% CI: 0.51-1.99)], P=0.98).

Pacritinib was generally well-tolerated by patients with severe COVID-19, with lower rates of grade 3+ events and serious adverse events being reported in patients treated with pacritinib/standard of care compared to placebo/standard of care (29.2% vs. 40.6% and 20.8% vs. 32.7%, respectively). The most common adverse events comparing pacritinib/standard of care to placebo/standard of care were increased alanine aminotransferase (15.6% vs. 16.8%), anemia (12.5% vs. 17.8%), bradycardia (15.6% vs. 10.9%), constipation (12.5% vs. 12.9%), hypokalemia (12.5% vs. 12.9%), and hyperkalemia (9.4% vs. 10.9%).

https://finance.yahoo.com/news/cti-biopharma-announces-topline-data-200500807.html