On August 28, 2023, Baird analyst Joel Beatty expressed his confidence in Immutep (NASDAQ:IMMP) by reiterating an “Outperform” rating and maintaining a price target of $7. This forecast indicates a significant growth potential for the stock, considering its current share price of $2.11. Notably, other stock analysts also share a positive outlook on Immutep, with an average 12-month stock price projection of $8.50, suggesting a potential increase of 349.74%. It is crucial to acknowledge that these forecasts and targets are based on the opinions of analysts and prevailing market trends, and the actual performance of the stock may deviate from these predictions.
A team of researchers at the University of Kentucky has found that a drug used to treat multiple sclerosis (MS) is potentially effective as a therapy for Alzheimer's disease.
Alzheimer's is a progressive and irreversible neurological disorder. It's estimated 6.2 million Americans aged 65 and older are living with the disease that affects cognitive function, memory and behavior.
"We stand at the threshold of a critical endeavor to develop new treatment strategies against Alzheimer's disease," said Erhard Bieberich, Ph.D., a professor in the Department of Physiology in the UK College of Medicine. "We've uncovered that a medication already on the market, ponesimod (brand name 'Ponvory'), can reduce one of the hallmarks of this disease: neuroinflammation."
The findings were published in the journal eBioMedicine, part of The Lancet Discovery Science series in August.
The team studied ponesimod, an oral medication that the U.S. Food and Drug Administration (FDA) has approved to treat relapsing forms of MS. The medication reduces inflammation in the brain by targeting a specific receptor in the immune system to help regulate the body's response and prevent it from attacking the central nervous system. This receptor is activated by a lipid termed sphingosine-1-phosphate, the function of which is studied by the Bieberich lab.
"We are the first to show that ponesimod is effective in a mouse model for Alzheimer's disease," said Bieberich. "Since this drug is already in clinical use for therapy of relapsing multiple sclerosis, it is immediately available to be used in Alzheimer's disease therapy as well."
UK researchers homed in on a specific type of cell found in the central nervous system called microglia. The cells have several functions in our bodies, including regulating inflammatory responses in the central nervous system—the brain and the spinal cord.
Dysfunctional microglia are connected to neurodegenerative diseases like Alzheimer's because those cells help clear out the buildup of abnormal protein deposits in the brain—a distinct characteristic of the disease. Those buildups disrupt the communication between the brain's nerve cells and eventually die off.
"The clearance of those proteins is an important target for Alzheimer's disease therapy," said Zhihui Zhu, Ph.D., first-author of the study and one of the scientists in Bieberich's lab. "In our study, we reprogrammed microglia into neuron-protective cells that clean up toxic proteins in the brain, reduce Alzheimer's neuroinflammatory pathology, and improve memory in the mouse model."
As part of the project, researchers studied mice with specific genetic strains that express the major features of Alzheimer's in their brains. They treated half of the mice with ponesimod and measured specific cell activity in the brain. The mice's spatial memory was also tested through a maze behavior test.
"That specific test is a measure of the spontaneous tendency of the mice to alternate their free choices to enter the two arms of the maze," said Zhu. "Our tests indicate ponesimod rescues attention and working memory in mice with advanced Alzheimer's pathology."
Scientists also worked with UK's Alzheimer's Disease Research Center within the Sanders-Brown Center on Aging to obtain human brain samples to study. The data collected from those tests were consistent and also indicated ponesimod can be used as a therapy for Alzheimer's.
"Neuroinflammation is a hallmark of Alzheimer's, one of the major causes for disease progression and a promising target for therapy," said Bieberich. "Our study shows strong experimental evidence that ponesimod may be a therapeutic drug, which not only reduces neuroinflammation but also enhances the clearance of neurotoxic proteins in the brain in middle and late-stage Alzheimer's."
More information: Zhihui Zhu et al, The S1P receptor 1 antagonist Ponesimod reduces TLR4-induced neuroinflammation and increases Aβ clearance in 5XFAD mice, eBioMedicine (2023). DOI: 10.1016/j.ebiom.2023.104713
Nursing homes will soon have to meet federal minimum staffing requirements, the U.S. Department of Health and Human Services (HHS) announced Friday.
"Establishing minimum staffing standards for nursing homes will improveresidentsafety," HHS SecretaryXavier Becerrasaid in an agencynews releaseannouncing the proposal.
"When facilities are understaffed, residents suffer. They might be unable to use the bathroom, shower, maintain hygiene, change clothes, get out of bed or have someone respond to their call for assistance," Becerra said. "Comprehensive staffing reforms can improve working conditions, leading to higher wages and better retention for this dedicated workforce."
The proposal would set the minimum staffing that is equivalent to 3 hours per resident per day. Just over a half hour of that time would be from a registered nurse. Facilities would be required to have an RN on staff 24 hours a day, every day.
It is "an important first step," said Chiquita Brooks-LaSure, who heads the U.S. Centers for Medicare and Medicaid Services, which oversees nursing homes.
Right now, average U.S. nursing home caregiver staffing is 3.6 hours per resident per day, with an RN working for more than a half hour of that time, according to the Associated Press.
Still, officials said most nursing homes would need to increase staffing.
"I would caution anyone who thinks that the status quo—in which there is no federal floor for nursing home staffing—is preferable to the standards we're proposing," Becerra aide Stacy Sanders told the AP. "This standard would raise staffing levels for more than 75% of nursing homes, bringing more nurse aides to the bedside and ensuring every nursing home has a registered nurse on site 24/7."
The United States has nearly 15,000 nursing homes that care for 1.2 million people.
A 2001 study funded by CMS had recommended a much higher threshold of 4.1 hours of nursing care per resident daily, the AP reported.
The announcement of these new, but lower than first sought, thresholds disappointed advocates, who have said the requirements only consider the point at which someone could experience harm not overall quality of life, the AP reported.
"This was not the time for an incremental step," Richard Mollot, who leads the Long Term Care Community Coalition, told the AP. "You really had a once-in-a-generation opportunity."
On the other side of the issue, the American Health Care Association had lobbied against staffing mandates, citing insufficient Medicaid subsidies, hiring and retention issues and home closures.
AHCA President and CEO Mark Parkinson pointed out that "nursing homes are facing the worst labor shortage in our sector's history, and seniors' access to care is under threat.
"This unfunded mandate, which will cost billions of dollars each year, will worsen this growing crisis. It requires nursing homes to hire tens of thousands of nurses that are simply not there," he said in an association news release.
In all, 38 states and the District of Columbia have their own staffing requirements, some quite low.
Residents and low-paid nurse's aides have long dealt with staffing issues, the AP reported.
Those shortages were exacerbated during the pandemic, when more than 167,000 U.S. nursing home residents died from the virus.
Yet staffing shrunk afterward, with 218,200 fewer employees now than in February 2020, according to the U.S. Bureau of Labor Statistics.
The proposed minimum staffing rule now enters a public comment period.
Despite advances in treatment for high cholesterol, heart disease remains the leading cause of death in the U.S. Scientists at the Medical College of Wisconsin (MCW) are investigating the role of a form of cholesterol called very-low-density lipoprotein—and their findings may lead to new treatment options in the future.
The research team is led by Ze Zheng, MBBS, Ph.D., MCW assistant professor of medicine (endocrinology and molecular medicine); co-leader of the MCW Cardiovascular Center's Atherosclerosis, Thrombosis and Vascular Biology Program; and associate investigator at Versiti Blood Research Institute. The team's findings were recently published inScience, where Dr. Zheng served as the paper's senior author.
François Poulletier de la Salle successfully isolated cholesterol for the first time from a gallstone in 1769 when his peers believed blood contained only a single protein and no fat. Scientists worked busily to define its molecular formula and shape, and better understand its connection to the accumulation of plaque in blood vessels and the development of heart disease. The first statin was approved by the Food and Drug Administration (FDA) in 1987 to treat patients with high cholesterol and reduce their risk of suffering heart attacks and strokes. In 2015, the FDA approved a new type of drug, known as proprotein convertase subtilisin-kexin type 9 inhibitors, to give cardiologists another tool for patients whose cholesterol levels are still too high after treatment with statins alone.
Yet, heart disease is still the leading cause of death in the U.S. according to the Centers for Disease Control and Prevention and stroke continues to be a major issue as the fifth leading cause of death. One clinical trial following patients taking proprotein convertase subtilisin-kexin type 9 inhibitors demonstrated a benefit, while also revealing an opportunity for improvement as the absolute risk reduction was considered modest at 1.5%.
"It is clear that there is more going on than just what statins and these newer inhibitor drugs can control," says Dr. Zheng. "More therapies are needed, and to get them we need to know more about other sources of risk for heart disease, especially heart attacks and strokes."
Several forms of cholesterol circulate in our bloodstream. The type commonly referred to as "bad cholesterol" is carried by a protein called apolipoprotein B (apoB) which forms well-structured particles with lipids and proteins. These particles serve as stable vehicles for transporting lipids such as cholesterol in the bloodstream. These lipid-rich particles mostly include very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL). The current drugs for lowering cholesterol reduce LDL levels. While substantial evidence shows that LDL is important to control, it is not the only risk factor for heart disease. In fact, the other lipoproteins in the same group as LDL are not reduced by much with available treatments. Dr. Zheng and team are investigating how to reduce levels of other members of this family of lipoproteins, especially VLDL.
"With my background in lipid metabolism, I found myself consistently checking lipid levels even during studies regarding blood clot lysis and how an impairment in the body's ability to remove blood clots affects the risk of blood vessel blockages," Dr. Zheng adds. "I was just naturally curious about it, and I noticed that a protein I was studying may have an effect on the amount of circulating cholesterol."
In prior research, Dr. Zheng has helped define a new cellular source of this protein, tissue-type plasminogen activator (tPA), and its role in breaking down blood clots and preventing blood vessel blockages. To understand its potential influence on cholesterol levels, her team used a gene-editing technique to stop liver cells from producing tPA in mice prone to blood vessel plaque formation. The scientists found that the mice developed increased lipoprotein-cholesterol in this experiment, and then validated the findings in follow-up studies using human liver cells and a type of rat liver cell known to produce VLDL in a way similar to human liver cells. With these and other experimental results published in Science in September 2023, Dr. Zheng and her team have demonstrated a new, important role that liver tPA influences blood cholesterol levels while underscoring a meaningful connection between the liver, heart, and blood vessels.
"After defining this new role for tPA, we turned our attention to the question of how it changes blood cholesterol levels," notes Wen Dai, MD, research scientist at the Versiti Blood Research Institute.
The liver contributes to the majority of the "bad" apoB-lipoproteins by making VLDL. The team focused on whether and how tPA impacts the process of VLDL assembly in the liver. Microsomal triglyceride transfer protein (MTP) is required for the assembly of VLDL due to its role carrying lipids to the apoB. The scientists determined that tPA binds with the apoB protein in the same place as MTP. The more tPA is present, the fewer opportunities MTP has to connect with apoB and catalyze the creation of new VLDL. If MTP is the quarterback trying to pass a cholesterol football to an open apoB receiver, then tPA is the cornerback breaking up the play.
"Based on our prior research, we knew it also was critical to look at tPA's primary inhibitor," Dr. Zheng says.
Plasminogen activator inhibitor-1 (PAI-1) is known to block the activity of tPA. Scientists also have found a correlation between PAI-1 levels in blood and the development of disease due to plaque formation and blockages in blood vessels. The team found that higher levels of PAI-1 reduced the ability of tPA to bind with apoB proteins, rendering tPA less effective at competing with MTP to prevent VLDL production. Returning to the biological gridiron, PAI-1 might be a decoy receiver that distracts tPA until MTP connects with apoB for a big gain. The team studied this interaction in human subjects with a naturally occurring mutation in the gene carrying the code for PAI-1. The researchers found that these individuals, as predicted, had higher tPA levels and lower LDL and VLDL levels than individuals from the same community who did not have the same mutation.
"We are investigating therapeutic strategies based on these findings regarding tPA, MTP and PAI-1," Dr. Zheng notes. "I think we may be able to reduce the residual cardiovascular risk that has persisted even as treatment has advanced."
More information: Wen Dai et al, Intracellular tPA–PAI-1 interaction determines VLDL assembly in hepatocytes, Science (2023). DOI: 10.1126/science.adh5207
A Chinese company developing a taxpayer-funded electric vehicle battery facility in Michigan published reports and video footage of its employees wearing what appears to be Red Army uniforms and pledging fealty to the Chinese Communist Party (CCP).
Gotion High-Tech — the Hefei, China-based parent company of Gotion Inc. — hosted multiple company trips in 2021 to CCP revolutionary memorials in Anhui Province, China, according to records first reported by the Daily Caller News Foundation.
During the trips, Gotion High-Tech workers wore Red Army outfits and pledged to “fight for communism to the end of my life.”
“I volunteer to join the CCP, uphold the Party’s platform, observe the provisions of the Party’s by-laws, carry out a member’s duties, carry out the Party’s decisions, strictly observe the Party’s discipline, be loyal to the Party, work hard, to fight for communism as long as I live, be ready at all times to sacrifice everything for the Party and people and never betray the Party,” the employees chanted during a trip to China’s Revolutionary Memorial Hall in July 2021, footage translated by the DCNF showed.
One month later, the company held a trip to Dabie Mountain to commemorate the CCP’s Long March, an historic march that led to the emergence of Chinese dictator Mao Zedong in early 1935.
The revelation that Gotion’s parent company hosted CCP trips for its employees and conducted party pledges comes as its Michigan project continues to face heightened scrutiny from locals, national security experts and Republican lawmakers.
Opponents of the project have noted the company’s allegiance to the Chinese government and often pointed to Gotion High-Tech’s corporate bylaws, which state that the company is required to “carry out Party activities in accordance with the Constitution of the Communist Party of China.”
The company’s 2022 ESG report states Gotion High-Tech “carried out thematic education activities such as the study of the 20th National Congress of the Communist Party of China, red theme education, and love for students,” The Midwesterner reported.
During Gotion company trips, Gotion High-Tech workers wore Red Army outfits and pledged to “fight for communism to the end of my life.”Gotion High-Tech
And earlier this year Gotion quietly registered as a Chinese foreign principal, according to FARA filings reviewed by Fox News Digital.
“Subnational incursions are afoot,” former U.S. Ambassador Joseph Cella, the co-founder of the Michigan-China Economic and Security Review Group, previously told Fox News Digital.
“China is on the hunt,” he continued. “The Chinese Communist Party is on the hunt. They are looking for these open doors to kick in, in states. And they have carried great sway. You just need to look at Gotion or CATL — textbook examples of this influence operation.”
During these retreats, Gotion High-Tech hosted themed events that aligned with communist ideas.LinkedIn
In April, Cella and fellow former U.S. Ambassador Peter Hoekstra, who helped found the Michigan-China Economic and Security Review Group, asked the Department of Justice to open a federal investigation into potential violations of the Foreign Agents Registration Act related to five-year hush agreements signed by state officials as part of the Gotion negotiations.
Democratic Michigan Gov. Gretchen Whitmer announced that Gotion would invest $2.4 billion to construct two 550,000 square-foot production plants along with other supporting facilities spanning 260 acres in northern Michigan. She applauded the proposal in her late 2022 announcement, saying it would shore up Michigan’s status as the “global hub of mobility and electrification.”
Then, earlier this year, the Michigan state Senate Appropriations Committee gave the final stamp of approval for granting Gotion $175 million in direct taxpayer funding to help build the facility.
In a 10-9 vote, some Democrats joined every Republican on the panel in voting against the funding, while only Democrats, including the committee’s chairwoman, voted in favor.
Michigan Gov. Gretchen Whitmer announced that Gotion is planning to invest $2.4 billion to construct production plants in Northern Michigan.AP
“I’m angry. I’m angry that this vote was slipped into the agenda today with as little information as possible so that people like me wouldn’t know it was happening,” Marjorie Steele, a local resident, said during the hearing. “I’m angry that you, our elected officials, have ignored my community’s pleas to table this vote until some small semblance of due diligence can be performed.”
“I can promise you that we will not stop at the local level,” she added. “We are tired of being abused, and we are not alone. This is not just a Mecosta County issue. Townships and counties across the state are uniting, sharing resources, manpower and grassroots activism. Your votes today, senators, are lines drawn in the sand.”
Gotion announced in August that it had scooped up 270 acres of land in Green Charter Township, Michigan, for the project.
Some of the purchased land is zoned for agriculture or residential use, while the majority is zoned for industrial use.
Neither Gotion nor Whitmer’s office responded to request for comment by time of publication.
The Biden administration will for the first time send controversial armor-piercing munitions containing depleted uranium to Ukraine, according to a document seen by Reuters and separately confirmed by two U.S. officials.
The rounds, which could help destroy Russian tanks, are part of a new military aid package for Ukraine set to be unveiled in the next week. The munitions can be fired from U.S. Abrams tanks that, according to a person familiar with the matter, are expected be delivered to Ukraine in the coming weeks.
One of the officials said that the coming aid package will be worth between $240 million and $375 million depending on what is included.
The value and contents of the package were still being finalized, the officials said. The White House did not immediately respond to a request for comment.
Although Britain sent depleted uranium munitions to Ukraine earlier this year, this would be the first U.S. shipment of the ammunition and will likely stir controversy. It follows an earlier decision by the Biden administration to provide cluster munitions to Ukraine, despite concerns over the dangers such weapons pose to civilians.
The use of depleted uranium munitions has been fiercely debated, with opponents like the International Coalition to Ban Uranium Weapons saying there are dangerous health risks from ingesting or inhaling depleted uranium dust, including cancers and birth defects.
A by-product of uranium enrichment, depleted uranium is used for ammunition because its extreme density gives rounds the ability to easily penetrate armor plating and self-ignite in a searing cloud of dust and metal.
While depleted uranium is radioactive, it is considerably less so than naturally occurring uranium, although particles can linger for a considerable time.
The United States used depleted uranium munitions in massive quantities in the 1990 and 2003 Gulf Wars and the NATO bombing of former Yugoslavia in 1999.
The U.N. nuclear watchdog, the International Atomic Energy Agency, says that studies in former Yugoslavia, Kuwait, Iraq and Lebanon "indicated that the existence of depleted uranium residues dispersed in the environment does not pose a radiological hazard to the population of the affected regions."
Still, the radioactive material could add to Ukraine's massive post-war clean-up challenge. Parts of the country are already strewn with unexploded ordnance from cluster bombs and other munitions and hundreds of thousands of anti-personnel mines.
The Wall Street Journal reported in mid-June the U.S. was considering sending depleted uranium rounds to Ukraine.
Recent weapons aid packages for Ukraine have included artillery, air defense missiles and ground vehicles as Ukraine's counteroffensive grinds on. Reuters was unable to determine what else the package contained besides the depleted uranium rounds.
Funding authorization for the aid package comes through the Presidential Drawdown Authority, which authorizes the president to transfer articles and services from U.S. stocks without congressional approval during an emergency. The material will come from U.S. excess inventory.
The security assistance for Ukraine since the full-scale Russian invasion in February 2022 has been more than $43 billion.
Group 2 data available to date support primary safety and feasibility endpoints of single-day bolus dosing of CT-0508
New translational analyses combining group 1 & group 2 continue to support CAR-M mechanism of action, demonstrating a correlation between biomarkers and best overall response
Carisma Therapeutics Inc. (Nasdaq: CARM) ("Carisma" or the "Company"), a clinical stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, will present findings today at the 8th Annual CAR-TCR Summit from its Phase 1 clinical trial of the Company's lead product candidate, CT-0508, a human epidermal growth factor receptor 2 ("HER2") targeted chimeric antigen receptor macrophage ("CAR-M") for the treatment of advanced/metastatic HER2 overexpressing cancers.
The presentation includes data from group 1 (n=9) and group 2 (n=5). Patients in both groups received the same total dose (up to 5x109 CT-0508) either via a fractionated, multi-day infusion regimen (group 1) or via a single-day bolus infusion (group 2). The data are drawn from the ongoing clinical trial led by Kim A. Reiss, MD, principal investigator of the Phase 1 clinical trial and an associate professor of Hematology-Oncology in the Perelman School of Medicine at theUniversity of Pennsylvania.
In the presentation, Michael Klichinsky, PharmD, PhD, Co-Founder and Chief Scientific Officer at Carisma, will present data demonstrating that, in both groups, CT-0508 was successfully manufactured for patients and that the administration of CT-0508 was well-tolerated after infusion with no dose-limiting toxicities reported to date.
"As the CT-0508 trial progresses, it is promising to see consistent results supporting the safety profile, feasibility, and mechanism of action of this first-in-class CAR-M investigational therapy," commented Dr. Klichinsky. "We look forward to results from the CT-0508 combination sub-study with pembrolizumab and continued development of CAR-M and CAR-Monocyte therapies."
Previously, Carisma presented findings from group 1 showing that CT-0508 remodeled and activated the tumor microenvironment ("TME") and initiated anti-tumor T cell immunity. Translational analyses combining group 1 and group 2 show that various biomarkers including metrics of TME activation, T cell activation, and HER2 status correlate with best overall response ("BOR") of stable disease, providing further evidence of the CT-0508 mechanism of action.
