Biden-Harris Released 99 Illegal Aliens On FBI Terror Watchlist Into US Communities

 A new interim staff report from the House Judiciary Committee and Subcommittee on Immigration Integrity, Security, and Enforcement, published on Monday, highlights how the Biden administration, with 'Border Czar' VP Kamala Harris, facilitated the greatest illegal alien invasion ever on the United States.

The report titled "Terror At Our Door: How The Biden-Harris Administration's Open-Borders Policies Undermine National Security And Endanger Americans" revealed that the failed southern border policies of President Joe Biden and VP Kamala Harris have flooded the nation with more than 5.4 million illegal aliens. Additionally, at least 1.9 million known "gotaways" also entered, bringing the total to 7.3 million illegal entries.

Fox News' Bill Melugin, who also reviewed the report, said the border data that dates back between 2021-23 shows "at least 99 illegal aliens on the FBI terror watchlist were released into the US after being arrested by Border Patrol at the southern border, and another 34 watchlisted aliens are still in DHS custody." 

And this. 

"With the border in chaos under the Biden-Harris Administration, the terrorist threat to the homeland has skyrocketed. This border insecurity has been the Administration's choice, and it is a mistake," the report stated. 

The report noted that 375 illegal aliens on the US Gov'ts terrorist watchlist have been apprehended by Border Patrol agents under Biden's first term with VP Harris as Border Czar. 

The report continued, "That is a more than 3,000 percent increase of watchlisted alien encounters compared to all four years of the Trump Administration." 

At the end of last month, leftist MSM spent days in an all-out propaganda media blitz to convince voters that VP Harris was never border Czar - that's because the nation killing open southern borders pushed by Biden & Harris is such a disastrous topic during the election cycle.

Meanwhile, national security 'experts' have warned countless times that the Biden-Harris Administration's open-border policies can only suggest it's only a matter of time before a terror event unfolds in the US.  

Just last week, we reported...

• Three Palestinian Terror Suspects Detained At Southern Border As Agents Lament Lack Of Resources

In June.

• 8 Suspected Illegal Alien Terrorists Arrested In New York, Philadelphia & LA

In April.

• Afghan Migrant On Terror List Released By Immigration Judge, Free To Roam USA

And in March.

• Iranian Assassin On The Loose In America, Targeting Trump-era Officials

This aged well. 

A majority of Americans care about two things ahead of the elections: 1) inflation and 2) the border. 

For Harris and Obama's Democrat party, there's no escaping that disastrous border issue.

https://www.zerohedge.com/markets/biden-harris-release-99-illegal-aliens-fbi-terror-watchlist-american-communities

Heart failure in type 2 diabetes: Current diagnostics unreliable in women

 A MedUni Vienna study has investigated gender-specific differences in the diagnosis of systolic heart failure in patients with type 2 diabetes. The results, recently published in the journal Cardiovascular Diabetology, show that the current methods are less reliable in women than in men.

In view of the prevalence of heart disease, particularly in women with type 2 diabetes, it is recommended that gender aspects be taken into account in existing guidelines in order to ensure the best possible care for patients.

As part of the study, the scientific team led by gender medicine specialist Alexandra Kautzky-Willer from the Division of Endocrinology and Metabolism (Department of Medicine III), in collaboration with Martin Hülsmann and other colleagues from the Division of Cardiology (Department of Medicine II), analyzed data from 2,083 patients with type 2 diabetes (T2D) collected over a period of five years. Common methods and parameters for the diagnosis of systolic heart failure in T2D were analyzed, with a particular focus on gender-specific differences.

T2D patients are up to four times more likely to have heart failure than people without T2D, with women more than twice as likely to be affected as men. Despite the pathophysiological differences between men and women, which lead to different predispositions and courses of the disease, there are currently no gender-specific recommendations for the diagnosis of heart failure in patients with T2D.

If symptoms are noted, the current guidelines recommend further investigations for both sexes, such as determining the marker NT-proBNP in the blood and performing an echocardiogram (cardiac ultrasound). According to the NYHA classification, a categorization is made according to the severity of the symptoms, from which treatment strategies are derived.

Early diagnosis is crucial for prognosis

As the current study shows, this standardized approach does not meet the specific needs of female and male T2D patients. While higher NYHA grades (reduced exercise capacity) are associated with higher NT-proBNP values, more frequent heart failure diagnoses and a higher risk of death in men, this correlation was not found in women.

In contrast, the significance of NT-proBNP for heart failure was significantly higher in both sexes, but especially in women, than the clinical symptoms. Apparently, women often have no symptoms for a long time or do not report them, even though they already suffer from manifest heart failure.

"Our results suggest that reduced performance may not be suitable for screening heart failure in women with T2D," concludes first author Sarah Hofer-Zeni (Clinical Department of Endocrinology and Metabolism).

"NT-proBNP values, on the other hand, can be very sensitive and early markers of heart failure, especially in women. Diagnosing the heart disease as early as possible and adapting the treatment with new, very effective drugs is essential for the prognosis of patients with T2D," adds study leader Alexandra Kautzky-Willer.

According to the research team, the results of the analyses also support the need for heart failure screening in women with T2D that is based less on symptoms and more on biomarkers, and for gender-specific aspects to be taken into account in the guidelines.

More information: Sarah Hofer-Zeni et al, Sex differences in the diagnostic algorithm of screening for heart failure by symptoms and NT-proBNP in patients with type 2 diabetes, Cardiovascular Diabetology (2024). DOI: 10.1186/s12933-024-02360-6

https://medicalxpress.com/news/2024-08-heart-failure-diabetes-current-diagnostic.html

New drug could turn back the clock on MS

 Multiple sclerosis (MS) degrades the protective insulation around nerve cells, leaving their axons, which carry electrical impulses, exposed like bare wires. This can cause devastating problems with movement, balance and vision; and without treatment, it can lead to paralysis, loss of independence and a shortened lifespan.

Now, scientists at UC San Francisco and Contineum Therapeutics have developed a drug that spurs the body to replace the lost insulation, which is called myelin. If it works in people, it could be a way to reverse the damage caused by the disease.

The new therapy, called PIPE-307, targets an elusive receptor on certain cells in the brain that prompts them to mature into myelin-producing oligodendrocytes. Once the receptor is blocked, the oligodendrocytes spring into action, wrapping themselves around the axons to form a new myelin sheath.

It was crucial to prove that the receptor, known as M1R, was present on the cells that can repair damaged fibers. Contineum scientist and first author Michael Poon, Ph.D., figured this out using a toxin found in green mamba snake venom.

The work, which appears Aug. 2 in Proceedings of the National Academy of Sciences, caps a decade of work by UCSF scientists Jonah Chan, Ph.D., and Ari Green, MD. Chan led the team to discover in 2014 that an obscure antihistamine known as clemastine could induce remyelination, which no one knew was possible.

"Ten years ago, we discovered one way that the body can regenerate its myelin in response to the right molecular signal, winding back the consequences of MS," said Chan, a Debbie and Andy Rachleff Distinguished Professor of Neurology at UCSF and senior author of the paper. "By carefully studying the biology of remyelination, we've developed a precise therapy to activate it—the first of a new class of MS therapies."

A dirty drug creates a clean opening

The original breakthrough came when Chan invented a method to screen drugs for their ability to instigate remyelination. The screen identified a group of drugs, including clemastine, that had one thing in common: They blocked muscarinic receptors.

Clemastine's benefits begin with its effect on oligodendrocyte precursor cells (OPCs). These cells stay dormant in the brain and spinal cord until they sense injured tissue. Then they move in and give rise to oligodendrocytes, which produce myelin.

For some reason, during MS, OPCs gather around decaying myelin but fail to rebuild it. Chan figured out that clemastine activated OPCs by blocking muscarinic receptors, enabling the OPCs to mature into myelin-producing oligodendrocytes.

Nerves and their myelin are notoriously hard to repair, whether due to MS, dementia or other injury. Green and Chan carried out a trial of clemastine in patients with MS, and it was a success—the first time that a drug showed the capacity to restore the myelin lost in MS. Despite being safe to use, however, clemastine was only modestly effective.

"Clemastine is not a targeted drug, affecting several different pathways in the body," said Green, Chief of the Division of Neuroimmunology and Glial Biology in the UCSF Department of Neurology and co-author of the paper. "But from the get-go, we saw that its pharmacology with muscarinic receptors could point us toward the next generation of restorative therapies in MS."

A snake venom toxin illuminates the right target

The researchers continued using clemastine to understand the curative potential of regenerating myelin in MS. They developed a series of tools to monitor remyelination, both in animal models of MS and in MS patients, showing that the benefits seen with clemastine came from remyelination—and pointing the way for how new drugs should be tested and evaluated.

They also found that clemastine's benefits came from blocking just one of the five muscarinic receptors, M1R, but the effect on M1R was middling, and the drug also affected the other receptors. The ideal drug would need to zero in on M1R.

At this point, the UCSF scientists needed an industry partner to advance the project. Ultimately, Contineum Therapeutics (then known as Pipeline Therapeutics) was formed to take a meticulous approach to creating that ideal drug. Chan and Green helped the company confirm that M1R was the right target for a remyelinating drug, and then make a drug that blocked it exclusively.

Poon, a biologist at Contineum, realized that MT7, a toxin found in the venom of the deadly green mamba snake, could reveal exactly where M1R was in the brain.

"We needed to prove, beyond doubt, that M1R was present in OPCs that were near the damage caused by MS," Poon said. "MT7, which is exquisitely selective for M1R, fit the bill."

Poon used MT7 to engineer a molecular label for M1R that revealed rings of OPCs gathering around damage in a mouse model of MS and in human MS tissue.

Developing a clinic-ready drug

A team of medicinal chemists at Contineum, led by Austin Chen, Ph.D., then got to work on the drug that Chan and Green envisioned, designing PIPE-307 to potently block M1R and get into the brain.

The researchers tested the effects of the new drug on OPCs grown in petri dishes and the animal models of MS using Chan's and Green's methods for tracking remyelination. PIPE-307 blocked the M1R receptor much better than clemastine; prompted OPCs to mature into oligodendrocytes and begin myelinating nearby axons; and it crossed the blood-brain barrier.

But most tellingly, it reversed the degradation seen in a mouse model of MS.

"A drug might seem to work in these abstract scenarios, affecting the right receptor or cell, but the key finding was actual recovery of nervous system function," Chan said.

In 2021, PIPE-307 passed a Phase I clinical trial, demonstrating its safety. It is currently being tested in MS patients in Phase II.

If it succeeds, it could transform how MS is treated.

"Every patient we diagnose with MS comes in with some degree of pre-existing injury," Green said. "Now we might have a chance to not just stop their disease, but to also heal."

More information: Michael M. Poon et al, Targeting the muscarinic M1 receptor with a selective, brain-penetrant antagonist to promote remyelination in multiple sclerosis, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2407974121

https://medicalxpress.com/news/2024-08-drug-clock-multiple-sclerosis.html

New biomaterial regrows damaged cartilage in joints

 Northwestern University scientists have developed a new bioactive material that successfully regenerated high-quality cartilage in the knee joints of a large-animal model.

Although it looks like a rubbery goo, the material is actually a complex network of molecular components, which work together to mimic cartilage's natural environment in the body.

In the new study, the researchers applied the material to damaged cartilage in the animals' knee joints. Within just six months, the researchers observed evidence of enhanced repair, including the growth of new cartilage containing the natural biopolymers (collagen II and proteoglycans), which enable pain-free mechanical resilience in joints.

With more work, the researchers say the new material someday could potentially be used to prevent full knee replacement surgeries, treat degenerative diseases like osteoarthritis and repair sports-related injuries like ACL tears.

The study was published in the Proceedings of the National Academy of Sciences.

"Cartilage is a critical component in our joints," said Northwestern's Samuel I. Stupp, who led the study.

"When cartilage becomes damaged or breaks down over time, it can have a great impact on people's overall health and mobility. The problem is that, in adult humans, cartilage does not have an inherent ability to heal. Our new therapy can induce repair in a tissue that does not naturally regenerate. We think our treatment could help address a serious, unmet clinical need."

A pioneer of regenerative nanomedicine, Stupp is Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering at Northwestern, where he is founding director of the Simpson Querrey Institute for BioNanotechnology and its affiliated center, the Center for Regenerative Nanomedicine.

Stupp has appointments in the McCormick School of Engineering, Weinberg College of Arts and Sciences and Feinberg School of Medicine. Jacob Lewis, a former Ph.D. student in Stupp's laboratory, is the paper's first author.

Control cartilage (stained with safranin) shown with a defect on the upper left side of the image. Credit: Samuel I. Stupp/Northwestern University

What's in the material?

The new study follows recently published work from the Stupp laboratory, in which the team used "dancing molecules" to activate human cartilage cells to boost the production of proteins that build the tissue matrix.

Instead of using dancing molecules, the new study evaluates a hybrid biomaterial also developed in Stupp's lab. The new biomaterial comprises two components: a bioactive peptide that binds to transforming growth factor beta-1 (TGFb-1)—an essential protein for cartilage growth and maintenance—and modified hyaluronic acid, a natural polysaccharide present in cartilage and the lubricating synovial fluid in joints.

"Many people are familiar with hyaluronic acid because it's a popular ingredient in skincare products," Stupp said. "It's also naturally found in many tissues throughout the human body, including the joints and brain. We chose it because it resembles the natural polymers found in cartilage."

Stupp's team integrated the bioactive peptide and chemically modified hyaluronic acid particles to drive the self-organization of nanoscale fibers into bundles that mimic the natural architecture of cartilage.

The goal was to create an attractive scaffold for the body's own cells to regenerate cartilage tissue. Using bioactive signals in the nanoscale fibers, the material encourages cartilage repair by the cells, which populate the scaffold.

Clinically relevant to humans

To evaluate the material's effectiveness in promoting cartilage growth, the researchers tested it in sheep with cartilage defects in the stifle joint, a complex joint in the hind limbs similar to the human knee. This work was carried out in the laboratory of Mark Markel in the School of Veterinary Medicine at the University of Wisconsin–Madison.

Treated cartilage (stained with safranin) showed the defect filled in. Credit: Samuel I. Stupp/Northwestern University

According to Stupp, testing in a sheep model was vital. Much like humans, sheep cartilage is stubborn and incredibly difficult to regenerate. Sheep stifles and human knees also have similarities in weight bearing, size and mechanical loads.

"A study on a sheep model is more predictive of how the treatment will work in humans," Stupp said. "In other smaller animals, cartilage regeneration occurs much more readily."

In the study, researchers injected the thick, paste-like material into cartilage defects, where it transformed into a rubbery matrix. Not only did new cartilage grow to fill the defect as the scaffold degraded, but the repaired tissue was consistently higher quality compared to the control.

A lasting solution

In the future, Stupp imagines the new material could be applied to joints during open-joint or arthroscopic surgeries. The current standard of care is microfracture surgery, during which surgeons create tiny fractures in the underlying bone to induce new cartilage growth.

"The main issue with the microfracture approach is that it often results in the formation of fibrocartilage—the same cartilage in our ears—as opposed to hyaline cartilage, which is the one we need to have functional joints," Stupp said.

"By regenerating hyaline cartilage, our approach should be more resistant to wear and tear, fixing the problem of poor mobility and joint pain for the long term while also avoiding the need for joint reconstruction with large pieces of hardware."

More information: Stupp, Samuel I., A bioactive supramolecular and covalent polymer scaffold for cartilage repair in a sheep model, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2405454121

https://medicalxpress.com/news/2024-08-biomaterial-regrows-cartilage-joints.html

Hospital pneumonia diagnoses uncertain, revised more than half the time

 Pneumonia diagnoses are marked by pronounced uncertainty, an AI-based analysis of over 2 million hospital visits has found.

More than half the time, a pneumonia diagnosis made in the hospital will change from a patient's entrance to their discharge—either because someone who was initially diagnosed with pneumonia ended up with a different final diagnosis, or because a final diagnosis of pneumonia was missed when a patient entered the hospital (not including cases of hospital-acquired pneumonia).

The study describing the new results was published August 6th in Annals of Internal Medicine.

Barbara Jones, MD, MSCI, pulmonary and critical care physician at University of Utah Health and the first author on the study, found the results by searching medical records from more than 100 VA medical centers across the country, using artificial intelligence-based tools to identify mismatches between initial diagnoses and diagnoses upon discharge from the hospital.

More than 10% of all such visits involved a pneumonia diagnosis, either when a patient entered the hospital, when they left, or both.

"Pneumonia can seem like a clear-cut diagnosis," Jones says, "but there is actually quite a bit of overlap with other diagnoses that can mimic pneumonia."

A third of patients who were ultimately diagnosed with pneumonia did not receive a pneumonia diagnosis when they entered the hospital. And almost 40% of initial pneumonia diagnoses were later revised.

The study also found that this uncertainty was often evident in doctors' notes on patient visits; clinical notes on pneumonia diagnoses in the emergency department expressed uncertainty more than half the time (58%), and notes on diagnosis at discharge expressed uncertainty almost half the time (48%). Simultaneous treatments for multiple potential diagnoses were also common.

When the initial diagnosis was pneumonia, but the discharge diagnosis was different, patients tended to receive a greater number of treatments in the hospital, but didn't do worse than other patients as a general rule. However, patients who initially lacked a pneumonia diagnosis, but ultimately ended up diagnosed with pneumonia, had worse health outcomes than other patients.

The new results call into question much of the existing research on pneumonia treatment, which tends to assume that initial and discharge diagnoses will be the same.

Jones adds that doctors and patients should keep this high level of uncertainty in mind after an initial pneumonia diagnosis and be willing to adapt to new information throughout the treatment process. "Both patients and clinicians need to pay attention to their recovery and question the diagnosis if they don't get better with treatment."

More information: Diagnostic Discordance, Uncertainty, and Treatment Ambiguity in Community-Acquired Pneumonia: A National Cohort Study of 115 U.S. Veterans Affairs Hospitals, Annals of Internal Medicine (2024). DOI: 10.7326/M23-2505

https://medicalxpress.com/news/2024-08-hospital-pneumonia-uncertain.html

MSD, Daiichi Sankyo lung cancer ADC starts phase 3

 One of three antibody-drug conjugates licensed by MSD for $4 billion upfront last year has started phase 3 testing in a form of lung cancer.

The first patient has been treated in the pivotal Ideate-Lung02 trial of ifinatamab deruxtecan (I-DXd) in patients with previously treated, extensive-stage small cell lung cancer (SCLC), comparing the ADC to physician's choice of chemotherapy.

I-DXd targets B7-H3, a protein overexpressed on the surface of a wide variety of cancer cells that bind to the CD28 family of receptors, which includes PD-1, targeted by MSD's widely used checkpoint inhibitor Keytruda (pembrolizumab).

There are currently no B7-H3-directed medicines approved for the treatment of any cancer, although there are plenty of companies with designs on bringing one to market. That includes GSK – which licensed a B7-H3 ADC from Hansoh Pharma in a $1.5 billion-plus deal signed last December – and MacroGenics, which has a candidate called vobramitamab duocarmazine (vobra duo) in phase 2 testing.

MacroGenics' programme has been affected by safety issues, including patients deaths, in its clinical trials programme for vobra duo although the company says the side effects are manageable. Meanwhile, other companies with B7-H4-directed ADCs in the pipeline include Myricx and Mabwell.

IDeate-Lung-02 will enrol around 460 patients with relapsed SCLC following disease progression with one prior line of platinum-based chemotherapy, pitting I-DXd against second-line options amrubicin, lurbinectedin, or topotecan. The dual primary endpoints are objective response rate (ORR) and overall survival (OS), with results due in 2027, according to the clinicaltrials.gov listing for the study.

SCLC is the second most common type of lung cancer, accounting for about 15% of all lung cancers, with overexpression of B7-H3 seen in around two-thirds of cases. It is an aggressive tumour, metastasizing rapidly, and has a five-year survival rate of only 3%.

MSD – known as Merck & Co in the US and Canada – acquired rights to HER3-directed ADC patritumab deruxtecan (HER3-DXd), anti-CDH6 candidate raludotatug deruxtecan (R-DXd) and I-DXd last October in a deal with a total potential value of $22 billion.

All hasn't gone entirely to plan, however, as the FDA said in June it was unable to approve HER3-DXd as a third-line or later treatment for adults with locally advanced or metastatic EGFR-mutated non-small-cell lung cancer (NSCLC). The regulator gave manufacturing issues as the reason, however, so the delay could be relatively short.

Meanwhile, MSD and Daiichi Sankyo have also started the REJOICE-Ovarian01 phase 2/3 study for R-DXd in patients with platinum-resistant ovarian cancer, with results due in 2027.

https://pharmaphorum.com/news/msd-daiichi-sankyo-lung-cancer-adc-starts-phase-3

New Wave of Alzheimer’s Therapies Actively Engage the Immune System

 

Active immune therapies hold promise for preventing or slowing disease onset, but some experts warn of potential safety risks.

A handful of companies are developing active immune therapies that may prevent or slow the development of symptoms in Alzheimer’s disease. As both preventatives and therapies, these emerging solutions may have a unique place in the armamentarium against one of the world’s most prevalent illnesses.

The Alzheimer’s Association reports that around 32 million people have Alzheimer’s, the most common form of dementia. That includes more than 5.8 million Americans. Globally, some 10 million new cases of dementia are diagnosed each year.

AC Immune and Vaxxinity both have Phase II clinical trials underway assessing active immune therapies against Alzheimer’s disease. Others in clinical trials include Prothena Biosciences, which holds Fast Track designation for its combined amyloid beta/tau vaccine; Bristol Myers Squibb, which licensed an anti-tau antibody from Prothena that is now in mid-stage clinical trials; and Araclon, which last fall reported on the safety of its vaccine against the Aβ40 peptide.

“The immune system is the best weapon we have,” Mei Mei Hu, CEO of Vaxxinity, told BioSpace.

The notion of an immunotherapy approach to treating Alzheimer’s disease emerged after multiple studies of centenarians, she continued. “When they spun down their blood, scientists found these folks had antibodies against aggregated amyloids. Their immune systems protected them against plaque formation. So, we’re teaching the body to behave like those of high-performing centenarians.”

Active immune therapies are unique in the milieu of Alzheimer’s disease in that they stimulate the immune system to generate antibodies against amyloid beta or tau proteins. They can also be administered as an injection a few times per year, according to researchers studying Vaxxinity’s lead compound, UB-311, writing in eBioMedicine. Consequently, it may be possible to administer active therapies at home.

In contrast, passive immune therapies like Eisai and Biogen’s Leqembi and Eli Lilly’s Kisunla deliver the relevant antibodies, which are infused over one or two hours at a hospital every two to four weeks.

A proprietary report from analyst Sung Jun Hong at BTIG, “Donanemab AdCom Makes it Clear that Patient Stratification is the Road Forward,” suggests this approach “seems likely to be very attractive across neurodegeneration.” Active immune therapy also offers “reduced costs, simpler delivery, and better safety” compared to passive immunotherapy, according to another BTIG report.

A Sheep in Wolf’s Clothing

Vaxxinity’s Active Immunotherapy Medicine (AIM) platform activates CD4+ cells and stimulates B cells. Rather than the “wolf in sheep’s clothing” analogy that commonly applies to other therapies, this is the reverse: “a sheep in wolf’s clothing,” Hu said.

Basically, the AIM platform uses a synthetic version of a pathogenic protein—amyloid beta, in this instance—that the body makes naturally and considers safe. That safe “sheep” is linked to a synthetic peptide that the immune system knows is harmful, triggering the helper T cells to react.

“We ran two trials in Alzheimer’s patients, and 97% of the patients responded,” Hu said. Vaxxinity’s lead compound, UB-311, which targets amyloid beta, reduced cognitive decline by 50% in patients with mild Alzheimer’s. In contrast, the recently approved passive immune therapies Leqembi and Kisunla reduced cognitive decline by 27% and 29%, respectively, on the Clinical Dementia Rating-Sum of Boxes.

Targeting Pathological Proteins

Meanwhile, AC Immune’s approach coats liposomes with antibodies that conform to the structure of the pathological proteins that make up the plaques and tangles in the brain. “This is important because the amyloid beta, tau and alpha synuclein all occur naturally in the body,” Andrea Pfeifer, CEO of AC Immune, told BioSpace. “The only difference between a sick and healthy person [regarding Alzheimer’s disease] is when these proteins change their structure and become pathological.”

AC Immune has three therapies in Phase II clinical testing: one against beta-amyloid plaques, one against tau tangles, and another against alpha-synuclein, a protein implicated in Parkinson’s. “After treating hundreds of patients, we have not seen any safety [concerns] like hemorrhages, edema or ARIA (amyloid-related imaging abnormality), which you see with antibodies,” Pfeifer said.

Not Clear-Cut

But the approach isn’t as clear-cut as it may seem.

When treating Alzheimer’s disease with immunotherapy, “the real problem is the presence of amyloid in blood vessels as well as in the brain,” John Hardy, group leader at the U.K. Dementia Research Institute, told BioSpace. “When [amyloid targeting] antibodies hit the amyloid in the blood vessels, it sometimes causes ARIA. In most cases, that’s not a serious problem, but occasionally it causes hemorrhages. Very occasionally, those hemorrhages have been fatal, particularly among people taking anti-clotting agents.”

Additionally, Hardy said, “Some clinicians are understandably reluctant to give these antibodies to people with high blood pressure or vascular problems. That [constitutes] quite a high proportion of the elderly.”

Active immune therapies face those challenges, plus one more. Because active therapies stimulate the immune system to create antibodies, “If there are side effects, there’s not much you can do about it,” Hardy said, “so people are a bit worried about active immunization.”

Some physicians also remember the first active vaccine clinical trial for Alzheimer’s disease, conducted by Elan Pharmaceuticals. It was halted in 2002 because some of the patients developed meningoencephalitis. It did, nonetheless, suggest the potential of amyloid beta immunotherapy for Alzheimer’s disease.

To that point, in 2019, researchers at the University of Southampton performed a follow-up study of 22 of the 300 original participants in the Elan Pharmaceuticals study. “Patients with Alzheimer’s disease who were actively immunized against amyloid-beta can remain virtually plaque-free for 14 years,” they concluded. Most of those patients, however, had progressed to severe dementia during that time.

Early Diagnosis is Key

The whole concept of active immune therapy relies on early diagnosis, Pfeifer said. Diagnostics using blood-based biomarkers, as well as those in development for biomarkers in saliva and urine, may make diagnosis relatively fast, simple and accurate, even before symptoms appear.

From a public health perspective, if Alzheimer’s disease can be identified presymptomatically, it may be possible for active immune therapy to prevent the disease from advancing.

At that point, Hu added, “treating Alzheimer’s disease [will become] more scalable and accessible because if you can prevent Alzheimer’s disease, there’s not much left to treat.

“People will still develop Alzheimer’s disease, and some may not respond, so there’s a place for multiple therapies,” Hu said. But, for active immune therapy, “It’s a bit of a winner-take-all scenario.”

https://www.biospace.com/drug-development/new-wave-of-alzheimers-therapies-actively-engage-the-immune-system