Tag Archives: Alzheimer’s

Biogen Nabs Speedy FDA Review For Alzheimer’s Drug

Biogen’s aducanumab is inching closer to an FDA decision. The Big Biotech, along with partner Eisai, announced  that the FDA accepted its regulatory submission for aducanumab, its once-failed Alzheimer’s drug—with priority review to boot. The agency expects to decide the fate of the treatment by March 7. Along the way, it will hold an advisory committee meeting. It has not set a date for the meeting, but Jefferies analyst Michael Yee expects it sometime in the first quarter of 2021.

The FDA’s acceptance of the aducanumab BLA with Priority Review is an important step in the path to potentially having a treatment that meaningfully changes the course of Alzheimer’s disease,” said Michel Vounatsos, Chief Executive Officer at Biogen.

How the FDA rules on aducanumab will show how far the FDA and its commissioner, Stephen Hahn, M.D., are willing to diverge from its established approval standards. Under U.S. law, companies need to show “substantial evidence of effectiveness to win approval.

Source: https://investors.biogen.com/

https://www.fiercebiotech.com/

Antibodies + Immunotherapy Result In Complete Elimination Of Tumors

Immunotherapy has revolutionized cancer treatment by stimulating the patient’s own immune system to attack cancer cells, yielding remarkably quick and complete remission in some cases. But such drugs work for less than a quarter of patients because tumors are notoriously adept at evading immune assault.

A new study in mice by researchers at Washington University School of Medicine in St. Louis has shown that the effects of a standard immunotherapy drug can be enhanced by blocking the protein TREM2, resulting in complete elimination of tumors. The findings, which are published in the journal Cell, point to a potential new way to unlock the power of immunotherapy for more cancer patients.

Immune cells infiltrate a human tumor in the four colorized images above. In a mouse study, researchers at Washington University School of Medicine in St. Louis have found that an antibody that targets the protein TREM2 empowers tumor-destroying immune cells and improves the effectiveness of cancer immunotherapy.

Essentially, we have found a new tool to enhance tumor immunotherapy,” said senior author Marco Colonna, MD, the Robert Rock Belliveau, MD, Professor of Pathology. “An antibody against TREM2 alone reduces the growth of certain tumors, and when we combine it with an immunotherapy drug, we see total rejection of the tumor. The nice thing is that some anti-TREM2 antibodies are already in clinical trials for another disease. We have to do more work in animal models to verify these results, but if those work, we’d be able to move into clinical trials fairly easily because there are already a number of antibodies available.”

T cells, a kind of immune cell, have the ability to detect and destroy tumor cells. To survive, tumors create a suppressive immune environment in and around themselves that keeps T cells subdued. A type of immunotherapy known as checkpoint inhibition wakes T cells from their quiescence so they can begin attacking the tumor. But if the tumor environment is still immunosuppressive, checkpoint inhibition alone may not be enough to eliminate the tumor.

An expert on the immune system, Colonna has long studied a protein called TREM2 in the context of Alzheimer’s disease, where it is associated with underperforming immune cells in the brain. Colonna and first author Martina Molgora, PhD, a postdoctoral researcher, realized that the same kind of immune cells, known as macrophages, also were found in tumors, where they produce TREM2 and promote an environment that suppresses the activity of T cells.

When we looked at where TREM2 is found in the body, we found that it is expressed at high levels inside the tumor and not outside of the tumor,” Colonna said. “So it’s actually an ideal target, because if you engage TREM2, you’ll have little effect on peripheral tissue.”

Colonna and Molgora — along with colleagues Robert D. Schreiber, PhD, the Andrew M. and Jane M. Bursky Distinguished Professor; and William Vermi, MD, an immunologist at the University of Brescia — set out to determine whether inhibiting TREM2 could reduce immunosuppression and boost the tumor-killing powers of T cells. As part of this study, the researchers injected cancerous cells into mice to induce the development of a sarcoma.

The mice were divided into four groups. In one group, the mice received an antibody that blocked TREM2; in another group, a checkpoint inhibitor; in the third group, both; and the fourth group, placebo. In the mice that received only placebo, the sarcomas grew steadily. In the mice that received the TREM2 antibody or the checkpoint inhibitor alone, the tumors grew more slowly and plateaued or, in a few cases, disappeared. But all of the mice that received both antibodies rejected the tumors completely. The researchers repeated the experiment using a colorectal cancer cell line with similarly impressive results.

Source: https://medicine.wustl.edu/

A Simple Blood Test To Find Early Signs Of Alzheimer’s

A new study found that a simple blood test can detect beta-amyloid protein buildup in a person’s brain years before Alzheimer’s disease symptoms appearHigh amounts of beta-amyloid can clump together and form plaques on the brain, which is strongly associated with Alzheimer’s disease. Other research has found that amyloid plaques can appear as early as 20 years before the first sign of Alzheimer’s symptoms, such as cognitive decline and memory loss.

In the study, 158 adults in their 60s and 70s — most of whom had normal cognitive function — underwent a PET scan to spot amyloid plaque in the brain, and a blood test to measure beta-amyloid in the body. The blood test looked for two forms of beta-amyloid protein: beta-amyloid 42 and beta-amyloid 40. When beta-amyloid begins to build up, the ratio between the two proteins changes, and the blood test detects this.

The researchers labeled each blood test result as either amyloid positive or negative. They then compared them with the PET scans. They found that the PET scans confirmed the blood test results  88% of the time. When other risk factors were included, such as age and the appearance of the gene variant ApoE4 (which also is linked to a higher risk for Alzheimer’s), the test’s accuracy rose to 94%.

While there is some debate as to whether amyloid plaque actually causes Alzheimer’s, a simple blood test that indicates you may be at a higher risk of the disease would be one more reason to adopt lifestyle changes. The researchers added that they expect the blood test to be available within a few years.

The results were published online Aug. 1, 2019, by the journal Neurology.

Source: https://www.health.harvard.edu/

Coronavirus Has Killed Much Less People In The US Than Heart Disease

The coronavirus has killed over 100,000 people in the US in just 4 months. This chart shows how that compares to other common causes of death.

Source: https://www.businessinsider.fr/

Biomarker detects Alzheimer’s decades before symptoms appear

Two new studies, published in the journal The Lancet Neurology, are suggesting increasing levels of a particular brain protein, detected in blood and spinal fluid, could be the earliest sign of neurodegenerative diseases such as Alzheimer’s and Huntington’sNeurofilament light chain (NfL) is a protein that is released as a result of brain cell damage. It is one of the most promising early-stage biomarkers for a variety of neurodegenerative diseases, including Parkinson’s disease, ALS and multiple sclerosis.

It is commonly suspected that the neurodegeneration associated with many of these devastating diseases begins years, or even decades, before clinical symptoms finally appear. And on the back of many failed drug trials, researchers are beginning to believe that once symptoms eventually appear much of the neurological damage could be irreversible. So finding ways to catch these diseases at the earliest possible point will be vital in delivering effective treatments.

Huntington’s disease is a heritable neurodegenerative disease with no cure. Clinical symptoms can begin appearing at any age, however, generally the condition doesn’t become apparent until middle-age, and once symptoms do appear a gradual decline to death takes place over about 20 years. Researchers have homed in on a number of clues, both behavioral and physiological, to detect the earliest stages of the disease but a new study from an international team of researchers is suggesting NfL levels in cerebrospinal fluid (CSF) could detect Huntington’s neurodegeneration up to 24 years before the clinical onset of the disease.

Other studies have found that subtle cognitive, motor and neuropsychiatric impairments can appear 10-15 years before disease onset,” explains co-first author on the study, Rachael Scahill. “We suspect that initiating treatment even earlier, just before any changes begin in the brain, could be ideal, but there may be a complex trade-off between the benefits of slowing the disease at that point and any negative effects of long-term treatment.

The new study presents the most detailed investigation ever conducted into early-stage Huntington’s disease biomarkers in a young cohort of patients. The study recruited 64 subjects, all carrying the Huntington’s gene mutation, and all estimated to be an average of 24 years ahead of the disease onset. The cohort was subjected to a large assortment of tests, with the researchers searching for an early sign of the disease. Elevated CSF NfL levels, compared to a control group, turned out to be the most prominent early sign of the disease. The researchers suggest this is the earliest sign of neuronal damage related to Huntington’s disease ever detected, and offers scientists a new biomarker to use to recruit subjects for clinical trials testing new preventative treatments.

We have found what could be the earliest Huntington’s-related changes, in a measure which could be used to monitor and gauge effectiveness of future treatments in gene carriers without symptoms,” says co-first author Paul Zeun. In the Huntington’s study it was primarily NfL levels in spinal fluid that presented as the most effective early diagnostic biomarker of the disease. However, another new study examining NfL levels in relation to Alzheimer’s disease, is suggesting a more simple blood test could be useful in detecting NfL changes for that particular neurodegenerative disease.

A study published early in 2019 suggested increasing NfL levels in blood samples could detect Alzheimer’s disease around a decade before clinical symptoms appear. Yakeel Quiroz, from Harvard Medical School, wondered how early this biomarker could indicate the neurodegenerative disease.

We wanted to determine the earliest age at which plasma NfL levels could distinguish individuals at high risk of Alzheimer’s,” says Quiroz, co-first author on the study.

The researchers examined more than 1,000 subjects with a particular familial genetic mutation that makes them at a high risk of developing Alzheimer’s disease. The cohort was aged between eight and 75 years, and the results remarkably revealed increasing NfL levels could be detected at the early age of 22. The estimated median age of onset for mild cognitive impairment associated with this form of familial Alzheimer’s disease is 44, so the researchers say the biomarker could indicate the very earliest stage of neurodegeneration linked to the disease, 22 years before symptoms appear.

Source: https://newatlas.com/

How To Prevent The Formation Of Alzheimer’s Plaques

People who are affected by Alzheimer’s disease have a specific type of plaque, made of self-assembled molecules called β-amyloid (Aβ) peptides, that build up in the brain over time. This buildup is thought to contribute to loss of neural connectivity and cell death. Researchers are studying ways to prevent the peptides from forming these dangerous plaques in order to halt development of Alzheimer’s disease in the brain.

In a multidisciplinary study, scientists at the U.S. Department of Energy’s (DOE) Argonne National Laboratory, along with collaborators from the Korean Institute of Science and Technology (KIST) and the Korea Advanced Institute of Science and Technology (KAIST), have developed an approach to prevent plaque formation by engineering a nano-sized device that captures the dangerous peptides before they can self-assemble.


Transmission Electron Microscopy (TEM) images of Aβ peptide samples in the presence of the Aβ nanodevices (scale bar: 200 nm). The lack of grains in the image indicates the effectiveness of the nanodevice in trapping the peptides

We’ve taken building blocks from nanotechnology and biology to engineer a high-capacity cage’ that traps the peptides and clears them from the brain.” — Elena Rozhkova, scientist, Center for Nanoscale Materials

The β-amyloid peptides arise from the breakdown of an amyloid precursor protein, a normal component of brain cells,” said Rosemarie Wilton, a molecular biologist in Argonne’s Biosciences division.In a healthy brain, these discarded peptides are eliminated.”

In brains prone to the development of Alzheimer’s, however, the brain does not eliminate the peptides, leaving them to conglomerate into the destructive plaques.

The idea is that, eventually, a slurry of our nanodevices could collect the peptides as they fall away from the cells — before they get a chance to aggregate,” added Elena Rozhkova, a scientist at Argonne’s Center for Nanoscale Materials (CNM), a DOE Office of Science User Facility.

Source: https://www.anl.gov/

Genetic Test To Detect Earlier Alzheimer’s

A new study published in the journal Epigenetics in February 2020 reports that changes in the methylation status of the Presenilin 1 (PSEN1) gene could help diagnose Alzheimer’s disease (AD) earlier. This study shows for the first time that methylation of this gene is a common feature in AD.

AD is a widespread dementia disorder, involving the loss of cognitive skills such as thinking, making decisions, remembering things in connection, and learning. It affects almost 50 million people the world over, mostly over the age of 60 years but a significant percentage at ages below 50 years. Furthermore, this is only a fourth of all cases, because most patients go undiagnosed.

 

The progressive and incurable nature of this disorder makes it difficult to bear for both the patient and the caregivers. The disease inevitably progresses to the point where complete care is required. Currently, available medications must be given early to have the highest odds of successfully delaying the onset of severe cognitive loss.

The PSEN1 gene is part of a protease complex that catalyzes a process called regulated intramembrane proteolysis. It is important in AD because it is responsible for cleaving the beta-amyloid fragment from the parent AβPP molecule. It is one of several polymorphic genes that regulate normal embryonic regulation but also promote the risk of AD.

Epigenetic modification is an important way to regulate gene activity in the body and can be triggered by environmental factors, including specific lifestyle and nutritional factors. The addition of methyl groups to the DNA (mostly to the cytosine) outside the actual genetic code, called methylation, is a well-known epigenetic modification. Methylation is typically a method to silence or downregulate the associated gene.

Earlier animal studies have shown that the PSEN1 gene can be downregulated, causing a condition very like AD.  However, little research has been done epigenetic modification of the human PSEN1 gene. It is established that people with AD already show altered PSEN1 behavior. The current study is the first to record the frequent occurrence of DNA methylation at this gene in humans with AD.

Source: https://www.news-medical.net/

Molecular ‘Switch’ Reverses Chronic Inflammation And Aging

Chronic inflammation, which results when old age, stress or environmental toxins keep the body’s immune system in overdrive, can contribute to a variety of devastating diseases, from Alzheimer’s and Parkinson’s to diabetes and cancer.

Now, scientists at the University of California, Berkeley, have identified a molecularswitch” that controls the immune machinery responsible for chronic inflammation in the body. The finding, which appears online  in the journal Cell Metabolism, could lead to new ways to halt or even reverse many of these age-related conditions.

My lab is very interested in understanding the reversibility of aging,” said senior author Danica Chen, associate professor of metabolic biology, nutritional sciences and toxicology at UC Berkeley. “In the past, we showed that aged stem cells can be rejuvenated. Now, we are asking: to what extent can aging be reversed? And we are doing that by looking at physiological conditions, like inflammation and insulin resistance, that have been associated with aging-related degeneration and diseases.”

In the study, Chen and her team show that a bulky collection of immune proteins called the NLRP3 inflammasome — responsible for sensing potential threats to the body and launching an inflammation response — can be essentially switched off by removing a small bit of molecular matter in a process called deacetylation.

Overactivation of the NLRP3 inflammasome has been linked to a variety of chronic conditions, including multiple sclerosis, cancer, diabetes and dementia. Chen’s results suggest that drugs targeted toward deacetylating, or switching off, this NLRP3 inflammasome might help prevent or treat these conditions and possibly age-related degeneration in general.

This acetylation can serve as a switch,” Chen said. “So, when it is acetylated, this inflammasome is on. When it is deacetylated, the inflammasome is off.”

Source: https://news.berkeley.edu/

Alzheimer’s Breakthrough Likely Within Five Years

The head of the Trump administration’s medical research institution predicted the United States would be closer to slowing the progression of Alzheimer’s disease within the next five years.

Will we have a cure this year? Probably not,” National Institutes of Health Director Francis Collins said on New Year’s Eve in an interview with Newsmakers on C-SPAN. “Will we have a way to figure out how to slow the disease in the next five years? I believe we will, but it is going to take every bit of energy, creativity, determination, and resources possible to get there.

Collins, who has led the NIH for more than a decade, didn’t specify a figure for how much funding would be needed to make progress on Alzheimer’s, the sixth-leading cause of death in the U.S. Research on another leading killer, cancer, has surpassed $5 billion in funding for years, and researchers have been able to develop new ways to address certain types.

In its latest spending bill, Congress increased NIH funding for dementia research, including Alzheimer’s, by $350 million, bringing the total amount devoted to the cause to $2.8 billion. The budget is four times what it was six years ago. NIH conducts research in-house and provides grants to outside scientists. “We will put every dime of that to good use,” Collins said.

Despite some increases in funding several years in a row, there’s still no way to cure the disease or to slow it, leaving public health experts and policymakers concerned about how the U.S. will care for the 14 million adults who are predicted to have Alzheimer’s by 2050, as well as for their caregivers.

For years, scientists were primarily focused on the theory that if they could get rid of a protein buildup in the brain called “amyloid,” then they could get rid of Alzheimer’s disease. Their research, however, came up dry. Now, Collins noted in the interview, scientists are looking at a lot of different approaches to addressing Alzheimer’s. “We have hedged our bets at the NIH over the course of the last five or six years to look in every nook and cranny,” Collins said.

Source: https://www.washingtonexaminer.com/

Alzheimer’s May Be Caused By Dental Infection

In a new study scientists reveal yet another reason to keep up on dental hygiene. Bacteria that cause a common yet largely preventable gum infection may also play a role in Alzheimer’s disease. The discovery also offers hope for a treatment that could slow neurodegeneration.

There were many clues in the [features of Alzheimer’s disease] that an infection is at work,” said Casey Lynch, an entrepreneur and co-founder of Cortexyme, a biotech company headquartered at the Verily Life Sciences campus in South San Francisco, who led the new research. “Many of the genetic risk factors for Alzheimer’s are related to immune system function,” she added, which suggests “immune system dysfunction might put people more at risk.

Alzheimer’s disease, an irreversible and progressive brain disorder that leads to memory loss and diminished thinking skills, affects at least 5 million Americans. Clumps of a brain protein known as amyloid plaques are a hallmark sign of the disease. Billions of research dollars have gone towards finding a treatment that destroys these mind-robbing masses. But there’s still no cure.

Not enough people are asking what is upstream of the plaques … and [brain] inflammation,” said Lynch, who has a background in Alzheimer’s research and was frustrated by the string of failed therapies for the disease. Nearly six years ago, Lynch received a call from Stephen Dominy, a psychiatrist at the University of California, San Francisco, who had studied the link between HIV and dementia.

I think I’ve found a bacterial cause of Alzheimer’s,” Dominy, who co-founded Cortexyme with Lynch and now serves as the company’s Chief Scientific Officer, told her. Dominy had spent about 15 years searching for infections that might lead to Alzheimer’s until evidence for a bacterium known as P. gingivalis became “undeniable,” according to Lynch. P. gingivalis causes periodontitis, an infection that destroys the gums and can lead to tooth loss.

When the team examined the brains and cerebrospinal fluid of Alzheimer’s patients, they found DNA from the bacterium. They also discovered bacterial enzymes called gingipains that destroy brain cells were present, too. And when they watched P. gingivalis infections play out in mice, it triggered neurodegeneration in the hippocampus, a brain structure central to memory. It also led to Alzheimer’s hallmark amyloid beta plaque production and inflammation, the researchers discovered.

The scientists then designed and created a new molecule that blocks the gingipain enzymes. The antibiotic reduced the amount of bacteria in infected mice and stopped the formation of amyloid beta plaques while reducing inflammation, the team reports Wednesday in the journal Science Advances.

Source: https://www.discovermagazine.com/