Alzheimer’s Treatments on the Horizon

Memory disorders expert Zaldy Tan, MD, says new medications
for Alzheimer's disease patients are on the horizon.
Photo by Cedars-Sinai.

As 2022 gets underway, experts in the Cedars-Sinai Departments of Neurology and Neurosurgery are monitoring new Alzheimer’s treatments, while also advancing Cedars-Sinai-led research in noninvasive diagnostic tools for the disease.

Treatments for Alzheimer’s disease—a condition affecting more than 5 million Americans—have been slow to progress. But in mid-2021, the Food and Drug Administration (FDA) approved aducanumab—marketed under the brand name Aduhelm—the first new drug to treat Alzheimer’s disease since 2003.

The once-a-month intravenous infusion is intended to slow cognitive decline in patients in the early stages of the disease by eliminating the amyloid plaque that accumulates in the brain in Alzheimer’s patients. However, studies have not found that eliminating the plaque in the brain reverses cognitive and functional impairment or preserves brain function. Additional questions remain about the treatment’s side effects—including swelling and bleeding in the brain— safety and effectiveness as well as how much of the cost will be shouldered by patients and their families.

The FDA approval, however, spurred momentum in the field, bringing attention to two new therapies—lecanemab and donanemab.

“These two up-and-coming medications are ‘cousins’ of aducanumab because all three drugs target amyloid plaques that form in the spaces between brain cells and are thought to play a central role in Alzheimer’s disease,” said Zaldy Tan, MD, MPH, medical director of the Jona Goldrich Center for Alzheimer’s and Memory Disorders in the Department of Neurology. “What we don’t know yet is whether these new drugs will cause fewer side effects, or whether they will be more effective than aducanumab.”

Will this new superpower molecule revolutionize science?

When scientists discovered DNA and learned how to control it, not only science but society was revolutionized. Today researchers and the medical industry routinely create artificial DNA structures for many purposes, including diagnosis and treatment of diseases.

Now an international research team reports to have created a powerful supermolecule with the potential to further revolutionize science.

The work is published in Nature Communications . Authors are from University of Southern Denmark (DK), Kent State University (USA), Copenhagen University (Denmark), Oxford University (UK) and ATDBio (UK). Lead authors are Chenguang Lou, associate professor, University of Southern Denmark and Hanbin Mao, professor, Kent State University, USA.

"It may allow us to make more advanced nanostructures, for example, for detecting diseases"

Chenguang Lou, associate professor

The researchers describe their supermolecule as a marriage between DNA and peptides.

DNA is one of the most important biomolecules, and so are peptides; peptide structures are used, among other things, to create artificial proteins and various nanostructures.

If you combine these two, as we have, you get a very powerful molecular tool, that may lead to the next generation of nanotechnology; it may allow us to make more advanced nanostructures, for example, for detecting diseases, says corresponding author Chenguang Lou, associate professor at Department of Physics, Chemistry and Pharmacy, University of Southern Denmark.

Scientists move a step closer to understanding the “cold spot” in the cosmic microwave background

Observations for the Dark Energy Survey were carried out, using the Blanco Telescope in the Andes mountains of Chile. Scientists used its data to create a map of dark matter in the region of sky that contains the Eridanus supervoid and CMB Cold Spot.
Photo: Reidar Hahn, Fermilab

After the Big Bang, the universe, glowing brightly, was opaque and so hot that atoms could not form. Eventually cooling down to about minus 454 degrees Fahrenheit (-270 degrees Celsius), much of the energy from the Big Bang took the form of light. This afterglow, known as the cosmic microwave background, can now be seen with telescopes at microwave frequencies invisible to human eyes. It has tiny fluctuations in temperature that provide information about the early universe.

Now scientists might have an explanation for the existence of an especially cold region in the afterglow, known as the CMB Cold Spot. Its origin has been a mystery so far but might be attributed to the largest absence of galaxies ever discovered.

Scientists used data collected by the Dark Energy Survey to confirm the existence of one of the largest supervoids known to humanity, the Eridanus supervoid, as reported in a paper published in December 2021. This once-hypothesized but now-confirmed void in the cosmic web might be a possible cause for the anomaly in the CMB.

High Levels of PFAS Found in Anti-Fogging Sprays and Cloths

The anti-fogging sprays and cloths many people use to prevent condensation on their eyeglasses when wearing a mask or face shield may contain high levels of per- and polyfluorinated alkyl substances (PFAS), a new Duke University-led study finds.

The researchers tested four top-rated anti-fogging sprays and five top-rated anti-fogging cloths sold on Amazon. They found all nine products contained fluorotelomer alcohols (FTOHs) and fluorotelomer ethoxylates (FTEOs), two types of PFAS that largely have flown under the scientific radar until now.

Exposure to some PFAS, particularly perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), is associated with impaired immune function, cancer, thyroid disease, and other health disorders. Mothers and young children may be especially vulnerable to the chemicals, which can affect reproductive and developmental health.

“Our tests show the sprays contain up to 20.7 milligrams of PFAS per milliliter of solution, which is a pretty high concentration,” said Nicholas Herkert, a postdoctoral researcher at Duke’s Nicholas School of the Environment, who led the study.

Because FTOHs and FTEOs have received relatively little study, scientists don’t yet know what health risks they might pose, Herkert noted, but research suggests that once FTOHs have been inhaled or absorbed through the skin, they could break down in the body to PFOA or other long-lived PFAS substances that are known to be toxic. Additionally, the FTEOs used in all four spray mixtures that were analyzed in the new study exhibited significant cell-altering cytotoxicity and adipogenic activity in lab tests, he said.

Research uncovers key system in E. coli that could lead to new antibiotics

In addition to using the structure as a platform to generate antibiotics,
researchers can also use it to design new sensors of molecules of interest,
says Dr. Luis Rogelio (Roger) Cruz-Vera.
Image Credit: Michael Mercier | UAH

Research led by the University of Alabama in Huntsville (UAH) has for the first time identified the precise genetic operational structure of a key system in Escherichia coli (E. coli) bacteria, opening the door to possible new antibiotics to treat the infections it causes.

“The gene that we studied is involved in producing a bacterial hormone that is important for bacterial colonization. This hormone induces the production of sticky substances used by bacteria to adhere to inert surfaces, as well as plants and animal tissues,” says Dr. Luis Rogelio (Roger) Cruz-Vera, an associate professor in the Department of Biological Sciences at UAH, a part of the University of Alabama System.

“Our new structure will be used in future studies to obtain compounds that can modulate the production of this hormone in bacteria, reducing bacterial colonization by altering the bacterial cell’s capacity for attachment to surfaces and reduce communication with other cells.”

Most infectious E. coli cases are mild and result in vomiting, diarrhea, cramps, and fatigue, but some strains can cause severe illness and even life-threatening complications.

In 2015, Dr. Cruz-Vera teamed with Dr. Emily Gordon and Dr. Arnab Sengupta, both of whom were doctoral students in UAH’s Biotechnology Science and Engineering program at the time, and whose work during their graduate tenure produced the genetic and biochemical assays used in the research paper the trio wrote with other collaborators. The research was funded by the National Science Foundation.

Study finds Rwandan genocide chemically modified the DNA of victims and victims’ offspring

USF Professor Derek Wildman and Clarisse Mussanabaganwa,
visiting scholar from the University of Rwanda,
conduct research at USF.

Scientists with the USF Genomics program and the Center for Global Health and Infectious Disease Research have taken a significant step in providing the people of Rwanda the scientific tools they need to help address mental health issues that stemmed from the 1994 genocide of the Tutsi ethnic group.

In a first-of-its-kind study, Professors Monica Uddin and Derek Wildman of the College of Public Health looked at the entire genomes of Tutsi women who were pregnant and living in Rwanda at the time of the genocide and their offspring and compared their DNA to other Tutsi women pregnant at the same time and their offspring, who were living in other parts of the world.

In the study published in Epigenomics, they found that the terror of genocide was associated with chemical modifications to the DNA of genocide-exposed women and their offspring. Many of these modifications occurred in genes previously implicated in risk for mental disorders such as PTSD and depression. These findings suggest that, unlike gene mutations, these chemical “epigenetic” modifications can have a rapid response to trauma across generations.

“Epigenetics refers to stable, but reversible, chemical modifications made to DNA that help to control a gene’s function,” Uddin said. “These can happen in a shorter time frame than is needed for changes to the underlying DNA sequence of genes. Our study found that prenatal genocide exposure was associated with an epigenetic pattern suggestive of reduced gene function in offspring.”

An overuse of road salt in the winter has potentially harmful effects for everything from wildlife to groundwater

The winter months can bring dicey travel conditions, but those can be made safer with shovels, plows, and deicers like road salts. For road salts, a little can go a long way in improving safety, but its use is not without consequences. Researchers from the College of Agriculture, Health and Natural Resources and the College of Liberal Arts and Sciences are working to better understand the numerous environmental impacts of using too much salt on roads and walkways.

Bigger Frogs, More Mosquitos

Department of Natural Resources and the Environment researcher Tracy Rittenhouse and her group are investigating the effects road salts on amphibians.

“Previous research showed that tadpoles tend to metamorph larger in size from salty wetlands and high salinity conditions,” Rittenhouse says. “Generally, we think larger size as a good thing but we’re not sure why they’re larger or how they might be different physiologically.”

Rittenhouse explains that frogs starting life in saltier conditions, though larger, don’t seem to have any advantages later in life, whereas frogs from lower salt conditions started life smaller but grew much faster and larger over time. These results show that not only are amphibians amazingly tolerant to salt, but that we have much to learn. Despite the quantities of salt entering wetland environments, this resilience is why we have not seen massive declines in amphibian populations, says Rittenhouse.

Another experiment completed by an undergraduate student in her lab group showed that juvenile frogs not only detect if soil is salty, they will consistently avoid those conditions.

“That project opened up this whole arena of what we really should be looking at is the juvenile and adult frogs and how they might be responding to salinity in the terrestrial environment,” she says.

Researchers find low oxygen and sulfide in the oceans played greater role in ancient mass extinction

Seth Young’s research group collecting and describing limestone samples from a field site in the Roberts Mountains, Nevada.
Credit: Anders Lindskog/Florida State University

Florida State University researchers have new insight into the complicated puzzle of environmental conditions that characterized the Late Ordovician Mass Extinction (LOME), which killed about 85% of the species in the ocean.

Their work on the 445-million-year-old mass extinction event was published online in the journal AGU Advances.

“We found that reducing conditions — with low to no oxygen and little to no hydrogen sulfide levels — are probably playing a much more important role than we previously thought,” said lead author Nevin Kozik, a doctoral candidate in the Department of Earth, Ocean and Atmospheric Science and researcher at the FSU-headquartered National High Magnetic Field Laboratory. “If you imagine a pie chart of the causes of this extinction, we’re increasing that wedge that signifies oxygen deficiency, which is happening in concert with a cooling climate and widespread habitat loss due to sea-level change.”

The research is the first study to use measurements of multiple elements from several sites to examine the conditions that led to the LOME, the second-largest extinction event in the Earth’s history and the only mass extinction to occur during what are called icehouse conditions, when Earth’s climate is cold enough at the poles to support ice sheets year-round.

What you need to know about Pfizer’s anti COVID-19 drug Paxlovid

The FDA has authorized Pfizer’s Paxlovid for emergency use* to treat COVID-19 patients at high risk of hospitalization or death. Paxlovid can slow the replication of the virus that causes COVID, but it has the potential for dangerous interactions with drugs commonly prescribed for diabetes, heart disease, and many other conditions.

High risk patients are often those who have not been vaccinated, and/or have a number of comorbidities (additional, chronic health problems) such as hypertension, diabetes, hyperlipidemia, depression, and cancer.

Patients already taking multiple drugs to control chronic diseases, could be effected by harmful drug interactions between the their current drugs and Paxlovid. Awareness of potential drug-drug interactions may help to avoid severe adverse drug reactions and improve efficacy of Paxlovid’s anti-COVID-19 activity.

Paxloid contains two medicines in two separate tablets, nirmatrelvir and ritonavir. The drug’s anti-COVID-19 activity relies on the inhibition of SARS-CoV-2 Mpro enzyme activity by nirmatrelvir, which results in inhibition of virus replication. Nirmatrelvir is a substrate of cytochrome P450 CYP3A4 for metabolism.

Ritonavir is an HIV drug that inhibits CYP3A4 and slows the metabolism of Nirmatrelvir, therefore enhancing efficacy of anti-virus activity of Nirmatrelvir.

Spleen function discovery could lead to better treatments for infectious diseases

An advanced fluorescent microscopy image of the complex networks of stromal cells that construct the spleen and support immune responses.
Image: Professor Scott Mueller

Researchers at the Peter Doherty Institute for Infection and Immunity (Doherty Institute) have discovered a new gene that plays an important role in the way the spleen functions, potentially leading to new treatments for infectious diseases.

The study, published in Science Immunology, also uncovered multiple new spleen cells and revealed the distinct way they respond in order to fight off different infections.

The spleen plays a key role in the immune responses that protect the body against various diseases and infections such as virus infections, malaria and sepsis, and also plays a key role in the immune response to vaccines. However, it has not been known how the spleen functions to support this response.

University of Melbourne Professor Scott Mueller, a Laboratory Head at the Doherty Institute and lead author on the paper, explained that while it is known the spleen is made up of various networks of cells called fibroblasts, a clear picture of how these cells are constructed and function, was lacking.

“Using novel biological tools and next generation sequencing, we were able to examine precisely how specialized types of fibroblast cells dictate how the spleen works to protect against infections,” Professor Mueller explained.