Controlled, localized delivery of blood thinner may improve blood clot treatment

 Heparin has long been used as a blood thinner, or anticoagulant, for patients with blood clotting disorders or after surgery to prevent complications. But the medication remains difficult to dose correctly, potentially leading to overdosing or underdosing.

A team of Penn State researchers combined heparin with a protein fragment, peptide, to slow down the release of the drug and convey the medication directly to the site of a clot. They published their findings in the journal Small.

"We wanted to develop a material that can gradually deliver heparin over time rather than the current iteration that gets cleared from the body in a couple of hours," said corresponding author Scott Medina, Penn State associate professor of biomedical engineering. "We also wanted to deliver the drug through the skin instead of through an IV."

When mixed, positively charged peptides and negatively charged heparin bind to create a nanogranular paste that can be injected under the skin, forming a cache of material that is then diffused in the circulatory system and travels to blood clots when they appear. The turbulent flow of fluid near a blood clot triggers the two materials to separate, allowing heparin to begin its anticoagulating action.

"The peptide is ideal for pairing with heparin because it essentially blocks heparin's action until it is needed in the body," said Atip Lawanprasert, doctoral student in biomedical engineering and first author on the paper. "The peptide also has some anticoagulating properties on its own: It binds to platelets in the blood, enabling action at the clotting site."

Without an added bonding agent, heparin applies its anti-clotting properties indiscriminately, not just at blood clot sites, and clears quickly, its half-life only 60 to 90 minutes. Using preclinical animal trials, researchers determined that the addition of peptide allows for a dramatic increase of heparin's half-life, to up to nearly 24 hours.

"The peptide increases heparin's effects by more than ten times longer than what is currently being used," Medina said. "The increased half-life allows for sustained treatments for patients, less medication waste and more accurate dosing. Eventually, this could allow the medication to be injected under the skin just once a day, rather than an all-day IV drip."

Next, researchers plan to replicate the study in a clinical setting, as well as study the effect of the medication's toxicity in the body if administered over multiple days.

More information: Atip Lawanprasert et al, Heparin‐Peptide Nanogranules for Thrombosis‐Actuated Anticoagulation, Small (2022). DOI: 10.1002/smll.202203751

https://medicalxpress.com/news/2023-01-localized-delivery-blood-thinner-clot.html

New tau regulators and therapeutic targets for neurodegenerative disorders discovered

 Neurodegenerative diseases affect millions of people worldwide and as our life expectancy increases, more individuals are expected to be affected in the coming decades. Tauopathies such as Alzheimer's disease are a class of neurodegenerative disorders involving an accumulation of tau proteins, which eventually results in massive loss of brain cells. There is little consensus about the underlying causes and no effective treatments are available currently for these disorders.

In a current study published in Neuron the goal of researchers at Baylor College of Medicine and Texas Children's Hospital was to conduct an unbiased screen to find genes whose inhibition can reduce the levels of tau protein. They identified new tau regulators that can serve as viable and effective therapeutic targets for Alzheimer's disease and other tauopathies.

This study was led by Dr. Huda Zoghbi, professor of molecular and human genetics and neuroscience at Baylor and founding director of the Jan and Dan Duncan Neurological Research Institute (Duncan NRI) at Texas Children's. The study involved multidisciplinary collaborations with other Duncan NRI faculty, Drs. Juan Botas and Zhandong Liu.

A cross-species screen reveals three new tau regulators

First, the Liu lab performed computational modeling and prediction analysis of the known 17,000 human genes and generated a compendium of 6,600 genes that were deemed to be "druggable," meaning the proteins produced by these genes can be modified by chemical compounds.

"Next, we used a cross-species approach involving mammalian cells and fruit flies to comb through this large collection to find genes that impact tau levels both in mammals and fruit flies," said Dr. Jiyoen Kim, assistant professor of neuroscience in the Zoghbi lab and lead author of the study.

In both screens, the activity of the genes was reduced using RNA interference technology, with a small subset of genes targeted by CRISPR technology in the cell-based screen.

"Our strategy of performing parallel screens in mammalian cells and fruit flies allowed us to select targets that showed up as top hits in both species," said co-author Dr. Ismael Al-Ramahi, assistant professor of molecular and human genetics at Baylor and a member of the Duncan NRI.

This approach led them to 11 new validated tau regulators. Of these, three—USP 7, RNF130 and RN149—converged on the ubiquitin protein degradation pathway. The team further investigated these proteins looking to understanding how their regulating of the ubiquitin pathway will likely reveal mechanistic insights into tau degradation.

USP7, RNF130 and RNF149 regulate tau levels via the CHIP system

The team discovered that USP7 stabilizes tau by protecting it from CHIP-mediated degradation. They also found that RNF130 and RNF149 decrease the levels of the tau degrader (CHIP). To test if these target genes can regulate CHIP and tau levels in the brain, the team turned off their expression in adult mice that overexpress mutant tau.

"Turning off the expression of USP7, RNF130 or RNF149 in adult mice with tauopathy increased CHIP level and reduced tau proteins," Kim said. "We also saw a decrease in other tell-tale signs of tau-mediated damage and neuro-inflammation. Most excitingly, these mice performed as well as age-matched normal mice in tasks that required learning and memory—a strong indicator that increasing CHIP levels in addition to a concomitant reduction in tau levels can improve neuronal and overall brain function in these mice."

Although these three proteins have never been linked with each other before, it is notable that their functions converged on CHIP, which highlights its central role in maintaining tau levels in check.

"We rationalized that identifying tau regulators that can be inhibited by small-molecule drugs will be worthwhile given the likelihood that treatments to prevent dementia are best initiated in the pre-symptomatic phase and are likely to go on for decades," Zoghbi said. "We are excited to have found three targets that reduce tau level and show marked improvements in disease characteristics and learning and memory in animal models. This discovery opens the exciting possibility of leveraging small-molecule inhibitors to lower tau levels and hopefully, prevent memory deficits in those at risk for Alzheimer's disease and other tauopathies."

More information: Jiyoen Kim et al, Evolutionarily conserved regulators of tau identify targets for new therapies, Neuron (2023). DOI: 10.1016/j.neuron.2022.12.012

https://medicalxpress.com/news/2023-01-tau-therapeutic-neurodegenerative-disorders.html

Inflammatory trigger a new clue in Alzheimer's

 Scientists from The University of Texas Health Science Center at San Antonio (UT Health San Antonio) today reported that an inflammatory trigger like one present during viral infections is elevated in Alzheimer's disease and progressive supranuclear palsy, a rare brain disorder.

"We have identified a new trigger of brain inflammation in these disorders," said Elizabeth Ochoa, study author from UT Health San Antonio. The finding published in Science Advances is novel for this reason, she said.

Ochoa, a recent doctoral graduate, and her mentor, Bess Frost, Ph.D., study senior author, are investigators with the Sam and Ann Barshop Institute for Longevity and Aging Studies, the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, and the Department of Cell Systems and Anatomy at UT Health San Antonio. Frost is the Bartell Zachry Distinguished Professor for Research in Neurodegenerative Disorders.

Alzheimer's disease and progressive supranuclear palsy are marked by toxic deposits of a protein called tau. Their research found that tau-induced "jumping genes"—which can relocate or copy themselves to other locations in the genome—form double-stranded RNA. This abnormal RNA mimics the inflammatory trigger that is also present in viral infections.

"Transposable elements—the so-called jumping genes—are a new area of interest in understanding Alzheimer's disease. Our study provides new insights into how they can drive the disease process in addition to their ability to jump," Ochoa said. "These double-stranded RNAs look like a virus to the immune system even though the jumping genes are a part of our normal genome."

The researchers detected accumulation of double-stranded RNA in postmortem brain tissue from patients with Alzheimer's disease and progressive supranuclear palsy and in brains of mouse and fruit fly models of tauopathy.

"We found substantial deposits of double-stranded RNA in astrocytes, which are cells that provide metabolic support for neurons, regulate neurotransmitters and maintain blood-brain barrier integrity," Frost said. "In aging and disease, astrocytes respond to injury and disruption of the neuronal environment. Our findings open new doors for understanding astrocyte biology and their role in transposable element control."

Loss of neurons, which are cells of the central nervous system, is progressive in Alzheimer's and other neurodegenerative diseases.

The researchers conducted experiments in fruit flies to quickly test their questions about double-stranded RNA and inflammation in the brain. "To ensure that what we found in our fruit fly experiments is relevant to mammalian disease, we also studied brain tissue from mouse models and from postmortem human brains affected by tauopathy," Ochoa said.

"As we are currently targeting jumping gene activation in a local Phase II clinical trial for patients with Alzheimer's disease, it's important to understand the full repertoire of toxic molecules, including double-stranded RNAs, that jumping genes produce," Frost said.

Ochoa recently earned her Ph.D. from the Cell Biology, Genetics and Molecular Medicine Discipline of the Integrated Biomedical Sciences program at UT Health San Antonio. She earned her undergraduate degree from Seattle University.

Frost, associate professor of cell systems and anatomy in the Barshop and Biggs institutes at UT Health San Antonio, received the highly competitive Edith and Peter O'Donnell Award in Medicine in 2020 from TAMEST, the Texas Academy of Medicine, Engineering, Science and Technology. She was also a Gold Medalist in 2022 for the prestigious Oskar Fischer Prize.

More information: Elizabeth Ochoa et al, Pathogenic tau–induced transposable element–derived dsRNA drives neuroinflammation, Science Advances (2023). DOI: 10.1126/sciadv.abq5423

https://medicalxpress.com/news/2023-01-inflammatory-trigger-clue-alzheimer.html

CureVac's 'half-baked' COVID-flu data release questioned

 CureVac and GSK have picked the mRNA approach that will advance in the clinic for flu and COVID-19 after seeing phase 1 data on a handful of candidates. While analysts were happy to see the win, they were skeptical of the lack of updated variant data and limited population read-out—even going so far as to call the disclosure “half-baked.”

Germany-based CureVac said Friday that preliminary data from the early-stage trials for its COVID-19 and seasonal flu shots look good. The vaccines, which use CureVac’s second-generation mRNA backbone, produced an immune response and were generally well tolerated with no safety concerns.

The small disclosure boosted CureVac’s shares by 17% to $7.49 Friday morning, despite a data release that seemed to leave more questions than answers during a conference call Friday morning. 

The companies were testing a selection of potential vaccines featuring modified and unmodified mRNA. The COVID program had two monovalent candidates, while the flu tests included an unmodified multivalent and a modified monovalent vaccine candidate. CureVac shared data on the modified, monovalent mRNA COVID-19 vaccine called CV0501 and the modified mRNA flu candidate named Flu-SV-mRNA.

CV0501 was tested in 30 subjects and produced neutralizing titers against the omicron variant BA.1 beginning at the lowest tested dose. The data available are only for the younger adult group, ages 18-64, while more information on the older demographic is forthcoming. The shot was generally well tolerated.

Flu-SV-mRNA was trialed against an unnamed licensed seasonal flu vaccine and showed antibody titers 3.3 times that of the comparator in younger adults. The shot was also well tolerated, according to the release. Data for older adults are pending.

But even without those pieces, GSK and CureVac have what they need to move forward with the modified vaccines this year. While CV0501 was assessed against omicron variant BA.1, the upcoming phase 2 study will feature monovalent and/or bivalent vaccine candidates that go after clinically relevant variants, according to CureVac. As for the flu shot, CureVac said the future clinical candidate will go after all four World Health Organization-recommended strains. A phase 1/2 trial will begin in mid-2023.

Analysts congratulated CureVac on the data during the conference call but had hoped to see a more robust read-out than what was presented Friday. They had plenty of questions about what was missing, including the older adult population, current variant data, a comparison to Moderna, a combination flu/COVID strategy and a firm timeline for phase 3 advancement.

One analyst asked CureVac CEO Franz-Werner Haas and interim Chief Development Officer Ulrike Gnad-Vogt why they didn’t wait until they had more to share, calling the omission of the older population “half-baked.” Haas defended the news release, saying that the idea was to show the platform is working after the company’s first generation COVID candidate failed in 2021.

“What we … have been showing you today is telling you something about the functioning and the workings of our mRNA technology, not that much with regards to what are the next steps in product development, which will come soon,” Haas promised. The limited data are meant to show that the platform has overcome the limitations seen in the first shot.

CureVac’s mRNA platform uses optimized mRNA to carry data to instruct the body to fight disease. Haas said in the company’s statement that the results validate the company’s cancer portfolio as well, since it uses the same tech.

Haas said “it’s a bit too early to say” whether a combination flu-COVID shot will be commercially viable, although mRNA platforms are able to respond to the latest variants quickly to allow new versions to be manufactured. This has been evidenced by CureVac’s peers, Moderna and BioNTech-Pfizer, which have released updated bivalent COVID shots for the 2022/2023 season.

The small Friday release included the BA.1 variant, whereas the Centers for Disease Control and Prevention is tracking BA.2, BA.4 and BA.5 at the moment. Gnad-Vogt said the BA.4 and BA.5 strains will be included in the upcoming trials, which will put the candidates up against a currently approved shot.

“Certainly, you can see that this is exactly where RNA is so interesting for these kinds of developments, is there are new strains, and then we will all see how this epidemiology will develop and what the next clinical trials will be,” Haas said.

Another analyst wanted to know how CV0501 stands up to Moderna’s offering, but the executives didn't bite. Haas explained that, while a comparison could be made with publicly available data on Moderna’s shot, the comparison would not be scientifically accurate because the two products were not tested against each other in the same study. That kind of test will come later, he promised.

The executives were peppered with questions about the timing of a potential phase 3 but didn’t have much to share beyond saying they need to analyze full data from the studies presented today before they can make a decision. A dose has not yet been selected for the next phase of clinical development.

The GSK partnership was signed in July 2020 in the height of the pandemic, but so far has notched a failure and a re-do. With the next-generation attempt now showing some fruit, Haas said conversations with GSK are happening around the future of the partnership and whether any other targets will be advanced.

“It is exciting to see these data, especially in contrast to what we've been seeing on the earlier construct—and this motivates, I can tell you,” the CEO said.

In the company’s earlier statement, Haas said CureVac will “enter 2023 as a competitive player in the development of mRNA therapies.”

https://www.fiercebiotech.com/biotech/curevacs-half-baked-covid-flu-data-release-questioned-analysts-shares-still-rally-17

EPA tightens soot standards for first time in decade

 The U.S. Environmental Protection Agency will tighten national air quality standards for fine particle pollution emitted from vehicles and industrial sources for the first time since 2012, the agency said on Friday.

Fine particulate matter, or soot, comes from sources ranging from power plants to cars and trucks and refineries. It causes lung and heart damage and has been found to disproportionately affect low-income communities, according to the EPA.

"Fine particulate matter is both deadly and extremely costly," EPA Administrator Michael Regan told reporters, adding the decision was based on science and a rigorous evaluation of available data.

The proposal would lower the allowable concentration of particulate matter smaller than 2.5 microns, or PM 2.5, to a range of 9 to 10 micrograms per cubic meter (µg/m3) on average per year, from the current 12 µg/m3 in place since 2012. The EPA said it would also take public comment on revising the level to as low as 8 µg/m3, and as high as 11 µg/m3.

Public health and environmental groups on Friday welcomed the decision but criticized the agency for not going further.

Most members of the EPA's Clean Air Scientific Advisory Committee (CASAC) had recommended that the annual average start in a range as low as 8-10 µg/m3 and the primary 24-hour PM 2.5 standard be lowered to 25 µg/m3. EPA left the 24-hour standard intact at 35 µg/m3.

A study that the Environmental Defense Fund commissioned found that an annual standard of 8 µg/m3 prevents more than four times as many premature deaths as a standard of 10 µg/m3.

"The science is clear that we need standards at the most protective ends of the ranges that EPA's own scientific advisors recommended," said National Assistant Vice President at the American Lung Association Laura Kate Bender, who said dozens of groups will press for tighter standards during the 60-day public comment period.

The EPA evaluates the PM2.5 standard every five years and tends to tighten the level after review. It will finalize the rule later this year after it reviews public comments.

Former President Donald Trump's administration had kept the 2012 standard despite mounting research that those levels threaten public health.

The EPA estimates that an annual PM2.5 standard of 9 µg/m3 would prevent up to 4,200 premature deaths per year and yield $43 billion in net health benefits in 2032.

Groups representing the cement, manufacturing and oil industries criticized the rule for adding regulatory burdens and said some companies may not be able to comply.

"The proposed tightening of PM NAAQS will likely result in PM emissions standards being technically and economically infeasible for the industry to meet," said Mike Ireland, president of the Portland Cement Association.

Meanwhile, Earthjustice, which had sued the EPA to update the PM2.5 standard left by the Trump administration, said Friday's proposal was a "missed opportunity" to address daily spikes in soot pollution that affect some 63 million people in the United States.

"EPA is not living up to the ambitions of this administration to follow the science, protect public health, and advance environmental justice,” said Seth Johnson, Earthjustice attorney.

https://www.yahoo.com/news/u-epa-tightens-soot-standards-151400819.html

Who can get the newly approved Eisai and Biogen Alzheimer's drug?

 The U.S. Food and Drug Administration on Friday approved Eisai Co Ltd and Biogen Inc's Alzheimer's drug lecanemab for the treatment of early forms of the fatal, brain-wasting disease.

Like their earlier Alzheimer's drug Aduhelm, lecanemab, to be sold under the brand name Leqembi, belongs to a class of treatments that aim to slow disease progression by removing sticky clumps of the toxic protein beta amyloid from the brain.

Here's what we know about access to the drug so far:

PATIENT POPULATION

Leqembi was approved for patients with Alzheimer's disease, and is recommended for use in people with mild cognitive impairment or early Alzheimer's - the same population in which the drug was tested.

To qualify for treatment, patients will need to have a special diagnostic test - either a PET scan of the brain or spinal tap - to confirm the presence of amyloid in the brain.

MEDICARE COVERAGE

The companies said the drug would be available to patients during or before the week of Jan. 23. However, most patients will have to pay out of pocket for the drug, which costs $26,500 a year, as insurance coverage will be limited.

The U.S. Centers for Medicare & Medicaid Services (CMS) said Leqembi falls under its current policy severely limiting coverage of amyloid-lowering drugs to people enrolled in an approved clinical trial if the drug has gone through the FDA's accelerated approval process.

CMS, which runs the national Medicare healthcare plan for those age 65 and older, said in a statement it is currently reviewing all available data and "may reconsider" its coverage decision. The agency added that it would provide broader coverage if the drug receives standard FDA approval. The companies said they intend to apply for full approval shortly.

"Given the data behind lecanemab, there is a case that Eisai can make for CMS reimbursement for the drug," said BMO analyst Evan Seigerman, adding that the drugmaker will need to negotiate with the agency.

SAFETY

The drug comes with a requirement that patients undergo four MRI scans over the course of 14 weeks to check for signs of Amyloid Related Imaging Abnormalities or “ARIA," a type of temporary brain swelling that is frequently seen with drugs that remove amyloid from the brain.

In some patients, this type of brain swelling has led to hemorrhages. Because of that, Leqembi's label urges doctors to warn patients of this risk, especially if patients are already taking blood thinners.

The label urges doctors to be especially careful in giving the clot-busting stroke treatment known as a tissue plasminogen activator, or t-PA, to patients taking Leqembi, saying it can increase the risk of bleeding in the brain.

Because of this risk, some physicians have said they would not recommend Leqembi for patients on blood thinners.

https://www.yahoo.com/news/factbox-newly-approved-eisai-biogen-223915881.html

Russian hackers targeted U.S. nuclear scientists

 A Russian hacking team known as Cold River targeted three nuclear research laboratories in the United States this past summer, according to internet records reviewed by Reuters and five cyber security experts.

Between August and September, as President Vladimir Putin indicated Russia would be willing to use nuclear weapons to defend its territory, Cold River targeted the Brookhaven (BNL), Argonne (ANL) and Lawrence Livermore National Laboratories (LLNL), according to internet records that showed the hackers creating fake login pages for each institution and emailing nuclear scientists in a bid to make them reveal their passwords.

Reuters was unable to determine why the labs were targeted or if any attempted intrusion was successful. A BNL spokesperson declined to comment. LLNL did not respond to a request for comment. An ANL spokesperson referred questions to the U.S. Department of Energy, which declined to comment.

Cold River has escalated its hacking campaign against Kyiv's allies since the invasion of Ukraine, according to cybersecurity researchers and western government officials. The digital blitz against the U.S. labs occurred as U.N. experts entered Russian-controlled Ukrainian territory to inspect Europe's biggest atomic power plant and assess the risk of what both sides said could be a devastating radiation disaster amid heavy shelling nearby.

Cold River, which first appeared on the radar of intelligence professionals after targeting Britain's foreign office in 2016, has been involved in dozens of other high-profile hacking incidents in recent years, according to interviews with nine cybersecurity firms. Reuters traced email accounts used in its hacking operations between 2015 and 2020 to an IT worker in the Russian city of Syktyvkar.

"This is one of the most important hacking groups you’ve never heard of," said Adam Meyers, senior vice president of intelligence at U.S. cybersecurity firm CrowdStrike. "They are involved in directly supporting Kremlin information operations."

Russia's Federal Security Service (FSB), the domestic security agency that also conducts espionage campaigns for Moscow, and Russia's embassy in Washington did not respond to emailed requests for comment.

Western officials say the Russian government is a global leader in hacking and uses cyber-espionage to spy on foreign governments and industries to seek a competitive advantage. However, Moscow has consistently denied that it carries out hacking operations.

Reuters showed its findings to five industry experts who confirmed the involvement of Cold River in the attempted nuclear labs hacks, based on shared digital fingerprints that researchers have historically tied to the group.

The U.S. National Security Agency (NSA) declined to comment on Cold River's activities. Britain's Global Communications Headquarters (GCHQ), its NSA equivalent, did not comment. The foreign office declined to comment.

'INTELLIGENCE COLLECTION'

In May, Cold River broke into and leaked emails belonging to the former head of Britain's MI6 spy service. That was just one of several 'hack and leak' operations last year by Russia-linked hackers in which confidential communications were made public in Britain, Poland and Latvia, according to cybersecurity experts and Eastern European security officials.

In another recent espionage operation targeting critics of Moscow, Cold River registered domain names designed to imitate at least three European NGOs investigating war crimes, according to French cybersecurity firm SEKOIA.IO.

The NGO-related hacking attempts occurred just before and after the October 18 launch of a report by a U.N. independent commission of enquiry that found Russian forces were responsible for the "vast majority" of human rights violations in the early weeks of the Ukraine war, which Russia has called a special military operation.

In a blog post, SEKOIA.IO said that, based on its targeting of the NGOs, Cold River was seeking to contribute to "Russian intelligence collection about identified war crime-related evidence and/or international justice procedures." Reuters was unable independently to confirm why Cold River targeted the NGOs.

The Commission for International Justice and Accountability (CIJA), a nonprofit founded by a veteran war crimes investigator, said it had been repeatedly targeted by Russian-backed hackers in the past eight years without success. The other two NGOs, the International Center of Nonviolent Conflict and the Centre for Humanitarian Dialogue, did not respond to requests for comment.

Russia's embassy in Washington did not return a request seeking comment about the attempted hack against CIJA.

Cold River has employed tactics such as tricking people into entering their usernames and passwords on fake websites to gain access to their computer systems, security researchers told Reuters. To do this, Cold River has used a variety of email accounts to register domain names such as "goo-link[.]online" and "online365-office[.]com" which at a glance look similar to legitimate services operated by firms like Google and Microsoft, the security researchers said.

DEEP TIES TO RUSSIA 

Cold River made several missteps in recent years that allowed cybersecurity analysts to pinpoint the exact location and identity of one of its members, providing the clearest indication yet of the group's Russian origin, according to experts from Internet giant Google, British defense contractor BAE, and U.S. intelligence firm Nisos.

Multiple personal email addresses used to set up Cold River missions belong to Andrey Korinets, a 35-year-old IT worker and bodybuilder in Syktyvkar, about 1,600 km (1,000 miles) northeast of Moscow. Usage of these accounts left a trail of digital evidence from different hacks back to Korinets' online life, including social media accounts and personal websites.

Billy Leonard, a Security Engineer on Google's Threat Analysis Group who investigates nation state hacking, said Korinets was involved. "Google has tied this individual to the Russian hacking group Cold River and their early operations," he said.

Vincas Ciziunas, a security researcher at Nisos who also connected Korinets' email addresses to Cold River activity, said the IT worker appeared to be a "central figure" in the Syktyvkar hacking community, historically. Ciziunas discovered a series of Russian language internet forums, including an eZine, where Korinets had discussed hacking, and shared those posts with Reuters.

Korinets confirmed that he owned the relevant email accounts in an interview with Reuters but he denied any knowledge of Cold River. He said his only experience with hacking came years ago when he was fined by a Russian court over a computer crime committed during a business dispute with a former customer.

Reuters was able separately to confirm Korinets' links to Cold River by using data compiled through cybersecurity research platforms Constella Intelligence and DomainTools, which help identify the owners of websites: the data showed that Korinets' email addresses registered numerous websites used in Cold River hacking campaigns between 2015 and 2020.

It is unclear whether Korinets has been involved in hacking operations since 2020. He offered no explanation of why these email addresses were used and did not respond to further phone calls and emailed questions.

https://www.yahoo.com/news/exclusive-russian-hackers-targeted-u-144728635.html