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A University of Houston researcher is working to increase health literacy among Hispanics/Latinos (H/Ls) when it comes to Alzheimer's disease (AD). The largest ethnic minority in the U.S., at 18% of the population, H/Ls are 50% more likely to develop Alzheimer's disease than non-Hispanic whites. H/Ls also live longer, develop AD symptoms earlier, are diagnosed at later stages and are less likely to be treated.

Given those statistics, it's startling that Hispanics/Latinos comprise less than 1% of clinical trials for Alzheimer's disease.

"From a social justice perspective, in order to help reduce health disparities we need to involve these communities in the decision-making process," said Luis D. Medina, assistant professor of psychology. He will use a $2.35 million grant from the National Institute on Aging to build his "Engaging Communities of Hispanics for Aging Research Network."

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"There are various barriers to getting involved in research, including health literacy or what people actually know about Alzheimer's disease. In the Hispanic/Latino communities, it is often thought of as just a part of aging," said Medina, who believes the solution begins with education.

The network will launch in two pilot cities, Houston and Denver. Step one is "boot camp translation" wherein community stakeholders are immersed in learning about the disease, and then the tables turn – the community members educate the trainers on how to speak to their communities.

In boot camp translation we break down the medical jargon to consumable, understandable lay language and the community tells us how to do that. The communities have a lot of strengths that we, as researchers, may or may not have. We are hoping to put more seats at the table so that the communities are involved in research infrastructure and help drive research projects."

Luis D. Medina, assistant professor of psychology, University of Houston

Steven Woods, UH professor of psychology and Jennifer Vardeman, UH associate professor of communication, are assisting on the project in collaboration with Baylor College of Medicine, University of Colorado School of Medicine, University of Nevada, Las Vegas and the Lou Ruvo Center for Brain Health at the Cleveland Clinic in Las Vegas.

Medina plans to expand the project to Las Vegas next as he creates a template for other cities to follow.

"This is about lifting all of us up and improving brain health. The more representative our research samples are, the better we can understand the disease," said Medina, who was recently invited to serve on the Alzheimer's Association International Research Grant Program Council to help craft funding opportunity requests for applications, provide expertise during grant review and make funding recommendations. The association is especially interested in Medina's input on issues related to the recruitment of underrepresented populations.

Source:

University of Houston

After 50 years of research and the testing of over 1,000 drugs, there is new hope for preserving brain cells for a time after stroke. Treating acute ischemic stroke patients with an experimental neuroprotective drug, combined with a surgical procedure to remove the clot improves outcomes as shown by clinical trial results published today in The Lancet.

The multi-center, double-blinded, randomized trial, led by a team at the Cumming School of Medicine's (CSM) Hotchkiss Brain Institute and Alberta Health Services, investigates the use of the neuroprotective drug nerinetide, developed by NoNO Inc, in two scenarios in the same trial. In one scenario, nerinetide is given to patients in addition to the clot-busting drug alteplase. In the second scenario, patients who were not suitable for alteplase received only nerinetide. Both groups of patients had concurrent endovascular treatment (EVT) to remove the clot.

"Compared to placebo, almost 20 per cent more patients who received nerinetide along with endovascular treatment, but did not receive alteplase, recovered from a devastating stroke – a difference between paralysis and walking out of the hospital," says Dr. Michael Hill, MD, a neurologist at Foothills Medical Centre (FMC) and professor in the departments of Clinical Neurosciences and Radiology at the CSM. "In the patients who received both drugs, the alteplase negated the benefits of the nerinetide."

Hill says the study provides evidence of a biological pathway that protects brain cells from dying when they are deprived of blood flow. Nerinetide targets the final stage of the brain cell's life by stopping the production of nitric oxide within the cell.

"We really believe this is a new scientific observation," says Hill. "There is evidence nerinetide promotes brain cell survival, offering neuroprotection until we can extract the clot. It opens the door to a new way of treating stroke."

Images of patients' brains from the study show the expected size of the damage from the stroke is sizeably reduced when nerinetide is administered and EVT is performed among patients not concurrently receiving alteplase.

After so many studies investigating neuroprotective drugs failed, we are extremely excited by these results. While nerinetide is not approved for use yet, it shows the potential of a new tool to promote recovery from stroke."

Dr. Mayank Goyal, MD, PhD, neuroradiologist at the FMC, and clinical professor in the Department of Radiology at the CSM

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Worldwide, 15 million people suffer a stroke each year – that's one every nine minutes in Canada and every 90 seconds in the United States. The results can be devastating. Ischemic stroke, the most common, is caused by a clot in a blood vessel in the brain. The sudden loss of blood flow causes brain cells to die, which can permanently affect speech, vision, balance and movement.

The international trial enrolled 1,105 patients between March 2017 and August 2019 at centres in North America, Europe, Australia, and Asia – a global academic collaboration bringing together scientists, clinicians, funding agencies, and industry.

"The collaboration between NoNO Inc., the University of Calgary and investigators at 48 leading stroke hospitals around the world has shown how effective such an academic-industry partnership can be in running high-quality, foundational stroke trials that can lead to positive changes in clinical practice," says Dr. Michael Tymianski, MD, PhD, CEO of NoNO Inc. and the inventor of nerinetide.

The results in the current study, called the ESCAPE-NA1 Trial, build on the success of the ESCAPE trial, in which the Calgary Stroke Program proved that a clot retrieval procedure known as EVT can dramatically improve patient outcomes after an acute ischemic stroke. During the procedure, a catheter is inserted in the groin and guided through blood vessels into the brain. A tiny metal mesh device is used to grab the clot and pull it out. The current study investigates whether administering nerinetide in addition to clot retrieval improves the patient's ability to recover.

Source:

University of Calgary

Journal reference:

Hill, M.D, et al. (2020) Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial. The Lancet. doi.org/10.1016/S0140-6736(20)30258-0.

Mount Sinai Researchers find social isolation during key developmental windows drives long term changes to activity patterns of neurons involved in initiating social approach in an animal model.

Corresponding Author: Hirofumi Morishita, MDPhD, together with Schahram Akbarian MDPhD Icahn School of Medicine at Mount Sinai, New York, and other coauthors (first author Lucy Bicks).

Bottom Line: Loneliness is increasingly being recognized as a serious threat to mental health and wellbeing in our society. Our study in an animal model shows that social isolation during adolescence leads to long-term disruptions in social behavior and disruptions to activity patterns of a type of inhibitory neuron in the brain, which are frequently disrupted in psychiatric disorders including Schizophrenia. Activity patterns of these inhibitory neurons are sufficient to rescue social deficits induced by juvenile social isolation.

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Results: Social behavior is composed of interactions where mice are actively exploring conspecifics or passively being explored. We find one population of neurons, parvalbumin expressing inhibitory neurons, increases in activity prior to an active, but not a passive social interaction. Brief activity of these neurons is sufficient to promote increased active social behavior. Juvenile social isolation during adolescence disrupts the activity of these neurons, leading to a decoupling of their activity and subsequent active social behavior initiation. Increasing activity of these neurons in adult animals that were socially isolated during adolescence restores normal social behavior.

Why the Research Is Interesting: The findings help us to understand how social experience during key windows of development might shape long term behavioral outcomes through changes to specific circuits in the brain. Understanding how social experience shapes outcomes can help us to overcome social deficits in cases of early life trauma or in neurodevelopmental and psychiatric disorders with social deficits.

Who: Mouse models deprived of social experience during the juvenile period.

When: Mice were deprived of social experience during a juvenile phase and their behavior and physiology were examined in adulthood.

What: The study measured activity of parvalbumin expressing inhibitory neurons during social interaction as well as input drive to these neurons.

How: We measured parvalbumin expressing inhibitory neuron activity during social behavior and manipulated activity of these neurons using advanced technologies.

Study Conclusions: Social experience early in life alters specific patterns of parvalbumin expressing inhibitory neurons in prefrontal cortex. This pattern of activity is essential for active social approach behavior in mice.

Paper Title: Prefrontal parvalbumin interneurons require juvenile social experience to establish adult social behavior.

Source:

The Mount Sinai Hospital / Mount Sinai School of Medicine

Journal reference:

Bicks, L.K., et al. (2020) Prefrontal parvalbumin interneurons require juvenile social experience to establish adult social behavior. Nature Communications. doi.org/10.1038/s41467-020-14740-z.

When you're facing a cancer diagnosis with an average survival span of 12 to 18 months, every milestone is a victory. That makes each wedding invitation, graduation announcement and birthday photo that UCI neuro-oncologist Dr. Daniela Bota receives from her patients a cherished validation of her 12 years of groundbreaking research on glioblastoma multiforme, the most aggressive form of brain cancer. "Because of our work, these people have been able to move on with their lives," she says.

Bota has pushed the boundaries of innovation in her quest to increase the survival rates of individuals with brain tumors, especially glioblastomas. The esteemed physician-scientist has taken a truly comprehensive approach to battling this rare disease, which has a five year survival rate of only 10 percent and claimed the lives of U.S. Sens. Ted Kennedy and John McCain. Bota has conducted clinical trials of multiple cutting-edge treatments that are improving the quantity as well as the quality of life for glioblastoma patients at UCI and beyond.

'So much potential, so much growth'

Bota grew up in Romania, in a family of engineers. It was assumed she'd follow them into the profession – she was a national mathematics champion in her youth – but Bota had another path in mind. "I wanted to make a more significant contribution," she says. "I wanted to combine my analytical side with a place where I could help others. I ended up becoming an M.D.-Ph.D. to blend both."

At USC, Bota earned a doctorate in molecular biology, focusing on neural degeneration. She then went to the University of Kansas for medical school and a residency in neurology. During her shifts, Bota found herself caring for people with brain tumors – and discovered a new direction for her medical career.

The generosity and gratitude of brain tumor patients make it so rewarding to care for them. I see it again and again at UCI. Many of these patients have a terminal diagnosis, but they're volunteering their time and energy to participate in our clinical trials to help us build a better treatment and, hopefully, in the future, a cure."

Dr. Daniela Bota, UCI neuro-oncologist

After a neuro-oncology fellowship at Duke University, Bota joined the faculty of UCI's School of Medicine and the Chao Family Comprehensive Cancer Center in November 2007. "Both my career and UCI in general have grown so tremendously over the dozen years since," says Bota, who's now co-director of the UCI Health Comprehensive Brain Tumor Program. "There has been so much potential, so much growth, so many changes and so much scientific revolution helping us move forward in so many different directions. It's a very exciting time."

A comprehensive approach

The word "comprehensive" carries significant weight in the realm of cancer care centers. The "comprehensive" designation from the National Cancer Institute recognizes an added depth and breadth of research that bridges multiple scientific areas. Just 51 cancer centers in the U.S. carry the designation; the Chao Family Comprehensive Cancer Center is the only one in Orange County. "We offer one of the most innovative and complex portfolios of clinical trials anywhere in the world," Bota says.

Her own multipronged attack against glioblastoma multiforme reflects the center's comprehensive approach. Bota's work on the experimental drug marizomib has generated significant attention and hope. Unlike traditional chemotherapy drugs, marizomib can penetrate the blood-brain barrier – the filtering mechanism that prevents many blood-borne substances from passing into brain tissues – and inhibit cancer growth without causing damage to other parts of the brain.

Over the past 12 years, Bota has shepherded marizomib from preclinical development all the way through a 700-person international phase III clinical trial now underway. "We have a number of patients from our clinical trials who are surviving this tumor for longer periods of time than usually expected," she says.

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Amanda Johnson, a 32-year-old freelance writer in Mission Viejo, has been receiving marizomib for two years under Bota's care. Her large glioblastoma tumor – which straddled both sides of her brain – has shrunk so much that it's no longer measurable. She has returned to work on her novel and even joined a gym. "I feel so happy just to be alive," Johnson says.

Larry Johnson, her father, told Fox News, "I don't think [Amanda] has come to realize how important her survival is to other people and families who are going to find themselves in a similar situation."

Bota strives to reach a point where such cases will be so commonplace that they don't make the news. "That's what success looks like – not having a prominent publication or being part of a game-changing discovery," she says. "It's having patients like Amanda still be here and doing well."

Vaccine trials and right to try

To achieve that goal, Bota tenaciously pursues multiple avenues of treatment. She has been a leader in the use of Optune, a device worn on the head that generates an electrical field that disrupts the growth of cancer cells. "We were among the first in the country to explore and use this technology," Bota says. "Now we're working with physicians from other countries to help them adopt it in their practices."

She is also spearheading two clinical trials on cancer vaccines. "Brain tumors hide behind the blood-brain barrier, so the body doesn't recognize them as not being a normal part of the body," Bota explains. "With our vaccines, we extract cellular markers from the patient's tumor and inject them back into the patient to stimulate the immune system to recognize those tumors, attack them and, if possible, eliminate them."

She adds: "Both studies have been well-received in our neuro-oncological community, which is highly promising. And a significant benefit is that the vaccines function with minimal or no toxicity."

In January 2019, one of Bota's patients who was ineligible for both clinical trials was able to access one of the vaccines through the first successful application of the national Right to Try Act. Passed in May 2018, it allows people with terminal illnesses, in consultation with their doctors, to seek treatment with experimental drugs not yet approved by the Food and Drug Administration directly from pharmaceutical companies. "The law puts patients in charge of their care; they initiate contact with the manufacturer and request therapy," Bota says. "It gives patients who don't qualify for clinical trials another option."

"We offer one of the most innovative and complex portfolios of clinical trials anywhere in the world."

Sharing her expertise

Bota eagerly offers her knowledge beyond the doors of the Chao Family Comprehensive Cancer Center. Whenever she and her husband, Robert, a local psychiatrist, travel back to their home country of Romania, she consults with medical colleagues there, as there are no certified neuro-oncologists in the nation. On days when the couple work on their farm in the Transylvanian Alps, locals come to them – often on foot – for medical advice. The two hope to eventually establish a clinic in the area. "I want to make sure that Romania also benefits from my medical expertise," Bota says.

Back on campus, in her capacity as senior associate dean for clinical research, she uses her vast clinical trial experience to help colleagues in UCI's School of Medicine advance their own research projects into the clinical arena.

"I'm excited by the ability to impact the lives of so many people through this role," Bota says. "Whether it's for burns or vascular disorders or other conditions, people come to UCI for the same reason: We can offer what community hospitals cannot. Being able to make that happen, to create new options for our patients, is what wakes me up in the morning."

Source:

University of California, Irvine

Using cutting-edge imaging technology, researchers at Massachusetts General Hospital (MGH) have shown that the brains of young men with autism spectrum disorder (ASD) have low levels of a protein that appears to play a role in inflammation and metabolism. This surprising discovery, which published online today in the journal Molecular Psychiatry provides an important new insight into the possible origins of ASD, which affects one in 59 children.

ASD is a developmental disorder that emerges in early childhood and is characterized by difficulty communicating and interacting with others. While the cause is unknown, growing evidence has linked ASD to inflammation of brain tissue, or neuroinflammation. One sign of neuroinflammation is elevated levels of a substance called translocator protein (TSPO), which can be measured and located in the brain using positron-emission tomography (PET) and anatomical magnetic resonance imaging (MRI). The MGH study, led by Nicole Zurcher, PhD, an investigator in MGH's Athinoula A. Martinos Center for Biomedical Imaging, was the first to use a new generation of PET "tracers," which more accurately detect TSPO, to examine the brains of people with ASD.

In the study, Zurcher and her colleagues scanned the brains of 15 young adult males (average age, 24) with ASD. The group included both high- and low-functioning subjects with varying degrees of intellectual abilities. For comparison, Zurcher's team scanned the brains of 18 healthy control subjects who were similar in age. The investigators hypothesized that the scans would show increased levels, or expression, of TSPO in subjects who have ASD.

"To our surprise, that's not what we saw," says Zurcher. Instead, the scans showed that the brains of males with ASD had lower levels of TSPO than those of the healthy subjects. In fact, the men with the most severe symptoms of ASD tended to have the lowest expression of TSPO. When the tests were repeated several months later, the pattern persisted. The brain regions found to have low expression of TSPO have previously been linked to ASD in earlier studies, and are believed to govern social and cognitive capacities such as processing of emotions, interpreting facial expressions, empathy, and relating to others. "We know these brain regions are involved in autism," says Zurcher.

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To understand this unexpected finding, Zurcher notes that TSPO does more than serve as a marker of inflammation. "It has multiple complex roles," she says, and some actually promote brain health. For example, adequate TSPO is necessary for normal functioning of mitochondria, which are the "power houses" in cells that produce energy. Earlier research has linked malfunctioning mitochondria in brain cells to ASD.

Zurcher and her colleagues next plan to study brains from deceased donors with the goal of determining which brain cells in people with ASD might experience mitochondrial dysfunction, which she says may well be occurring alongside neuroinflammation and other mechanisms to cause ASD.

Our study has generated new hypotheses that now need to be investigated. There's more work to be done."

Nicole Zurcher, PhD, investigator, MGH's Athinoula A. Martinos Center for Biomedical Imaging

Source:

Massachusetts General Hospital

Journal reference:

Zürcher, N.R., et al. (2020) [11C]PBR28 MR–PET imaging reveals lower regional brain expression of translocator protein (TSPO) in young adult males with autism spectrum disorder. Molecular Psychiatry. doi.org/10.1038/s41380-020-0682-z.

The coronavirus may have emerged from a Wuhan laboratory leak, which studies deadly pathogens such as the SARS virus, scientists suggest.

Health officials believe that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease (COVID-19), originated from wild animals sold in the Huanan Seafood Wholesale Market in Wuhan City, which is home to 11 million residents.

Now, a team of scientists from Xishuangbanna Tropical Botanical Garden of Chinese Academy of Sciences, South China Agricultural University, and Chinese Institute for Brain Research wrote in a paper published on ChinaXiv, about an alternative source of the coronavirus that is currently spreading across the globe.

The scientists say they have found genomic evidence that the seafood market is not the actual source of the outbreak. Instead, they point the source of the virus outbreak to a laboratory that studies potent viruses.

The Wuhan Virology Institute researches some of the world's most dangerous pathogens. It is China's first Biosafety Level 4 laboratory, the highest security level needed to isolate dangerous biological agents in an enclosed facility.

Image Credit: Connect World / Shutterstock

The spread of the virus

The scientists in the study speculated that the outbreak of the virus has started before December 2019, probably beginning in late November. Further, the busy seafood market may have facilitated the transmission of the virus to buyers, and from buyers to residents across the city.

In the study, the researchers collected genome-wide information from 93 new coronavirus samples shared on the GISAID EpiFlu, which is an international database storing information about the influenza virus. The team studied the evolution and human-to-human transmission of the coronavirus over the past two months.

The samples were taken from 12 countries, wherein 54 came from China before Jan. 22 and the other 39 samples were from France, Australia, Japan, and the United States after Jan. 22.

The team also found that while the virus had spread in the seafood market in Wuhan, there had also been two major population expansions, dated Dec. 8 and Jan. 6. Further, scientists believe that the virus originated outside the market, but the crowded market had boosted the circulation of the coronavirus, spreading it to the whole city by December 2019.

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The first case manifesting symptoms emerged on Dec. 8, and most of the following cases were linked to the seafood market. On Jan. 1, the seafood market was closed, but the virus had already spread in the city, suggesting that the outbreak has started through human-to-human transmission by late November.

Warning about the new virus

“The study concerning whether the Huanan market is the only birthplace of SARS-CoV-2 is of great significance for finding its source and determining the intermediate host to control the epidemic and prevent it from spreading again,” the researchers said.

The researchers also said that while at the beginning of the outbreak in Hubei province and neighboring areas, China’s National Center for Disease Control and Prevention issued a level 2 emergency warning about the new outbreak on Jan. 6, the information was not widely shared. The team said if warning received more attention, the number of cases in China, and across the globe would have been reduced.

The government has locked down Wuhan city on Jan. 23, which is weeks after the outbreak has been reported. Before the residents were barred from leaving the city in fear of spreading the virus, millions have already left.

The Wuhan Institute of Virology, which is the only laboratory in China that is equipped to study with such deadly infectious diseases, released a statement saying that the rumors had caused great harm to the researchers of the laboratory.

The origin of the new coronavirus is still unknown, but scientists and the World Health Organization (WHO) said it is most likely an animal reservoir.

Coronavirus by the numbers

The coronavirus disease (COVID-19) has already spread to 30 countries, with South Korea reporting the greatest number of infections after China. As of writing, there are 763 people in South Korea testing positive for the deadly virus.

The coronavirus has infected nearly 80,000 people, most of whom in mainland China and the death toll has reached 2,670, which is more than twice the number of deaths linked to SARS in 2003.

Countries across the globe, particularly those fearing the rapid spread of the virus, have imposed travel bans from countries who have confirmed cases of the coronavirus. Meanwhile, Italy has also reported a spike in cases, with 155 people testing positive while three patients have succumbed to the disease.

The World Health Organization (WHO) reported that no new countries had reported confirmed cases in the past 24 hours.

Sources:

  • Decoding evolution and transmissions of novel pneumonia coronavirus using the whole genomic data, Yu, Wen-Bin, Tang, Guang-Da, Zhang, Li, Corlett, Richard, http://www.chinaxiv.org/abs/202002.00033
  • World Health Organization (WHO). (2020). Coronavirus disease 2019 (COVID-19) Situation Report – 34. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200223-sitrep-34-covid-19.pdf?sfvrsn=44ff8fd3_2
  • http://www.ecns.cn/news/sci-tech/2020-02-23/detail-ifztvsqr0576579.shtml
  • https://www.globaltimes.cn/content/1180429.shtml
  • https://news.cgtn.com/news/2020-02-23/New-study-shows-Wuhan-seafood-market-not-the-source-of-COVID-19-OjhaHnwdnG/index.html

A new simple blood test for brain tumors that could be used by GPs in primary care is being developed thanks to funding of nearly £500,000 by Cancer Research UK. Around 60,000 patients in the UK are living with a brain tumor but only 20 per cent of patients are still alive five years after diagnosis, partly because they present late with large inoperable tumors.

The University of Bristol-led research project to develop an affordable, point of care blood test to diagnose brain tumors earlier using fluorescent carbon dots and nanophotonics will be headed by Dr. Kathreena Kurian, Associate Professor in Brain Tumour Research and Dr. Sabine Hauert, Senior Lecturer in Robotics in collaboration with co-investigators: Professors Carmen Galan and Richard Martin at the University of Bristol; Dr. Neciah Dorh at FluoretiQ Limited and Dr. Helen Bulbeck at Brainstrust.

The cross-disciplinary research project brings together medical practitioners, along with experts in population health, nanoparticle engineering and detection, as well as computational modeling.

Dr. Kathreena Kurian, Head of the Brain Tumour Research Centre at the University of Bristol, said:

A simple blood test carried out by GPs would help decision-making and early diagnosis. This would revolutionize care by speeding up diagnosis, reducing costs to the NHS, anxiety of unnecessary scans and reducing the number of patients presenting with inoperable large brain tumors.

Additionally, this test could be used as an early monitor of brain tumor recurrence. Our work will be followed by a multicentre cohort biomarker study to determine the effectiveness of the test in a real-world setting."

Dr. Sabine Hauert from the Department of Engineering Mathematics and Bristol Robotics Laboratory (BRL), added: "Nanoparticles have shown promise in early detection of cancer by fluorescent labeling of very low levels of biomarkers in blood samples and other fluids."

Dr. Alexis Webb, Cancer Research UK's senior early detection funding manager, said:

At the moment the number of people who survive after a brain tumor diagnosis remains low and little has changed in over a generation. We're proud to support this innovative project and funding brain tumor research remains a priority for the charity. We need better techniques to diagnose brain tumors earlier, when more treatment options are available, to secure a future for more people affected by the disease."

Professor Carmen Galan, Professor of Organic and Biological Chemistry in the School of Chemistry, who has developed the fluorescent carbon-based nanomaterials that form the basis for the project, explained: "The fluorescent nanoprobes are produced by low-cost renewable routes and we have shown that we can decorate them with different biomolecules to target specific biomarkers in physiological conditions, which is really exciting."

Dr. Neciah Dorh, CEO of FluoretiQ Limited, stated:

As a diagnostics company, we are passionate about creating technology that can improve people's lives and we see this project as natural extension of the work that we are currently doing in infectious disease."

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In the UK in 2013, 38 percent of brain tumor patients visited their GP five times or more before being referred for diagnosis by imaging MRI/CT scan and neurosurgical biopsy, because the symptoms such as headache are non-specific, so there is an urgent need to develop new tests for brain tumors to help GPs diagnose brain tumors earlier.

There is a pressing need for the discovery of new blood biomarkers for brain cancer and state-of-the-art technology that allows for its sensitive detection. The aims of the research project are:

  • discover novel biomarkers, in addition to known markers such as Glial fibrillary acidic protein (GFAP), which will be used as a baseline;
  • implement a computational model to predict biomarker levels in blood;
  • develop a fluorescent nanoparticle that can label this marker in blood;
  • work with Bristol-based start-up FluoretiQ towards an affordable near patient testing solution.

Glioblastoma is the most common type of malignant brain tumor among adults and it is usually very aggressive, which means it can grow fast and spread quickly. It is characterized by abnormal blood vessels following a leaky blood-brain barrier (BBB). GFAP is unique to the brain and not present in blood that circulates throughout the body. Antibodies in GFAP are used to diagnose gliomas in tissue samples. There is evidence that GFAP crosses the leaky BBB and is an early non-specific peripheral blood biomarker which predates the clinical diagnosis of glioblastoma.

However, GFAP levels are too low for routine detection by routine protein detection tests such as ELISA. The research team has already identified other novel potential protein biomarkers of brain tumours using the epidemiological method, Mendelian Randomization, which may be present in low levels in the blood.

Fluorescent carbon dots (FCDs), also known as nanoparticles, are cheap and easy to create using a three-minute synthesis. FCDs can be readily attached to ligands such as antibodies targeting specific protein markers. FCDs labeling biomarkers can then be detected using nanophotonic technology, which has been developed by FluoretiQ, for rapid, sensitive, and low-cost diagnosis. Computational modeling will then be used to predict tumor size given biomarker availability in blood and establish the theoretical limits of the detection.

Source:

University of Bristol

The addition of dietary L-serine, a naturally occurring amino acid necessary for formation of proteins and nerve cells, delayed signs of amyotrophic lateral sclerosis (ALS) in an animal study.

The research also represents a significant advance in animal modeling of ALS, a debilitating neurodegenerative disease, said David A. Davis, Ph.D., lead author and research assistant professor of neurology and associate director of the Brain Endowment Bank at the University of Miami Miller School of Medicine.

The new research protocol using vervets appears more analogous to how ALS develops in humans, Dr. Davis said, compared to historic models using rodents. When he and colleagues gave the vervets a toxin produced by blue-green algae known as β-N-methylamino-L-alanine or BMAA, they developed pathology that closely resembles how ALS affects the spinal cords in humans.

When a group of these animals were fed L-serine together with BMAA for 140 days, the strategy was protective – the vervets showed significantly reduced signs of protein inclusions in spinal cord neurons and a decrease in pro-inflammatory microglia. The results were published on Thursday, February 20 at 5 a.m. EST in the prestigious Journal of Neuropathology & Experimental Neurology.

"The big message is that dietary exposure to this cyanobacterial toxin triggers ALS-type pathology, and if you include L-serine in the diet, it could slow the progression of these pathological changes," Dr. Davis said.

"I was surprised at how close the model mirrored ALS in humans," he added. Beyond looking at changes in the brain, "When we looked at the spinal cord, that was really surprising." The investigators observed changes specific to ALS seen in patients, including presence of intracellular occlusion such as TDP-43 and other protein aggregates.

Walter G. Bradley D.M., F.R.C.P., founder of the ALS Clinical and Research Center at the University of Miami Miller School of Medicine, said: "ALS is a progressive neurological disease, also known as Lou Gehrig's disease, causing progressive limb paralysis and respiratory failure. There is a great unmet need for effective therapies in this disease. After clinical trials of more than 30 potential drugs to treat ALS, we still have only two that slow the disease progression."

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ALS can rapidly progress in some people, leading to death in 6 months to 2 years after diagnosis. For this reason, it is difficult to enroll people in clinical trials, a reality that supports development of a corresponding animal model, Dr. Davis said.

In addition, prevention remains essential. "This is a pre-clinical model, which is really the most important type of model, because once people have full-blown disease, it's hard to reverse or slow its progression," he added.

The research builds on earlier findings from Dr. Davis and colleagues in a 2016 study that demonstrated cyanotoxin BMAA can cause changes in the brain that resemble Alzheimer's disease in humans, including neurofibrillary tangles and amyloid deposits.

Even with the promise of L-serine, the researchers note there is a bigger picture to their new ALS animal model. "Other drugs can also be tested, making this very valuable for clinical affirmation," Davis said.

The research also has implications for Florida, as BMAA comes from harmful blue-green algae blooms, which have become more common in the summer months in Florida.

According to Larry Brand, Ph.D., professor of marine biology at the Rosenstiel School at the University of Miami, "We have found that the BMAA from these blooms has biomagnified to high concentrations in South Florida aquatic food chains, thus our seafood."

We are very curious about how BMAA affects individuals in South Florida. That's our next step."

Dr. David A. Davis, Ph.D., lead author

Future research could attempt to answer multiple questions, including: How common is BMAA in local seafood? What are the risks of exposure through exposure to aerosolized cyanotoxins? Is there a specific group of people who are more vulnerable from this exposure to developing diseases like Alzheimer's and ALS?

The current research would not have been possible, Dr. Davis said, without interdisciplinary collaboration both inside and outside the University of Miami. Another essential factor is the "very unique research environment" in the UM Department of Neurology. For example, the Brain Endowment Bank allows Miller School researchers access to other investigators and to essential research material.

Source:

University of Miami Miller School of Medicine

Journal reference:

Davis, D.A., et al. (2020) L-Serine Reduces Spinal Cord Pathology in a Vervet Model of Preclinical ALS/MND. Journal of Neuropathology & Experimental Neurology. doi.org/10.1093/jnen/nlaa002.