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Researchers at the Johns Hopkins Bloomberg School of Public Health contributed to a new U.S. Centers for Disease Control and Prevention report that finds the prevalence of autism spectrum disorder (ASD) among 11 surveillance sites as 1 in 54 among children aged 8 years in 2016 (or 1.85 percent). This is a 10 percent increase from the most recent report two years ago when it was 1 in 59, and the highest prevalence since the CDC began tracking ASD in 2000. Consistent with previous reports, boys were 4 to 5 times more likely to be identified with ASD than girls. The rate for ASD is 1 in 34 among boys (or 2.97 percent) and 1 in 145 among girls (or 0.69 percent).

ASD is a developmental disorder characterized by social and communication impairments, along with limited interests and repetitive behaviors. Early diagnosis and intervention are key to improving learning, communication, and other skills. Rates have been rising dramatically in the past three decades, but researchers do not know how much of this rise is due to better detection or an increase in "true" cases or both. Technical factors that may be contributing to an increase in ASD include increased awareness, screening, diagnostic services, treatment and intervention services, better documentation of ASD behaviors, and changes in diagnostic criteria. To date, the causes of autism are not completely understood but studies show that both environment and genetics may play a role.

As in its prior report, the CDC collected data at 11 regional monitoring sites across the U.S. that are part of the Autism and Developmental Disabilities Monitoring (ADDM) Network. The ADDM Network makes its estimates in the participating communities by reviewing health and/or education records to ensure as complete a count as possible. ADDM does not rely solely on the presence of a documented ASD diagnosis; it also counts ASD cases determined by ADDM expert clinicians who review the records.

The Maryland-ADDM monitoring site is based at the Johns Hopkins Bloomberg School of Public Health.

This is the seventh report by the ADDM Network, which has used the same surveillance methods each time. Estimated prevalence rates of ASD in the U.S. reported by previous data were:

one in 59 children in the 2018 report based on 2014 data

one in 68 children in the 2016 report based on 2012 data

one in 68 children in the 2014 report based on 2010 data

one in 88 children in the 2012 report based on 2008 data

one in 110 children in the 2009 report based on 2006 data

one in 150 children in the 2007 report based on 2000 and 2002 data

"We need to know how many children have ASD in order to prepare our communities and services systems," says Li-Ching Lee, PhD, ScM, a psychiatric epidemiologist with the Bloomberg School's departments of Epidemiology and Mental Health and the principal investigator for Maryland-ADDM. "An ongoing and accurate estimate will help to develop realistic plans to support these children now, and later into their adolescence and adulthood."

For the first time in ADDM's history, researchers found no statistically significant difference in the ASD prevalence between black and white children. This may suggest progress toward earlier and more equitable identification of ASD, the researchers say.

"Although the gap related to the prevalence of racial and ethnic differences is closing, disparities in early intervention persist for racial and ethnic minorities," Lee said. "Black and Hispanic children with ASD were evaluated at older ages and were more likely to have intellectual disability than white children." Later diagnosis can hinder early intervention, considered the most effective treatment for ASD.

In Maryland, the prevalence of ASD was 1 in 52 children: 1 in 33 for boys and 1 in 128 for girls. The data were derived from health and special education records of children who were 8 years old and living in Baltimore County in 2016.

ASD can be diagnosed as early as 24 months of age. In Maryland, however, only 48.3 percent of children with ASD received a comprehensive evaluation by 36 months, and the median age at earliest ASD diagnosis was 48 months. "This lag may delay the timing for children with ASD to get diagnosed and receive needed services," says Lee, who is an associate director of the school's Wendy Klag Center for Autism and Developmental Disabilities.

The CDC recommends that parents track their child's development, act quickly, and get their child screened if they have a concern. Free checklists and information for parents, physicians, and child care providers are available at http://www.cdc.gov/ActEarly.

A full copy of the report, "Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years--Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2016" is available on the CDC website: https://www.cdc.gov/mmwr/volumes/69/ss/ss6904a1.htm?s_cid=ss6904a1_w.

A copy of the Community Report with individual state statistics is available: https://www.cdc.gov/ncbddd/autism/addm-community-report/index.html.

Boys with Duchenne muscular dystrophy (DMD) experience poor muscle regeneration, but the precise reasons for this remain under investigation. An experimental model of severe DMD that experiences a large spike in transforming growth factor-beta (TGFβ) activity after muscle injury shows that high TGFβ activity suppresses muscle regeneration and promotes fibroadipogenic progenitors (FAPs). This leads to replacement of the damaged muscle fibers by calcified and connective tissue, compromising muscle structure and function. While blocking FAP buildup provides a partial solution, a Children's National Hospital study team identifies correcting the muscle micro-environment caused by high TGFβ as a ripe therapeutic target.

The team's study was published online March 26, 2020, in JCI Insight.

DMD is a chronic muscle disease that affects 1 in 6,200 young men in the prime of their lives. The disorder, caused by genetic mutations leading to the inability to produce dystrophin protein, leads to ongoing muscle damage, chronic inflammation and poor regeneration of lost muscle tissue. The patients experience progressive muscle wasting, lose the ability to walk by the time they're teenagers and die prematurely due to cardiorespiratory failure.

The Children's National team finds for the first time that as early as preadolescence (3 to 4 weeks of age), their experimental model of severe DMD disease showed clear signs of the type of spontaneous muscle damage, regenerative failure and muscle fiber loss seen in preadolescent boys who have DMD.

"In boys, the challenge due to muscle loss exists from early in their lives, but had not been mimicked previously in experimental models," says Jyoti K. Jaiswal, MSc, Ph.D., principal investigator in the Center for Genetic Medicine Research at Children's National, and the study's co-senior author. "TGFβ is widely associated with muscle fibrosis in DMD, when, in fact, our work shows its role in this disease process is far more significant."

Research teams have searched for experimental models that replicate the sudden onset of symptoms in boys who have DMD as well as its complex progression.

"Our work not only offers insight into the delicate balance needed for regeneration of skeletal muscle, but it also provides quantitative information about muscle stem cell activity when this balanced is disturbed," says Terence A. Partridge, Ph.D., principal investigator in the Center for Genetic Medicine Research at Children's National, and the study's co-senior author.

"The D2-mdx experimental model is a relevant one to use to investigate the interplay between inflammation and muscle degeneration that is seen in humans with DMD," adds Davi A.G. Mázala, co-lead study author. "This model faithfully recapitulates many features of the complex disease process seen in humans."

Between 3 to 4 weeks of age in the experimental models of severe DMD disease, the level of active TGFβ spiked up to 10-fold compared with models with milder disease. Intramuscular injections of an off-the-shelf drug that inhibits TGFβ signaling tamped down the number of FAPs, improving the muscle environment by lowering TGFβ activity.

"This work lays the foundation for studies that could lead to future therapeutic strategies to improve patients' outcomes and lessen disease severity," says James S. Novak, Ph.D., principal investigator in Children's Center for Genetic Medicine Research, and co-lead study author. "Ultimately, our goal is to improve the ability of patients to continue to maintain muscle mass and regenerate muscle."

What The Study Did: This randomized clinical trial compared how effectively high-dose, targeted radiation therapy versus no treatment (observation) among 54 men prevented the progression over six months of recurrent hormone-sensitive prostate cancer that has metastasized to a small number of sites in the body.

Authors: Phuoc T. Tran, M.D., Ph.D., of the Johns Hopkins University School of Medicine in Baltimore, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamaoncol.2020.0147)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Osaka, Japan - Geographically isolated from mainland Eurasia, the island nation of Japan has seen little in the way of population mixing for thousands of years. In fact, after two waves of human migration—one 40,000 years ago from Southeast Asia and one 3,000 years ago from the Korean Peninsula—Japanese people are recognized as a relatively homogeneous and isolated population.

But in a study published in Nature Communications, an international research team led by Osaka University revealed that there is more than meets the eye when it comes to the Japanese population.

"At first glance, the Japanese population appears to be demographically homogenous," says lead author of the study Saori Sakaue. "However, there are obvious cultural and linguistic differences from region to region and from island to island in Japan, leading us to suspect that there may actually be greater population structure than has previously been shown."

Using novel machine-learning methods, the researchers examined the genomic sequences of 170,000 individuals from Japan, looking for minute genetic differences. As it turns out, they were right.

"Dimensionality reduction analyses revealed fine-scale diversity within the Japanese population," explains Sakaue. "Not only did we identify the two main population clusters observed in previous studies, we successfully distinguished eight sub-clusters within one of these populations, confirming that Japanese people are not as homogenous as we previously thought."

Interestingly, the eight sub-clusters correlated with distinct islands located in the Ryukyu region of Japan, some of which are separated by as little as 50 km.

The researchers also successfully illuminated genetic diversity within populations from the United Kingdom, Malaysia, and an Arab cohort, suggesting that the machine-learning approach is also applicable to more complex populations.

They then turned their attention to the implications of their research, particularly the future disease risk prediction of individuals based on their unique genetic profile.

"Given the fine-scale differences within the Japanese population, we were interested in how subtle population differences may affect the genetic prediction of human diseases and complex traits," explains senior author Yukinori Okada. "Using phenome-wide polygenic risk score analyses of 67 complex traits, we confirmed that the sub-structures within the Japanese population did indeed impact disease prediction."

"The results of our study have significant implications for the wider field of individualized medicine, highlighting the importance of a thorough understanding of genetic diversity before embarking on disease prediction."

Acupuncture can reduce migraine headaches compared to both sham (placebo) acupuncture and usual care, finds a new trial from China published by The BMJ today.

The researchers say doctors should provide information about acupuncture as an option when discussing preventive treatment strategies with patients.

More than one billion people worldwide are affected by migraine. It has considerable impact on quality of life and imposes a substantial burden on society.

For people with frequent migraines, preventive treatments to reduce headache frequency are available, but not all patients respond well to drug therapy and many prefer to avoid it. Evidence for the benefit of acupuncture on migraine prevention has been mixed.

So a team of researchers based in China set out to compare the effectiveness of manual (real) acupuncture with sham (placebo) acupuncture or usual care.

Their findings are based on 147 patients (average age 37) with a history of migraine without aura who were recruited from seven hospitals in China from June 2016 to November 2018.

None of the patients had received acupuncture before, and all were instructed not to take any painkillers or start any other treatments during the trial.

After four weeks of baseline assessment, patients were randomly allocated to receive either 20 sessions of manual acupuncture at true acupuncture points, 20 sessions of non-penetrating sham acupuncture at non-acupuncture points, or usual care (including advice on lifestyle and self-management) over eight weeks.

Over the next 12 weeks, the researchers compared changes in migraine days and migraine attacks per four-week period from baseline.

Compared with sham acupuncture, manual acupuncture resulted in a greater reduction in migraine days (3.9 v 2.2) at weeks 13 to 20 and migraine attacks (2.3 v 1.6) at weeks 17 to 20, with an apparent increasing trend.

The adjusted difference between manual and sham acupuncture was 1.4 fewer migraine days at weeks 13 to 16, and 2.1 fewer migraine days and at weeks 17 to 20.

Sham acupuncture resulted in a minor reduction in migraine attacks compared with usual care (1.6 v 0.4) during weeks 17 to 20, with a slightly decreasing trend over this period.

No severe adverse events were reported.

The researchers point to some limitations, such as the relatively short (20 week) study period. Strengths include use of a non-penetrating needle for sham acupuncture, and successful blinding to increase the reliability of the results.

These results show that treatment with manual acupuncture compared to sham acupuncture or usual care, "resulted in a significantly higher reduction in the frequency of migraine days and migraine attacks," write the authors.

They say acupuncture "can be recommended as a prophylactic treatment" and clinicians "should provide patients with information about acupuncture as an option when discussing prophylactic treatment strategies."

And they call for longer term studies to assess how long the effects of acupuncture would last.

"We now have good evidence that acupuncture is an effective treatment for episodic migraine," writes Heather Angus-Leppan, a consultant neurologist at the Royal Free London NHS Foundation Trust, in a linked editorial.

She acknowledges that the effects of acupuncture (and other preventive treatments) are a modest reduction in migraine days each month, and it is difficult for clinicians to know whether this level of benefit would be noticeable to patients until we have long-term data.

But she says, given that almost 90% of people with frequent migraine have no effective preventive treatment, "acupuncture provides a useful additional tool in our therapeutic armoury."

This study "helps to move acupuncture from having an unproven status in complementary medicine to an acceptable evidence based treatment," she concludes.

CORVALLIS, Ore. -- It's a self-perpetuating cycle: Kids with developmental disabilities face challenges in building motor skills, which makes them less able to participate in routine physical activity, which gives them less opportunity to practice those same motor skills.

But parents can make a big difference by modeling and supporting physical activity in daily life, especially with younger children, a recent study from Oregon State University found.

"When we see 12-year-olds playing soccer, we'll have some 12-year-olds with developmental disabilities, and their motor skills might look more like a 6-year-old," said researcher Megan MacDonald in OSU's College of Public Health and Human Sciences, who studies movement and physical activity in children. "If we can give them more opportunities to improve those motor skills, they'll have more opportunity to engage in those activities."

Gross motor skills like jumping and running, and object control skills like throwing and catching, are the building blocks upon which more complex physical activity can be learned as children grow, so the sooner kids work on being active, the better, MacDonald said.

The study, published last month in the Disability and Health Journal, surveyed 135 parents of children with developmental disabilities ages 5-7, and found that parents who reported spending more time on these physical activities observed better motor skills in their children.

Survey questions about "parental explicit modeling" asked parents how often they and their family engaged in physical activity, as well as how they used their own behavior to encourage activity. "Parental tangible support" included creating a supportive environment with actions like driving kids to and from recreational activities and watching their games or activities.

Both factors had a significant positive impact on increasing physical activity among children, which then positively impacted the development of the children's motor skills.

Intervening early sets children up to have more opportunity for physical activity in the future, and takes advantage of the fact that younger kids already spend more time watching and copying their parents, MacDonald said.

Parents of children with developmental disabilities have more to think about than parents whose children don't have disabilities, she said: They might want to prioritize working on social and communication skills, and it's possible physical activity is less of a priority.

"But we're trying to say, 'Hey, in physical activity, you can focus on other things too,'" such as teaching social skills or reciprocal communication during a game on the playground, MacDonald said. "So, taking your kid to the park, providing these opportunities, counts on many levels. It's fun and it's healthy."

"And how you act as a parent is something all kids pick up on, including children with developmental disabilities."

The pediatric brain cancer known as diffuse intrinsic pontine glioma (DIPG) is almost uniformly fatal. In part, this is due to where and how it grows, forming as a diffuse net of cells in a part of the brainstem called the pons, which controls essential functions like breathing and swallowing. Another factor that makes DIPG especially dangerous is a lack of treatments - currently, there are no targeted therapies or immunotherapies proven effective to treat the condition, and the many chemotherapy clinical trials seeking to treat DIPG have been uniformly unsuccessful.

In fact, chemotherapy has been so unsuccessful against DIPG that researchers have questioned whether chemotherapy drugs are even able to reach the cancer. There is reason to believe they might not: Many drugs are unable to cross the blood-brain barrier that encapsulates the brain and central nervous system, and the pons is especially hard to reach. Now a study by University of Colorado Cancer Center researchers working at Children's Hospital Colorado and published in the journal Neuro-Oncology Advances offers insight into this question.

"The results were surprising and encouraging," says Adam Green, MD, CU Cancer Center investigator and pediatric brain cancer specialist at Children's Hospital Colorado. "The bottom line is that it looks like the medicine does reach DIPG tissue in good quantities that have the potential to be effective against the tumor."

In other words, the reason chemotherapy has been ineffective against DIPG is most likely the fact that we haven't found the right chemotherapy yet.

In the clinical trial, done in collaboration with Michael Wempe, PhD, director of the Medical Chemistry Core Facility at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, investigators gave one dose of the chemotherapy drug gemcitabine to newly diagnosed DIPG patients and then measured how much of this chemotherapy was present in patients' tumor tissue on their biopsy performed immediately afterward. The group also performed parallel studies in mouse models of human DIPG. The results in humans and mice were similar, independent of exactly where the tumor grew in the brain, and held across a few known tumor subtypes.

"We don't expect the one dose of chemo to be effective against the tumor, and so we were really asking families to take a leap of faith with us - to trust that it would be safe and that it would help answer an important question, both for their child and for future patients. To be the first family and patient was a really brave decision on their part," Green says.

"This research makes us very happy," says the father of the first child enrolled. "The fact that our daughter contributed makes us proud. Also, the experiment was so elegant in its design. I remember thinking how propitious it was to give a single dose of gemcitabine immediately before the biopsy she already needed to have. What a perfect way to test something that desperately needed testing but was otherwise untested and untestable!"

Importantly, the Children's Hospital Colorado team is a leading center for the treatment of pediatric brain cancer and has helped pioneer tumor biopsy as a standard part of DIPG treatment.

"We wouldn't biopsy a patient's brain just to look for chemotherapy. But because this is part of our standard procedure for diagnosis and treatment, we were able to also look in biopsy tissue for the accumulation of chemotherapy. It made us uniquely positioned to do this trial," Green says.

Green sees the state of DIPG as similar to the treatment of pediatric leukemia in the 1950s or pediatric neuroblastoma in the 1990s, both of which were incurable at the time, but for which new treatments have dramatically improved outcomes.

"These diseases required combination treatment approaches, and that's what we're aiming for," Green says.

The current finding, while preliminary, also has the potential to influence the focus and design of DIPG clinical trials. For example, another treatment strategy has been to explore the direct delivery of chemotherapy drugs to tumor tissue in ways that bypass the blood-brain barrier. The current study implies that in addition to innovative drug-delivery strategies, the field can continue to prioritize the search for new, better chemotherapy drugs to be delivered via the standard method of infusion.

"It's encouraging," Green says. "This shows that systemic chemotherapy could be part of the answer in treating these tumors. We just have to apply all we're learning about the biology of the tumors to find the right medicines. It gives us a lot of hope that if we find the right medicines, we'll be able to treat this tumor effectively."

What The Viewpoint Says: Emerging as an acute infectious disease, COVID-19 may be- come a chronic epidemic similar to influenza because of genetic re- combination. Therefore, we should be ready for the reemergence of COVID-19 or other coronaviruses.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamacardio.2020.0934)

Editor's Note: The article includes funding/support disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

A medication commonly used to treat non-small cell lung cancer that has spread, or metastasized, may have benefits for patients with metastatic brain cancers, suggests a new review and analysis led by researchers at St. Michael's Hospital of Unity Health Toronto and Harvard Medical School.

Published today in JAMA Network Open, the research hones in on osimertinib, a treatment recently approved in North America as a therapy for metastatic non-small cell lung cancer with a specific mutation.

In a meta-analysis of 15 studies with 324 patients, researchers found that 64 per cent of patients with metastatic brain cancer whose cancer had spread from their lungs and were part of clinical trials with this therapy experienced a measurable response, and 90 per cent experienced disease control in the central nervous system. Up to 40 per cent of patients, however, reported severe side effects from the treatment.

"The development of brain metastases is an often feared complication of cancer," said Anders Erickson, a graduate student at St. Michael's Hospital in Dr. Sunit Das' lab, who led this research.

"Cancers that spread to the brain have historically required radical treatment with surgery or radiation. Chemotherapies that are capable of killing cancer cells in the rest of the body are unable to penetrate the blood-brain barrier."

There is a lack of evidence to support the use of targeted therapy - or small molecules that target the specific drivers of a cancer - in metastatic brain disease. The researchers set out to fill this gap by further analyzing whether this targeted treatment, known for its ability to cross the blood-brain barrier, might be beneficial to patients whose lung cancer had spread to the brain.

"Though more research is needed, our study supports the potential role this therapy could play for patients," said Dr. Das, a scientist at the Keenan Research Centre for Biomedical Science and a neurosurgeon at St. Michael's.

"It suggests we may one day be able to treat these patients without the concerns associated with surgery and radiation."

The scientists aim to investigate this topic on a broader scale, looking at larger data sets to survey the impact of different targeted therapies for metastatic brain cancer.

"We hope our work will contribute to knowledge that will inform future treatment and move the needle for patients with metastatic brain cancer in the era of precision medicine," Erickson said.

Denver--March 25, 2020-- Lung cancer clinical trials supported by the pharmaceutical industry demonstrate no more bias compared to studies funded by other sources, according to a study published in the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer.

Clinical trials are expensive and often require funding from the pharmaceutical industry, but previous studies have revealed bias in clinical studies conducted by industry sponsors.

Pedro Aguiar Jr, M.D., M.Sc., Ph.D., M.B.A., Faculdade de Medicina do ABC Santo André, Brazil and his research team sought to determine if any bias existed among pharmaceutical-backed studies of therapies for non-small cell lung cancer patients. His group compared studies funded by drug companies with studies funded by other sources in terms of costs, reported results and strength of evidence.

Dr. Aguiar analyzed 477 studies focusing on non-small cell lung cancer that were published between 2012 and 2017. His analysis focused on 275 trials sponsored by the pharmaceutical industry and 202 funded by other sources. These studies included 85,328 patients -- 64,434 in studies sponsored by the PI and 20,894 in studies with other funding sources.

Dr. Aguiar's group assessed the risk of the following biases: randomization bias, allocation bias, performance bias, detection bias, attrition bias and reporting bias.

The authors write that industry interests may determine the types of research questions to be answered by clinical trials, as well as their experimental design. Previous studies suggest that even the results of some trials may be affected by industry-vested interests through several types of systematic errors such as reporting bias and violation of the uncertainty principle. The emphasis on the reporting and dissemination of positive results may favor a higher rate of reporting in comparison with negative ones.

Previous studies also suggest that even the results of some trials may be affected by industry-vested interests through several types of systematic errors such as reporting bias and violation of the uncertainty principle.

However, Aguiar's analysis of clinical trials focusing on non-small cell lung cancer did not reveal any such bias.

"We found that studies funded by the pharmaceutical industry had stronger evidence, evaluated more innovative therapies and resulted in a higher proportion of open access manuscripts than studies supported by other funding sources," Dr. Aguiar said. There was no significant difference regarding the reporting of experimental arm superiority between the two groups or the risk of bias, he added.

In the United States, the amount of money available for the National Institutes of Health to invest in one year is approximately $39 billion, whereas the amount spent by the pharmaceutical industry per year amounts to approximately $100 billion. During the five years considered in this review, the proportion of studies funded by the pharmaceutical industry increased from 49% in 2012 to 65% in 2017.

"In our study, the results of pharmaceutical industry-sponsored trials did not favor the experimental arms compared with other sources of funding and the reporting bias was considered low for almost 90% of all included studies," Dr. Aguiar said.

An international team of researchers led by the Universities of Bonn and Ulm has investigated how a cell's own "protein shredder" can be specifically programmed to fight cancer. The researchers were able to demonstrate the degradation of proteins that are overly active in breast cancer, for example. The results are published in the renowned journal "Chemical Science".

Cells continuously produce proteins to be able to carry out their tasks in the body. Any protein molecules that are no longer needed are given a kind of "disposal sticker". All proteins with such a label are then crushed and recycled by a cell's own shredder, the proteasome.

For some years, researchers have been trying to harness this mechanism selectively in the fight against diseases such as cancer. After all, tumor cells also require certain proteins. If it was possible to attach a disposal label to them, they would inevitably be shredded by the proteasome, which would inhibit the growth of the cancer cell.

This approach has indeed already proven to be effective in the test tube. Here, scientists use so-called PROTACs (the abbreviation stands for "proteolysis targeting chimeras"). "However, producing these substances is very complicated," explains Prof. Dr. Michael Gütschow from the Pharmaceutical Institute of the University of Bonn. "We have investigated which strategies are promising in this respect and how particularly effective PROTACs can be customized, so to speak."

Molecular hybrids

PROTACs are molecular hybrids: They consist of both a molecular part that docks to the cancer protein, as well as a structure that can bind to the labeling enzymes. Both units are connected by a kind of arm. PROTACs thus bring the target protein and the labeling machine together, thereby ensuring that the harmful protein is given a disposal label.

"We have synthesized many molecules, among other things to find out what structure and length the arm must have in order to label the protein as effectively as possible," explains Christian Steinebach from the Pharmaceutical Institute of the University of Bonn. In addition, the researchers optimized another aspect of the PROTACs. Each cell has dozens of different labeling enzymes called ubiquitin ligases. Not all of them work equally well with every protein. "We have therefore produced and tested different PROTACs for different ligases," says Dr. Jan Krönke from Ulm University Medical Center.

The active substances developed target a protein that ensures that cancer cells can multiply better. The PROTACs now cause the cell's own shredder to destroy the protein. "In experiments with cell cultures, we were able to show that our PROTACs actually significantly reduce the cellular concentration of this protein and effectively suppress the growth of cancer cells," explains Dr. Krönke. "The substances now allow us to study proteins that are important for the tumor in more detail."

The universities of Bonn and Ulm are among the leading institutions in Germany in the young field of PROTAC research. "Our study shows prototypically which techniques can be used to produce and specifically optimize these active substances," says Gütschow. There is great interest in such strategies, since PROTACs are regarded as an important beacon of hope for the treatment of serious diseases.

New Rochelle, NY, March 25, 2020--The need for accurate and informative labeling of hemp and hemp-derived cannabidiol (CBD) products is a critical public health issue. Despite CBD being a U.S. Food and Drug Administration-approved drug, it is increasingly being added to food, beverages, and nutritional supplements, often with misleading labeling or marketing claims, according to an article published in Cannabis and Cannabinoid Research, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article free on the Cannabis and Cannabinoid Research website through April 25, 2020.

Jamie Corron ND, MPH, The Center for Medical Cannabis Education (Del Mar, CA) and colleagues coauthored the article entitled "Labeling of Cannabidiol Products: A Public Health Perspective." Accurate and informative labeling can help protect consumers from untruthful or unsubstantiated claims and from unallowed drug claims that may lead them to forego treatments supported by the medical evidence. Other risks include the failure to include CBD on a label, or its correct amount. The article by Corron et al. helps manufacturers understand the basic framework for FDA labeling and marketing regulations.

Editor-in-Chief Daniele Piomelli, PhD, University of California-Irvine, School of Medicine, states: "Good public health starts with good public health information. Now that products containing CBD have gained immense popularity, often undeservedly, clear and truthful labeling has become a must."

Irvine, CA - March 25, 2020 - Researchers from the University of California, Irvine have conducted a statistical analysis that predicts more than 70,000 heart attacks, strokes and other adverse cardiovascular events could be prevented each year in the U.S. through the use of a highly purified fish oil therapy.

Led by Nathan D. Wong, PhD, professor and director of the Heart Disease Prevention Program in the Division of Cardiology at the UCI School of Medicine, the abstract of the statistical analysis was accepted by the American College of Cardiology and is slated to be presented at the upcoming ACC.20/World Congress of Cardiology virtual conference taking place March 28-30. The analysis utilizes data from the Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey (NHANES), and inclusion criteria from a multinational clinical trial led by investigators from Harvard University called REDUCE-IT, which was published in the New England Journal of Medicine in January of 2019.

The REDUCE-IT trial showed patients with known cardiovascular disease or diabetes and multiple risk factors who have elevated triglyceride levels and are at increased risk for ischemic events benefitted substantially from icosapent ethyl, a highly purified fish oil therapy, which lowered cardiovascular events, including heart attacks and strokes, by 25 percent. Positive results were not found in other trials, possibly due to mixtures with other omega-3 fatty acids such as DHA, or inadequate dosages according to Wong.

"Our analysis extends the findings of the REDUCE-IT trial by estimating its potential impact on the U.S. population," said Wong. "By using inclusion criteria and cardiovascular disease event rates from the REDUCE-IT trial and applying it to data on US adults from NHANES, we were able to estimate the beneficial impact icosapent ethyl could have on preventing initial and total cardiovascular events in eligible U.S. adults with cardiovascular disease or diabetes and multiple risk factors."

Wong's analysis is the first to project the findings of REDUCE-IT to the overall U.S. population.

"When you consider that for every 21 patients treated with icosapent ethyl you can spare a cardiovascular event, you begin to see the implications of our results," said Wong.

Icosapent ethyl is a purified stable eicosapentaenoic acid (EPA) which was recently approved by the Federal Drug Administration (FDA) in conjunction with maximally tolerated statin therapy to reduce the risk of cardiovascular events in certain adults with elevated triglyceride levels. The only drug of its kind to show such an effect, icosapent ethyl, is currently marketed under the name Vascepa® by Amarin Pharma. The EPA therapy has also gained the support of several major societies, which have incorporated it in various guidelines, scientific statements and advisories, including the American Diabetes Association, American Heart Association, National Lipid Association, and the European Society of Cardiology/European Atherosclerosis Society.

Bottom Line: A HER2-targeted antibody-drug conjugate, fam-trastuzumab deruxtecan-nxki (Enhertu), showed signs of clinical activity in multiple non-breast/non-gastric cancer types, according to results from a phase I study.

Journal in Which the Study was Published: Cancer Discovery, a journal of the American Association for Cancer Research

Author: Lead author: Junji Tsurutani, MD, PhD, medical oncologist at the Advanced Cancer Translational Research Institute at Showa University in Tokyo; Senior author: Bob Li, MD, medical oncologist at Memorial Sloan Kettering Cancer Center

Background: Human epidermal growth factor receptor 2 (HER2) is a gene that can promote cancer progression when mutated or expressed at high levels. High expression levels of HER2 have been observed in many different cancer types, including breast, gastric, lung, and colorectal cancers. Several HER2-targeted therapies are approved for the treatment of HER2-overexpressing breast cancer, and one such therapy is approved for gastric cancer.

"HER2-targeted therapies have proven successful for patients with breast and gastric cancers; however, there are no approved HER2-targeted therapies available for patients with other HER2-overexpressing or HER2-mutated malignancies," said Li. "Conventional therapies for these other HER2-overexpressing cancers tend to have limited efficacy and considerable side effects. Additional treatment options are urgently needed for these patients."

"Therapies that target HER2 can be selectively directed to HER2-overexpressing or HER2-mutated cancer cells, which could improve efficacy and help reduce toxicities caused by off-target effects on normal cells," said Tsurutani. Moreover, advances in diagnostic testing have improved clinicians' ability to determine a tumor's HER2 status and have thus expanded the population of patients who might benefit from HER2-targeted therapies, explained Tsurutani.

In this phase I study, Tsurutani, Li, and colleagues tested the safety and clinical activity of the HER2-targeted antibody-drug conjugate (ADC) fam-trastuzumab deruxtecan-nxki (T-DXd) in patients with several different advanced HER2-overexpressing or HER2-mutated solid tumors. T-DXd combines a cytotoxic inhibitor of DNA replication called DXd with an antibody directed to HER2. The antibody selectively binds to HER2-expressing cancer cells, and DXd is then released into the target cell, where its inhibitory effect on DNA replication leads to cell death. DXd can also enter and kill neighboring cancer cells due to its ability to pass through cell membranes. Results published within the last year demonstrated promising antitumor activity of T-DXd in HER2-overexpressing breast and gastric cancers. In December 2019, T-DXd was granted accelerated approval by the U.S. Food and Drug Administration for the treatment of patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior treatments with HER2-targeted therapy in the metastatic setting.

How the Study was Conducted: The latest publication reports data from 60 patients with HER2-overexpressing non-breast/non-gastric solid tumors and/or HER2-mutated solid tumors. Of the 60 patients, 20 had colorectal cancer, 18 had non-small cell lung cancer (NSCLC), and 22 were classified as having "other" cancer types. "Other" cancer types included salivary gland tumors (eight patients), esophageal cancer (two patients), endometrial cancer (two patients), biliary tract cancer (two patients), Paget's disease (two patients), pancreatic cancer (one patient), uterine cervix carcinoma (one patient), extraskeletal myxoid chondrosarcoma (one patient), and small intestine adenocarcinoma (one patient). Additionally, two cases of HER2-mutated breast cancer were included in this category.

Results: All 60 patients were evaluated for response. The overall objective response rate was 28.3 percent with a median progression-free survival of 7.2 months. The median overall survival was 23.4 months. The objective response rate was greatest for NSCLC, with 55.6 percent of patients having a confirmed objective response (10 partial responses). In HER2-mutant NSCLC, the objective response rate was 72.7 percent (8 partial responses). The objective response rates for colorectal cancer and "other" cancer types were 5 percent (one partial response) and 27.3 percent (five partial responses and one complete response), respectively.

The frequency of treatment-emergent adverse events (TEAEs) was similar across the different tumor types. Overall, 62.7 percent of patients experienced a TEAE that was grade 3 or higher, and 30.5 percent experienced serious TEAEs. The most common TEAEs were anemia; decreased counts of neutrophils, white blood cells, and platelets; decreased appetite; increased levels of aspartate aminotransferase, which is a biomarker for liver damage; febrile neutropenia; and decreased blood levels of sodium. Five patients had drug-related interstitial lung disease. Five patients experienced an adverse event with a fatal outcome, of which two were reported to be treatment-related. One of the treatment-related deaths was due to drug-related interstitial lung disease. Forty-nine patients discontinued treatment due to disease progression, adverse events, death, patient withdrawal, or other reasons.

In another study published by Li and colleagues in Cancer Discovery, T-DXd led to a partial response in a patient with lung cancer who had relapsed after treatment with another HER2-targeted ADC, ado-trastuzumab emtansine (T-DM1). This study also demonstrated that T-DM1 treatment led to clinical responses in patients with HER2-mutant or amplified lung cancers, and that combining T-DM1 with an irreversible HER kinase inhibitor enhanced cellular uptake of the drug in cell culture. Furthermore, combination treatment with T-DM1 and an irreversible HER kinase inhibitor led to a partial response in a patient with breast cancer who had previously relapsed on T-DM1. Together, results from this second study suggest that T-DXd or a combination of T-DM1 and a HER kinase inhibitor could be explored as potential treatment options for patients with relapse on T-DM1.

Author's Comments: "The safety profile of T-DXd is consistent with the previously reported breast and gastric cancer cohorts from this phase I study," said Li. "Interstitial lung disease is an important identified adverse event that may be serious - even fatal - and thus requires monitoring and prompt intervention. Further research is required to minimize and manage this risk."

"T-DXd demonstrated promising antitumor activity in a heterogeneous patient population," said Tsurutani. "These results indicate that T-DXd should be explored in larger studies as a treatment option for patients with HER2-overexpressing or HER2-mutated solid tumors."

Li noted, "We are very excited by the results of this preliminary study. T-DXd shows early promise for transforming the standard of care for patients with HER2-overexpressing or HER2-mutated cancers and we look forward to continuing this important research in future clinical trials."

In regard to the second study, Li said, "This study shows the power of translational science through bench-to-bedside-and-back discoveries. This team approach has provided mechanistic understanding and helped us to develop ADCs as a potential new class of drugs for patients with lung cancers and other solid tumors."

Study Limitations: Limitations of the study include the small sample size, both overall and within each tumor type, and the limited diversity of HER2 mutations included in the study. Larger clinical trials are ongoing.

Funding & Disclosures: Both studies were funded by Daiichi Sankyo. The second study was also funded by the National Cancer Institute, the AACR-Conquer Cancer Foundation of ASCO Young Investigator Award for Translational Cancer Research, the Carol Lowenstein Fund, a gift from Mr. and Mrs. Peter Pritchard, MORE Health, Genentech, and Puma Biotechnology. Li has served as an advisor for Biosceptre International, Guardant Health, Hengrui Therapeutics, Mersana Therapeutics, Roche/Genentech, and Thermo Fisher Scientific, and he has received research grants to his institution from AstraZeneca, BioMed Valley Discoveries, Daiichi Sankyo, GRAIL, Guardant Health, Hengrui Therapeutics, Illumina, Amgen, Eli Lilly and Company, MORE Health and Roche/Genentech. Li is an inventor on two pending institutional patents at Memorial Sloan Kettering Cancer Center. Tsurutani is an advisor for Daiichi Sankyo, Eli Lilly and Company, and Asahi Kasei. Tsurutani has received honoraria from Daiichi Sankyo, Eisai, Taiho Pharmaceutical, Chugai Pharmaceutical, Kyowa Kirin, Nihon Kayaku, Novartis, Pfizer, AstraZeneca, Ono Pharmaceutical, and MSD. Tsurutani has received funds for travel from Daiichi Sankyo and research funds from Boehringer Ingelheim, Eli Lilly and Company, Eisai, and Ono Pharmaceutical.

New cases of hepatitis C amongst HIV positive men in London and Brighton have fallen by nearly 70 per cent in recent years.

An analysis of five clinics in London and Brighton found that 378 cases were diagnosed between July 2013 - June 2018. New infections peaked at 14 per 1000 people studied in 2015, falling to 4 per 1000 by 2018. The study is published in Clinical Infectious Diseases.

The researchers who led the study at Imperial College London and Imperial College Healthcare NHS Trust believe that regular hepatitis C screening and improved access to new treatments have contributed to greatly reducing the transmission of the infection. They also believe that if this progress can be maintained, London will be on track to achieve the targets set out by the British HIV Association to eliminate hepatitis C completely in people with HIV by 2021.

The researchers analysed data of more than 9,000 men at risk of hepatitis C at four centres in London and one in Brighton - St Mary's Hospital, part of Imperial College Healthcare NHS Trust, Royal Free NHS Trust, Mortimer Market Centre, Barts Health NHS Trust and Brighton & Sussex University Hospitals NHS Trust. As leading Global Fast-Track Cities for HIV, London and Brighton have demonstrated high rates of HIV treatment coverage and success. Patients at these centres were given access to regular screening and some were able to access treatment in early infection through academically-led drug trials.

Dr Lucy Garvey, Consultant in HIV/GU Medicine at Imperial College Healthcare NHS Trust and lead author of the study, said:

"Hepatitis C can sometimes cause serious liver disease and remains a major cause of global mortality. Around 2.3 million individuals worldwide are co-infected with HIV and hepatitis C and they are at greater risk of their disease progressing compared to those without HIV infection. However, with the new hepatitis C treatments, it is possible to cure the disease completely. Our study has shown how in London and Brighton, regular screening and greater access to these new treatments have resulted in a significant fall in new cases of hepatitis C and transmission of the infection."

Today's study builds on earlier work looking at hepatitis C infection in 6,000 men in London. That research showed new cases of hepatitis C amongst HIV positive men in London fell by nearly 70 per cent between 2013 and 2018. The analysis from three clinics in London found 256 men were diagnosed between 2013-2018. New infections peaked at 17 for every 1000 people studied in 2015 and fell to six by 2018. This new research, looking at a larger number of patients, is further supporting evidence that increased screening and improved access to new drugs can reduce the number of new hepatitis C infections.

Professor Graham Cooke, NIHR Professor of Infectious Diseases at Imperial College London and co-author of the paper, added:

"This study builds on our previous work and it is encouraging to see that our results have been repeated in a larger cohort of patients and in more areas in the UK. It is great news that following our study NHS England has changed its guidelines and patients will have greater access to DAA tablets through NHS services. This will have a positive impact on outcomes for patients as we work towards eliminating this disease."

Hepatitis C is a virus that infects and damages the liver. It is transmitted through blood-to-blood contact or injecting drugs. If left untreated it can lead to scarring of the liver, known as cirrhosis, and liver cancer.

People with HIV who get hepatitis C are more at risk of the disease progressing and they have a higher risk of cirrhosis and liver cancer. Hepatitis C is the leading cause of serious illness and death in people who are HIV/hepatitis C co-infected, attributing to six percent of all deaths.

Since 2016, transformational new treatments have been used to treat infection known as direct acting antiviral tablets (DAA). They are taken as tablets for 8-12 weeks and are highly effective at curing the infection in over 90 per cent of patients. Under previous NHS guidelines, those recently infected with hepatitis C had to wait six months before they could access DAA treatment. Also, if a patient acquired hepatitis C a second time, they were not eligible for a second course of DAA treatment, potentially leaving them untreated and increasing the risk of transmission.

The patients were monitored and screened every six months over the course of the study. The team found that following regular screening and treatment, cases of newly acquired acute hepatitis C have fallen sharply and in 2018 were the lowest recorded in London since 2008 for HIV positive men.

The researchers suggest that more screening, wider prescribing of hepatitis C therapies such as DAA tablets and earlier treatment of acute cases have led to a decline in acute hepatitis C cases. However, the reduction of cases still falls short of the World Health Organisation's target of 90 per cent and reinfections remain high. The team believe that there is an on-going need to promote risk reduction and design appropriate screening policies for HIV positive men.

Following the findings, NHS England have changed their guidelines on access to direct antiviral tablets (DAA). Those recently infected with hepatitis C no longer have to wait six months before they can access DAA treatment. Also, if a patient is re-infected with hepatitis C they are now eligible for a second course of DAA.