Posts Tagged ‘neurology’


Nourianz is the first adenosine A2A receptor antagonist approved for use in Parkinson Disease

By Brian Park

The Food and Drug Administration (FDA) has approved Nourianz (istradefylline; Kyowa Kirin) tablets as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson disease (PD) experiencing “off” episodes.

Nourianz is an oral selective adenosine A2A receptor antagonist and non-dopaminergic pharmacologic option. Adenosine A2A receptors are found in the basal ganglia of the brain where degeneration or abnormality is noted in PD; the basal ganglia are involved in motor control.

The approval was based on data from four 12-week, randomized, placebo-controlled clinical trials that evaluated the efficacy and safety of Nourianz in 1143 patients with PD taking a stable dose of levodopa/carbidopa with or without other PD medications.

Results from all 4 studies have demonstrated a statistically significant decrease from baseline in daily “off” time in patients treated with Nourianz compared with placebo. Regarding safety, the most common treatment-emergent adverse reactions were dyskinesia, dizziness, constipation, nausea, hallucination, and insomnia.

“Istradefylline is an Adenosine A2A receptor antagonist, and is a novel non-dopaminergic pharmacologic approach to treating OFF episodes for people living with PD,” said Dr Stuart Isaacson, MD, Parkinson’s Disease and Movement Disorders Center of Boca Raton, Florida. “Based on data from four clinical studies, istradefylline taken as an adjunct to levodopa significantly improved OFF time and demonstrated a well-tolerated safety profile. Istradefylline represents an important new treatment option for patients with Parkinson’s disease who experience ‘OFF’ episodes.”

The FDA had accepted the resubmitted NDA for Nourianz in April 2019 after previously rejecting the submission in 2008 due to concerns over efficacy findings.

For more information visit kyowakirin.com.

FDA Approves New Adjunct Treatment for Parkinson Disease

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by Nicole Fisher

Friday evening The Lancet Neurology published a new study concluding that a handheld portable device and blood test could help detect real-time brain injuries, even if a CT scan does not. Findings from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study suggest that technology might be able to fill a significant gap in emergency departments, sport fields and battle fields. Within as little as 15 minutes, patients who might have otherwise gone undiagnosed can be identified.

Although concussions and brain injuries are still greatly misunderstood, each year 4.8 million people in the U.S. visit the emergency room to be evaluated for a brain injury, and 82% of those have a head CT scan performed to test for TBI. Further, according to the Defense and Veterans Brain Injury Center, more than 380,000 military members have sustained TBIs over the past 20 years. But the most troubling part of brain injury statistics is that previous research found half of concussions go undetected and undiagnosed. That’s millions a year.

One of the main reasons is that current tools are not capable of detecting all brain injuries. Thus, even for those who do suspect an injury, cognitive and neurological questionnaires and CT scans simply cannot do the job well enough. And in situations like those following an accident or during combat, missing a diagnosis or waiting days for one could have significant consequences. But new blood-based biomarkers are emerging as an important tool to detect TBI.

Unfortunately, the field of neuroscience – and brain injuries in particular – have gotten a lot of attention over the last decade, but with much of the literature and many claims going unsubstantiated, or unable to be validated and replicated. But the authors of this article claim that the large, prospective cohort design and dynamic partnerships of TRACK-TBI are what make these results different, important, and exciting.

The TRACK-TBI study is one of the largest concussion studies of its kind, having evolved from the largest and most comprehensive natural history study of TBI ever conducted in the U.S. Led by the University of California San Francisco (UCSF), funding for the study comes from the National Institute of Neurological Disorders and Stroke (NINDS) and the U.S. Department of Defense (DOD), through U.S. Army Medical Research and Materiel Command (USAMRMC) and U.S. Army Medical Materiel Development Activity (USAMMDA), as well as funding from philanthropic and private partners, like Abbott.

According to Geoffrey T. Manley, M.D., Ph.D., the principal investigator of TRACK-TBI and a neurosurgeon and professor of neurosurgery at UCSF, “We all have a unified, common goal to advance technologies that provide objective information about what’s happening to the brain. The brain and brain injury are extremely complex. So, this work and the results are really about the power of partnership.”

In 2014, the DOD and Abbott partnered to begin working on developing a portable blood test that helps assess concussions right at a person’s side. And the military continues to use Abbott’s current i-STAT system, a handheld blood analyzer that carries out a range of clinical tests. Building on this, with its involvement in TRACK-TBI, Abbott now has more than 120 scientists devoted to researching and developing the concussion assessment test for the next generation of i-STAT™ Alinity™ system.

A critical part of the TRACK-TBI research initiative is to evaluate the effectiveness of blood-based biomarkers to detect brain injury.Consequently, the goal of this collaboration is to have a blood test based on robust, proven data that can easily be utilized in the military, on the field, and in hospitals around the world. To do this, Abbott provided its newest blood test to TRACK-TBI for analysis, while being blinded throughout the study to which samples represented which subjects.

The study results looked at the new handheld blood test, which specifically measures two types of proteins – GFAP and UCH-L1 – that are released from the brain and into the blood when the brain is injured. Or, as Beth McQuiston, M.D., R.D., neurologist and medical director in diagnostics at Abbott puts it, “We have blood tests used in the hospital to detect injury throughout the body. For example, your heart, kidney and liver. Yet, we don’t have a blood test to detect injury in the brain. This research shows that a blood test has the potential to help doctors evaluate and treat patients suspected of brain injury quickly and accurately to get them back to better health. Our blood test in development could be the first point-of-care blood test for assessing concussions.”

Dr. Manley adds, “This study demonstrates that these blood-based biomarkers are more sensitive at detecting brain injury than a CT scan. Even when we found that the CT scan was negative, the research found that these blood proteins levels were elevated above both the healthy and orthopedic controls.” As part of the study, the diagnosis of brain injury was by an MRI scan. Importantly, even when the MRI scan was negative, this protein was elevated more than it was in the controls – suggesting that similar to CT scans, it may be more sensitive than MRI imaging. “And this research suggests,” says Manley, “that proteins have the potential to improve our ability to triage patients with traumatic brain injury.”

While there are still many research milestones for TRACK-TBI, the detection of TBI and identification of patients who need brain injury treatment and care could be a significant game changer – principally for emergency situations. Using only a few drops of blood, assessment of the brain could literally, change lives in a matter of minutes.

https://www.forbes.com/sites/nicolefisher/2019/08/24/study-finds-new-blood-test-could-help-detect-brain-injury-in-minutes/#3ea8cc4e3ac8


CTE is a neurodegenerative disease that has been associated with a history of repetitive head impacts, including those that may or may not be associated with concussion symptoms in American football players. The image is in the public domain.

Summary: PET imaging of former NFL players who exhibited cognitive decline and psychiatric symptoms linked to CTE showed higher levels of tau in areas of the brain associated with the neurodegenerative disease. Using an experimental positron emission tomography (PET) scan, researchers have found elevated amounts of abnormal tau protein in brain regions affected by chronic traumatic encephalopathy (CTE) in a small group of living former National Football League (NFL) players with cognitive, mood and behavior symptoms. The study was published online in the New England Journal of Medicine.

Source: Boston University School of Medicine

The researchers also found the more years of tackle football played (across all levels of play), the higher the tau protein levels detected by the PET scan. However, there was no relationship between the tau PET levels and cognitive test performance or severity of mood and behavior symptoms.

“The results of this study provide initial support for the flortaucipir PET scan to detect abnormal tau from CTE during life. However, we’re not there yet,” cautioned corresponding author Robert Stern, PhD, professor of neurology, neurosurgery and anatomy and neurobiology at Boston University School of Medicine (BUSM). “These results do not mean that we can now diagnose CTE during life or that this experimental test is ready for use in the clinic.”

CTE is a neurodegenerative disease that has been associated with a history of repetitive head impacts, including those that may or may not be associated with concussion symptoms in American football players. At this time, CTE can only be diagnosed after death by a neuropathological examination, with the hallmark findings of the build-up of an abnormal form of tau protein in a specific pattern in the brain. Like Alzheimer’s disease (AD), CTE has been suggested to be associated with a progressive loss of brain cells. In contrast to AD, the diagnosis of CTE is based in part on the pattern of tau deposition and a relative lack of amyloid plaques.

The study was conducted in Boston and Arizona by a multidisciplinary group of researchers from BUSM, Banner Alzheimer’s Institute, Mayo Clinic Arizona, Brigham and Women’s Hospital and Avid Radiopharmaceuticals. Experimental flortaucipir PET scans were used to assess tau deposition and FDA-approved florbetapir PET scans were used to assess amyloid plaque deposition in the brains of 26 living former NFL players with cognitive, mood, and behavior symptoms (ages 40-69) and a control group of 31 same-age men without symptoms or history of traumatic brain injury. Results showed that the tau PET levels were significantly higher in the former NFL group than in the controls, and the tau was seen in the areas of the brain which have been shown to be affected in post-mortem cases of neuropathologically diagnosed CTE.

Interestingly, the former player and control groups did not differ in their amyloid PET measurements. Indeed, only one former player had amyloid PET measurements comparable to those seen in Alzheimer’s disease.

“Our findings suggest that mild cognitive, emotional, and behavioral symptoms observed in athletes with a history of repetitive impacts are not attributable to AD, and they provide a foundation for additional research studies to advance the scientific understanding, diagnosis, treatment, and prevention of CTE in living persons, said co-author, Eric Reiman, MD, Executive Director of Banner Alzheimer’s Institute in Phoenix, Arizona. “More research is needed to draw firm conclusions, and contact sports athletes, their families, and other stakeholders are waiting.

With support from NIH, the authors are working with additional researchers to conduct a longitudinal study called the DIAGNOSE CTE Research Project in former NFL players, former college football players, and persons without a history of contact sports play to help address these and other important questions. Initial results of that study are expected in early 2020.

https://neurosciencenews.com/pet-imaging-tau-nfl-11061/


The research has presented strong evidence that Parkinson’s disease begins in the gastrointestinal tract and spreads via the vagus nerve to the brain. Many patients have also suffered from gastrointestinal symptoms before the Parkinson’s diagnosis is made. The image is for illustrative purposes only.

A major epidemiological registry-based study from Aarhus University and Aarhus University Hospital indicates that Parkinson’s disease begins in the gastrointestinal tract; the study is the largest in the field so far.

The chronic neurodegenerative Parkinson’s disease affects an increasing number of people. However, scientists still do not know why some people develop Parkinson’s disease. Now researchers from Aarhus University and Aarhus University Hospital have taken an important step towards a better understanding of the disease.

New research indicates that Parkinson’s disease may begin in the gastrointestinal tract and spread through the vagus nerve to the brain.

“We have conducted a registry study of almost 15,000 patients who have had the vagus nerve in their stomach severed. Between approximately 1970-1995 this procedure was a very common method of ulcer treatment. If it really is correct that Parkinson’s starts in the gut and spreads through the vagus nerve, then these vagotomy patients should naturally be protected against developing Parkinson’s disease,” explains postdoc at Aarhus University Elisabeth Svensson on the hypothesis behind the study.

A hypothesis that turned out to be correct:

“Our study shows that patients who have had the the entire vagus nerve severed were protected against Parkinson’s disease. Their risk was halved after 20 years. However, patients who had only had a small part of the vagus nerve severed were not protected. This also fits the hypothesis that the disease process is strongly dependent on a fully or partially intact vagus nerve to be able to reach and affect the brain,” she says.

The research project has just been published in the internationally recognised journal Annals of Neurology.

The first clinical examination

The research has presented strong evidence that Parkinson’s disease begins in the gastrointestinal tract and spreads via the vagus nerve to the brain. Many patients have also suffered from gastrointestinal symptoms before the Parkinson’s diagnosis is made.

“Patients with Parkinson’s disease are often constipated many years before they receive the diagnosis, which may be an early marker of the link between neurologic and gastroenterologic pathology related to the vagus nerve ,” says Elisabeth Svensson.

Previous hypotheses about the relationship between Parkinson’s and the vagus nerve have led to animal studies and cell studies in the field. However, the current study is the first and largest epidemiological study in humans.

The research project is an important piece of the puzzle in terms of the causes of the disease. In the future the researchers expect to be able to use the new knowledge to identify risk factors for Parkinson’s disease and thus prevent the disease.

“Now that we have found an association between the vagus nerve and the development of Parkinson’s disease, it is important to carry out research into the factors that may trigger this neurological degeneration, so that we can prevent the development of the disease. To be able to do this will naturally be a major breakthrough,” says Elisabeth Svensson.

https://neurosciencenews.com/parkinsons-gastrointestinal-tract-neurology-2150/

Having a parent with Alzheimer’s disease has been known to raise a person’s risk of developing the disease, but new research published in Neurology suggests that having second- and third-degree relatives who have had Alzheimer’s may also increase risk.

“Family history is an important indicator of risk for Alzheimer’s disease, but most research focuses on dementia in immediate family members, so our study sought to look at the bigger family picture,” said Lisa A. Cannon-Albright, PhD, University of Utah School of Medicine, Salt Lake City, Utah. “We found that having a broader view of family history may help better predict risk. These results potentially could lead to better diagnoses and help patients and their families in making health-related decisions.”

For the study, researchers looked at the Utah Population Database, which includes the genealogy of Utah pioneers from the 1800s and their descendants up until modern day. The database is linked to Utah death certificates, which show causes of death, and in a majority of cases, contributing causes of death.

In that database, researchers analysed data from over 270,800 people who had at least 3 generations of genealogy connected to the original Utah pioneers including genealogy data for both parents, all 4 grandparents, and at least 6 of 8 great-grandparents. Of those, 4,436 have a death certificate that indicates Alzheimer’s disease as a cause of death.

Results showed that people with 1 first-degree relative with Alzheimer’s disease (18,494 people) had a 73% increased risk of developing the disease. Of this group of people, 590 developed Alzheimer’s disease; the researchers would have expected this group to have 341 cases.

People with 2 first-degree relatives were 4 times more likely to develop the disease; those with 3 were 2.5 times more likely; and those with 4 were nearly 15 times more likely to develop Alzheimer’s disease.

Of the 21 people in the study with 4 first-degree relatives with Alzheimer’s, 6 had the disease. The researchers would have expected only 0.4 people to develop the disease.

Those with 1 first-degree relative and 1 second-degree relative had a 21 times greater risk. Examples of this would be a parent and one grandparent with the disease, or a parent and one aunt or uncle. There were 25 people in this category in the study; 4 of them had the disease when researchers would have expected 0.2 cases.

Those who had only third-degree relatives, and 3 such relatives, with Alzheimer’s disease had a 43% greater risk of developing the disease. An example of this would be two great-grandparents with the disease, along with one great uncle, but no parents or grandparents with the disease. Of the 5,320 people in this category, 148 people had the disease when researchers would have expected 103.

“More and more, people are increasingly seeking an estimate of their own genetic risk for Alzheimer’s disease,” said Dr. Cannon-Albright. “Our findings indicate the importance of clinicians taking a person’s full family history that extends beyond their immediate family members.”

She noted that among all of the study participants, 3% had a family history that doubled their risk of Alzheimer’s disease, and a little over one-half of a percent had a family history that increased their risk by ≥3 times that of a person without a family history of the disease.

Limitations of the study include that not all individuals dying from Alzheimer’s disease may have had a death certificate listing it as cause of death. Dr. Cannon-Albright said death certificates are known to underestimate the prevalence of the disease.

“There are still many unknowns about why a person develops Alzheimer’s disease,” she said. “A family history of the disease is not the only possible cause. There may be environmental causes, or both. There is still much more research needed before we can give people a more accurate prediction of their risk of the disease.”

Reference:
https://n.neurology.org/content/early/2019/03/13/WNL.0000000000007231

https://dgnews.docguide.com/having-great-grandparents-cousins-alzheimer-s-linked-higher-risk?overlay=2&nl_ref=newsletter&pk_campaign=newsletter&nl_eventid=20119


A normal brain of a 70-year-old (left slice), compared with the brain of a 70-year-old with Alzheimer’s disease.Credit: Jessica Wilson/Science Photo Library

Neuroscientists have amassed more evidence for the hypothesis that sticky proteins that are a hallmark of neurodegenerative diseases can be transferred between people under particular conditions — and cause new damage in a recipient’s brain.

They stress that their research does not suggest that disorders such as Alzheimer’s disease are contagious, but it does raise concern that certain medical and surgical procedures pose a risk of transmitting such proteins between humans, which might lead to brain disease decades later.

“The risk may turn out to be minor — but it needs to be investigated urgently,” says John Collinge, a neurologist at University College London who led the research, which is published in Nature1 on 13 December.

The work follows up on a provocative study published by Collinge’s team in 20152. The researchers discovered extensive deposits of a protein called amyloid-beta during post-mortem studies of the brains of four people in the United Kingdom. They had been treated for short stature during childhood with growth-hormone preparations derived from the pituitary glands of thousands of donors after death.

The recipients had died in middle-age of a rare but deadly neurodegenerative condition called Creutzfeldt-Jakob disease (CJD), caused by the presence in some of the growth-hormone preparations of an infectious, misfolded protein — or prion — that causes CJD. But pathologists hadn’t expected to see the amyloid build up at such an early age. Collinge and his colleagues suggested that small amounts of amyloid-beta had also been transferred from the growth-hormone samples, and had caused, or ‘seeded’, the characteristic amyloid plaques.

Seeds of trouble
Amyloid plaques in blood vessels in the brain are a hallmark of a disease called cerebral amyloid angiopathy (CAA) and they cause local bleeding. In Alzheimer’s disease, however, amyloid plaques are usually accompanied by another protein called tau — and the researchers worry that this might also be transmitted in the same way. But this was not the case in the brains of the four affected CJD patients, which instead had the hallmarks of CAA.

The team has now more directly tested the hypothesis that these proteins could be transmitted between humans through contaminated biological preparations. Britain stopped the cadaver-derived growth hormone treatment in 1985 and replaced it with a treatment that uses synthetic growth hormone. But Collinge’s team was able to locate old batches of the growth-hormone preparation stored as powder for decades at room temperature in laboratories at Porton Down, a national public-health research complex in southern England.

When the researchers analysed the samples, their suspicions were confirmed: they found that some of the batches contained substantial levels of amyloid-beta and tau proteins.

Mouse tests
To test whether the amyloid-beta in these batches could cause the amyloid pathology, they injected samples directly into the brains of young mice genetically engineered to be susceptible to amyloid pathology. By mid-life, the mice had developed extensive amyloid plaques and CAA. Control mice that received either no treatment or treatment with synthetic growth hormone didn’t have amyloid build up.

The scientists are now checking in separate mouse experiments whether the same is true for the tau protein.

“It’s an important study, though the results are very expected,” says Mathias Jucker at the Hertie Institute for Clinical Brain Research in Tubingen, Germany. Jucker demonstrated in 2006 that amyloid-beta extracted from human brain could initiate CAA and plaques in the brains of mice3. Many other mouse studies have also since confirmed this.

Surgical implications
That the transmissibility of the amyloid-beta could be preserved after so many decades underlines the need for caution, says Jucker. The sticky amyloid clings tightly to materials used in surgical instruments, resisting standard decontamination methods4. But Jucker also notes that, because degenerative diseases take a long time to develop, the danger of any transfer may be most relevant in the case of childhood surgery where instruments have also been used on old people.

So far, epidemiologists have not been able to assess whether a history of surgery increases the risk of developing a neurodegenerative disease in later life — because medical databases tend not to include this type of data.

But epidemiologist Roy Anderson at Imperial College London says researchers are taking the possibility seriously. Major population cohort studies, such as the US Framingham Heart Study, are starting to collect information about participants’ past surgical procedures, along with other medical data.

The 2015 revelation prompted pathologists around the world to reexamine their own cases of people who had been treated with similar growth-hormone preparations — as well as people who had acquired CJD after brain surgery that had involved the use of contaminated donor brain membranes as repair patches. Many of the archived brain specimens, they discovered, were full of aberrant amyloid plaques5,6,7. One study showed that some batches of growth-hormone preparation used in France in the 1970s and 1980s were contaminated with amyloid-beta and tau — and that tau was also present in three of their 24 patients.8

Collinge says he applied unsuccessfully for a grant to develop decontamination techniques for surgical instruments after his 2015 paper came out. “We raised an important public-health question, and it is frustrating that it has not yet been addressed.” But he notes that an actual risk from neurosurgery has not yet been established.

https://www.nature.com/articles/d41586-018-07735-w?utm_source=fbk_nnc&utm_medium=social&utm_campaign=naturenews&sf204283628=1

Thank to Kebmodee for bringing this to the It’s Interesting community.

SS39069

By Alan Mozes

People with attention-deficit/hyperactivity disorder (ADHD) may be more than twice as likely to develop an early onset form of Parkinson’s, new research warns.

What’s more, among “those ADHD patients who had a record of being treated with amphetamine-like drugs — especially Ritalin [methylphenidate] — the risk dramatically increased, to between eight- to nine-fold,” said senior study author Glen Hanson.

But his team did not prove that ADHD or its medications actually caused Parkinson’s risk to rise, and one ADHD expert noted that the absolute risk of developing Parkinson’s remains very small.

For the study, researchers analyzed nearly 200,000 Utah residents. All had been born between 1950 and 1992, with Parkinson’s onset tracked up until the age of 60.

Prior to any Parkinson’s diagnosis, roughly 32,000 had been diagnosed with ADHD.

Hanson, a professor of pharmacology and toxicology at the University of Utah, said that ADHD patients were found to be “2.4 times more likely to develop Parkinson’s disease-like disorders prior to the age of 50 to 60 years,” compared with those with no history of ADHD. That finding held up even after accounting for a number of influential factors, including smoking, drug and alcohol abuse, and other psychiatric disorders.

“Although we cannot accurately say how much time elapsed between ADHD and [a] Parkinson’s-like disorder diagnosis, it was probably between 20 to 50 years,” he said.

As to what might explain the link, Hanson said that both ADHD and most forms of Parkinson’s source back to a “functional disorder of central nervous system dopamine pathways.”

In addition, Hanson said that “the drugs used to treat ADHD apparently work because of their profound effects on the activity of these dopamine pathways.” Theoretically, the treatment itself might trigger a metabolic disturbance, promoting dopamine pathway degeneration and, ultimately, Parkinson’s, he explained.

Still, Hanson pointed out that, for now, “we are not able to determine if the increased risk associated with stimulant use is due to the presence of the drug or the severity of the ADHD,” given that those treated with ADHD drugs tend to have more severe forms of the disorder.

And while demonstrating “a very strong association” between ADHD and Parkinson’s risk, the findings are preliminary, the study authors added.

Also, the absolute risk of developing Parkinson’s remained low, even in the most pessimistic scenario.

For example, the findings suggest that the risk of developing early onset Parkinson’s before the age of 50 would be eight or nine people out of every 100,000 with ADHD. This compares with one or two out of every 100,000 among those with no history of ADHD, the researchers said.

But the scientists noted that the results should raise eyebrows, because Parkinson’s primarily strikes people over the age of 60. Given the age range of those tracked so far in the study, Hanson said that his team was not yet able to ascertain Parkinson’s risk among ADHD patients after the age of 60.

Hanson also pointed out that because ADHD was only first diagnosed in the 1960s, only about 1.5 percent of the people in the study had an ADHD diagnosis, despite current estimates that peg ADHD prevalence at 10 percent. That suggests that the current findings may underestimate the scope of the problem.

“Clearly, there are some critical questions left to be answered concerning what is the full impact of this increased risk,” Hanson said.

Dr. Andrew Adesman is chief of developmental and behavioral pediatrics at Cohen Children’s Medical Center of New York with Northwell Health in New York City. He was not involved with the study and said the findings “surprised” him.

But, “we need to keep in mind that this study needs to be replicated and that the incidence of these conditions was very low, even among those with ADHD,” Adesman said. “The reality is that this would not affect 99.99 percent of individuals with ADHD.”

Meanwhile, Adesman said, “given that this study needs to be replicated, given that it is unclear whether ADHD medications further increase the risks of Parkinson’s, and given the very low risk in an absolute sense, I believe individuals with ADHD should not be hesitant to pursue or continue medical treatment for their ADHD.”

The report was published online Sept. 12 in the journal Neuropsychopharmacology.

Glen Hanson, DDS, Ph.D., vice dean and professor, pharmacology, School of Dentistry, University of Utah, Salt Lake City; Andrew Adesman, M.D., chief, developmental and behavioral pediatrics, Steven & Alexandra Cohen Children’s Medical Center of New York, Northwell Health, New York City; Sept. 12, 2018, Neuropsychopharmacology, online

https://consumer.healthday.com/cognitive-health-information-26/parkinson-s-news-526/adhd-tied-to-raised-risk-of-early-parkinson-s-737637.html