Some brain-boosting supplements contain an unapproved drug that could harm users, study warns8

Some brain-boosting supplements contain an unapproved drug that could harm users, study warns

By ELIZABETH COONEY @cooney_liz

NOVEMBER 25, 2019

The FDA has sent warning letters to companies including Pure Nootropics for selling piracetam as a dietary supplement.FDA

Promising to lift brain fog or improve memory, brain-boosting supplements have joined sexual-enhancement and weight-loss remedies in the lightly regulated world of dietary supplements. These products may be sold legally with broad-brush come-ons like these, as long as they don’t make specific claims about treating a disease — or contain actual drugs.

New research led by Dr. Pieter Cohen of Harvard Medical School documents five supplement brands for sale in the U.S. that contain various amounts of piracetam, a drug prescribed in European countries for cognitive impairment in dementia but not approved in the U.S. 

The Food and Drug Administration doesn’t allow piracetam to be sold as a dietary supplement and has issued warning letters in the past to other companies marketing supplements that contain it. Though the drug is approved in Europe, evidence for using piracetam to improve cognition was “inadequate,” a Cochrane Review analyzing 24 studies that enrolled more than 11,000 patients concluded in 2012.
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Herpes Virus Variant Linked to MS Onset

NEWS   Nov 27, 2019 | Original story from Karolinska Institutet

A stained histological slide of the human herpes virus-6 showing infected cells, with inclusion bodies in both the nucleus and the cytoplasm.8

Researchers at Karolinska Institutet have developed a new method to separate between two different types of a common herpes virus (HHV-6) that has been linked to multiple sclerosis. By analyzing antibodies in the blood against the most divergent proteins of herpesvirus 6A and 6B, the researchers were able to show that MS-patients carry the herpesvirus 6A to a greater extent than healthy individuals. The findings, published in Frontiers in Immunology, point to a role for HHV-6A in the development of MS.

Multiple sclerosis, MS, is an autoimmune disease that affects the central nervous system. The cause of the disease is unclear, but one plausible explanation is a virus tricks the immune system to attack the body's own tissue. Human Herpesvirus 6 (HHV-6) has previously been associated with MS, but in those studies it wasn't possible to distinguish between 6A and 6B. Through virus isolation from ill individuals, researchers have been able to show that HHV-6B can cause mild conditions such as roseola in children, but it has been unclear if HHV-6A is the cause of any disease.

According to estimates, as many as 80 percent of all children are infected with the HHV-6 virus before 2 years of age, and many also carry protection in the form of antibodies against this particular virus for the rest of their lives. But since it hasn't been possible to tell the two variants apart post-infection, it has been difficult to say whether HHV-6A or B is a risk factor for MS.

In this study, however, the researchers were able to distinguish between the A and B virus by analyzing antibodies in the blood against the proteins--immediate early protein 1A and 1B (IE1A and IE1B)--that diverge the most between the two viruses.

"This is a big breakthrough for both the MS and herpes virus research," says Anna Fogdell-Hahn, associate professor at the Department of Clinical Neuroscience at Karolinska Institutet and one of the study's senior authors. "For one, it supports the theory that HHV-6A could be a contributing factor to the development of MS. On top of that, we are now able, with this new method, to find out how common these two different types of HHV-6 are, something we haven't been able to do previously."

The researchers compared antibody levels in blood samples of some 8,700 MS-patients against more than 7,200 healthy people whose gender, date of birth, date of blood sample and other factors matched those with MS. They concluded that people with MS had a 55 percent higher risk of carrying antibodies against the HHV-6A protein than the control group. In a sub-group of almost 500 people, whose blood samples were drawn before the onset of the disease, the risk of developing MS in the future was more than doubled if they had a 6A viral infection. The younger the people were when the virus was first discovered in the blood, the higher the risk was of developing MS in the future. HHV-6B, on the other hand, was not positively associated with MS. Instead MS-patients had lower levels of antibodies toward IE1B than those without MS.

Antibodies toward Epstein-Barr virus (EBV), another herpes virus that is also associated with MS, were analyzed with the same method and the researchers were able to show that individuals affected with both viruses had an even greater risk of MS. This indicates that several virus infections could be acting jointly to increase the risk of MS.

"Both HHV-6A and 6B can infect our braincells, but they do it in slightly different ways. Therefore, it is now interesting to go forward and attempt to map out exactly how the viruses could affect the onset of MS," says Anna Fogdell-Hahn.

Reference: Engdahl, E., Gustafsson, Brain Organoids Offer Clues to Neuron-killing Virus

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Non-invasive Sound Energy Therapy Relieves Parkinson's Tremors

NEWS   Nov 27, 2019 | Original story from the Radiological Society of North America

Credit: Federico Bruno/RSNA

 Read Time: 3 min

A procedure that applies pulses of focused ultrasound to the brain is safe and effective for reducing tremors and improving quality of life in people with essential tremor (ET) or Parkinson's disease (PD) tremor, according to a new study being presented next week at the annual meeting of the Radiological Society of North America (RSNA).

Tremors are rhythmic, involuntary muscle movements that cause shaking in one or more parts of the body, usually in the hands. They are characteristic of movement disorders like ET and PD, two progressive conditions that affect millions of people worldwide.

Previous treatment options for reducing tremors in patients who have not responded to medical therapy include deep brain stimulation, a surgical procedure that involves implanting a small electrode in the brain connected to a pulse generator that is implanted in the chest like a pacemaker.

A more recently available option is magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy, an incisionless interventional radiology procedure in which focused beams of sound energy are used to heat and destroy a small part of a structure in the brain called the thalamus. The procedure gives relief to the opposite side of the body, meaning that treatment to the right side of the brain would relieve tremors on the left side of the body, and vice versa.

As a minimally invasive approach, focused ultrasound has advantages over deep brain stimulation, including a reduced risk of complications from bleeding and infections, according to study lead author Federico Bruno, M.D., a radiologist in the Department of Biotechnological and Applied Clinical Sciences at the University of L'Aquila in L'Aquila, Italy.

"Another advantage is the immediate effect this treatment provides, unlike deep brain stimulation which requires a break-in period for the electrostimulation," he said. "Additionally, treatment with MRgFUS requires shorter hospitalization and is a fairly well-tolerated procedure even by more fragile patients."

For the new study, Bruno and colleagues enrolled 39 patients, average age 64.5 years, with disabling tremors that had not responded to treatment. The people in the study group, including 18 with ET and 21 with PD, had experienced symptoms for an average of more than 10 years.

The researchers evaluated the patients for tremor severity and quality of life before MRgFUS thalamotomy, immediately after treatment and over the course of the ensuing year.

They found that 37 of 39 patients, or 95%, had substantial and immediate reduction of tremor. These reductions in tremor were sustained in follow-up evaluations. Quality of life evaluation showed substantial improvement in both the ET and PD groups.

"The study we present reports our experience of over a year in the treatment of tremor by thalamotomy with focused ultrasound," Bruno said. "It is worth noting that we had a high number of patients with Parkinson's disease in our series, compared to previously published data, where the procedure was used mainly in the treatment of essential tremor patients."

Currently, MRgFUS thalamotomy is only available at a limited number of sites worldwide, Bruno said, but may become more widespread as research findings supporting its use are published. Improvements in neuroimaging techniques that allow for greater precision and detail in planning, implementation and monitoring over time of the treatment should also expand its availability.

"The clinical application of this technique for neurological diseases is an absolute novelty—the clinical use was approved by the FDA less than three years ago," Bruno said. "Few patients know of this treatment option so far, and there are not many specialized centers equipped with the required technology."

Future research in this area includes the possibility of treating both sides of the thalamus. MRgFUS is also being explored in areas beyond movement disorders, Bruno said. Several preclinical studies and clinical trials are looking at the technique for the treatment of other neurological conditions like neuropathic pain, epilepsy and obsessive-compulsive disorders, as well as for treatment of brain tumors.

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Plant Power: UK Scientists Are Hunting for the Medicines on Our Doorstep

NEWS   Nov 26, 2019 | By Molly Campbell, Science Writer, Technology Networks

Molly Campbell

Science Writer

 @mollyrcampbell

 Read Time: 2 min

The therapeutic potential of botanic-derived compounds is well established, and an array of pathological conditions have been treated using such "natural products".1

Take atropine, for example. An anticholinergic compound, atropine is produced by certain members of the Solanaceae family of plants and has been utilized in medicine to treat the symptoms of bradycardia (slow heart rate).

If you've ever experienced symptoms of great pain, your doctor may have advised you to take codeine, an alkaloid drug produced by the opium poppy, Papaver somniferum var. album. A precursor of the painkiller aspirin was also originally found in willow bark.

Credit: Pixabay.

The twentieth century saw major advancements in scientific technologies and processes that enabled the production of thousands of chemically synthesized drugs. Nonetheless, plant biologicals remain very much integral to modern medicine – so much so that a team of researchers from the Earlham Institute (EI) are exploring the genetics of UK wildflowers to discover medicines that, quite literally, may be on our doorstep.

The scientists, led by Nicola Patron, Synthetic Biology Group Leader at EI, will utilize biochemical approaches to identify chemicals that the plants are producing. They will then sequence the genomes of the plants to pinpoint which genes are responsible for the production of the molecules. Their hopes are that this information will aid our understanding of how plants are capable of producing complex molecules, and support drug discovery and biomanufacturing endeavors.

The research is contributing to the UK arm of the Darwin Tree of Life Project, which is a subcomponent of the Earth BioGenome Project, a global effort to sequence the DNA of all known species of animals, plants and fungi on the planet.

Patron says, "Understanding how species evolve the ability to make new molecules is a major goal in evolutionary biology and it can also help us to identify and make new molecules for use in health and industry." She continues: "By linking data about the chemicals being made and the genes being expressed, we will be able to identify unknown chemical diversity as well as the genes used for their biosynthesis.”

The researchers will start their quest with the daisy family (Asteraceae). These species have been a component of traditional medicine and previous research has hinted to the physiological mechanisms underpinning their "healing" qualities. It is estimated that there are approximately 900 species of daisy in the UK.

Credit: Pixabay.

Neil Hall, Professor and Director of the EI, says "This work is a great example of how sequencing genomes of wild species could lead to entirely new ways of harnessing nature for the public good. My hope is that in the next ten years we will have sequenced the vast majority of plant genomes, unlocking a treasure trove of pathways that make compounds which can be used in medicine and biotech.”

Reference: Thomford et al. 2018. Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery. International Journal of of Molecular Sciences. DOI: 10.3390/ijms19061578.

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New Discovery in Bacteria Epigenome Could Lead to Treatments for Dangerous Infections.

New Discovery in Bacteria Epigenome Could Lead to Treatments for Dangerous Infections.

A process called sporulation that helps the dangerous bacterium Clostridium difficile (C. difficile) to survive inhospitable conditions and spread is regulated by epigenetics, factors that affect gene expression beyond the DNA genetic code, researchers at the Icahn School of Medicine at Mount Sinai report. This is the first discovery that epigenetics regulates sporulation in any bacteria. Their research opens a new window to developing treatments for this devastating infection.

C. difficile infects nearly half a million people each year, causing severe diarrhea and killing just under 10 percent of those over 65 who contract it. Spores of the bacteria, which are spread through feces, are extremely resilient and can survive outside the body for weeks or months, infecting individuals who come in contact with contaminated surfaces.

Since the infection is so common and devastating, the C. difficile genome has been well studied, but Gang Fang, Ph.D., Associate Professor of Genetics and Genomic Sciences at Mount Sinai’s Icahn Institute for Data Science and Genomic Technology and senior author of the study, says he and his colleagues took a different approach in their research. “We wanted to study beyond the genetic code of the bacteria and look at what chemical modifications were being made to the genome,” said Fang. While these epigenetic chemical modifications, called methylation, do not alter the sequence of a gene, they can modify a particular gene’s activity to render it more or less active, which has profound impacts on the organism’s function. 

Fang’s team pioneered the use of third-generation DNA sequencing to map epigenetic factors in bacteria in 2012 and began studying C. difficile epigenetics in 2015. First, the team isolated C. difficile from fecal samples of 36 patients in the intensive care unit (ICU) at Mount Sinai Hospital who had been infected with it. They analyzed the samples and found one particular epigenetic pattern that was highly conserved throughout all the samples. Next, they checked about 300 C. difficile genomes from GenBank, a databank of genetic sequences run by the National Institutes of Health, and found that all shared the same gene responsible for the epigenetic pattern found in the ICU patients. 

Suspecting this epigenetic pattern was playing a crucial role in the function of the bacteria, Fang’s team collaborated on two further studies of C. difficile sporulation and mice infected with C. difficile, with the lab of Aimee Shen, Ph.D., Associate Professor of Molecular Biology & Microbiology at Tufts University Medical School and a co-senior author of the study, and with the lab of Rita Tamayo, PhD, Associate Professor of Microbiology and Immunology at the University of North Carolina, Chapel Hill. In one study with mice, the researchers found that when they inhibited the gene responsible for the epigenetic pattern, as much as 100 times less bacteria was present after 6 days compared to unaltered bacteria. 

Fang says the findings in these studies underscore the significance of epigenetics in the study of bacteria and drug development for infection.

In addition to offering new epigenetic insights into the study of C. difficile and possible targets for drug development, Fang hopes this research will encourage further studies of the epigenetic characteristics of bacteria. “This is just the beginning of our understanding of epigenetic regulation in bacteria; there are still so many questions yet to be answered,” said Fang. “We hope this exciting discovery will encourage further interdisciplinary collaborations to investigate epigenetics of bacteria and how we can use these new insights to develop life-saving treatments for infection.”

https://www.nature.com/articles/s41564-019-0613-4

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High Antibiotic Use Linked to Parkinson's Disease

NEWS   Nov 25, 2019 | Original story from the University of Helsinki

Credit: Pixabay

 Read Time: 2 min

Higher exposure to commonly used oral antibiotics is linked to an increased risk of Parkinson's disease according to a recently published study by researchers from the Helsinki University Hospital, Finland.

The strongest associations were found for broad-spectrum antibiotics and those that act against anaerobic bacteria and fungi. The timing of antibiotic exposure also seemed to matter.

The study suggests that excessive use of certain antibiotics can predispose to Parkinson's disease with a delay of up to 10 to 15 years. This connection may be explained by their disruptive effects on the gut microbial ecosystem.

“The link between antibiotic exposure and Parkinson's disease fits the current view that in a significant proportion of patients the pathology of Parkinson's may originate in the gut, possibly related to microbial changes, years before the onset of typical Parkinson motor symptoms such as slowness, muscle stiffness and shaking of the extremities. It was known that the bacterial composition of the intestine in Parkinson's patients is abnormal, but the cause is unclear. Our results suggest that some commonly used antibiotics, which are known to strongly influence the gut microbiota, could be a predisposing factor," says research team leader, neurologist Filip Scheperjans MD, Ph.D. from the Department of Neurology of Helsinki University Hospital.

In the gut, pathological changes typical of Parkinson's disease have been observed up to 20 years before diagnosis. Constipation, irritable bowel syndrome and inflammatory bowel disease have been associated with a higher risk of developing Parkinson's disease. Exposure to antibiotics has been shown to cause changes in the gut microbiome and their use is associated with an increased risk of several diseases, such as psychiatric disorders and Crohn's disease. However, these diseases or increased susceptibility to infection do not explain the now observed relationship between antibiotics and Parkinson's.

“The discovery may also have implications for antibiotic prescribing practices in the future. In addition to the problem of antibiotic resistance, antimicrobial prescribing should also take into account their potentially long-lasting effects on the gut microbiome and the development of certain diseases,” says Scheperjans.

The possible association of antibiotic exposure with Parkinson's disease was investigated in a case-control study using data extracted from national registries. The study compared antibiotic exposure during the years 1998-2014 in 13,976 Parkinson's disease patients and compared it with 40,697 non-affected persons matched for the age, sex and place of residence.

Antibiotic exposure was examined over three different time periods: 1-5, 5-10, and 10-15 years prior to the index date, based on oral antibiotic purchase data. Exposure was classified based on number of purchased courses. Exposure was also examined by classifying antibiotics according to their chemical structure, antimicrobial spectrum, and mechanism of action.

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Reference

Mertsalmi et al. (2019) Antibiotic exposure and risk of Parkinson's disease in Finland: A nationwide case‐control study. Movement Disorders. DOI: https://doi.org/10.1002/mds.27924

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