Tag: The Conversation

Categories : Neurodegenerative DiseasesTags :

Epstein-Barr Virus: How does a Common Infection Trick the Immune System into Attacking the Brain in People with MS?

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An electron micrograph showing three Epstein-Barr virus (EBV) particles colourised red-orange. Credit: NIAID

Olivia Thomas, Karolinska Institutet; Graham Taylor, University of Birmingham, and Jill Brooks, University of Birmingham

Almost 3 million people worldwide have multiple sclerosis (MS) – an autoimmune disease caused by the immune system mistakenly attacking the brain and central nervous system.

While treatments for MS have improved over the years, there’s still no cure. This is largely because researchers still don’t fully understand what goes wrong in the immune system to cause MS. But our latest research has revealed new insights into the way certain immune cells behave in people with MS. This discovery brings us closer to understanding why some people get MS – and may also be a crucial step in developing better treatments and even cures.

Although the causes of MS aren’t fully understood, we know that genetics, lifestyle and environment factors can all influence MS risk. But the biggest risk factor for developing MS appears to be a common virus called Epstein-Barr virus (EBV).

EBV typically infects people during childhood without causing any symptoms – so most early infections go unnoticed. But if the infection occurs during adolescence, it may cause glandular fever (infectious mononucleosis) which, although debilitating in the short-term, usually has no long-term effects.

Most viral infections are rapidly cleared by the body’s immune system, but EBV is cleverer than most viruses. Although the immune system controls the infection, it is unable to completely eradicate the virus as it hides inside a type of immune cell called a B cell (which normally produce antibodies that bind to and destroy invading viruses or bacteria). Once you’re infected with EBV you carry it for life – although for most people this causes no problems.

By adulthood about 95% of people are infected with EBV, but in people with MS nearly 100% are infected. Large epidemiological studies have shown that EBV infection increases the risk of developing MS over 30-fold. For people who have had glandular fever the risk is even higher. Research has also shown that in people with MS, EBV infection occurs before the very earliest stages of disease.

Many researchers now believe being infected with EBV is more than a risk factor in MS – it’s essential.

But how does EBV cause MS – and why does a common virus only cause MS in a few people? Several theories are currently being investigated.

One theory is that in some people the immune cells activated by EBV mistakenly attack parts of the brain and central nervous system. This process, called molecular mimicry, also occurs in other autoimmune diseases, such as Guillain-Barré syndrome. This could explain why drugs which prevent immune cells from entering the brain are shown to dramatically improve MS symptoms.

Research into EBV molecular mimicry in MS has mainly focused on the viral protein EBNA1. Without EBNA1 EBV cannot live in B cells, and MS patients have higher levels of antibodies towards EBNA1.

But EBV makes over 80 different proteins during its life cycle. In our latest work we investigated immune responses to these other viral proteins in people with MS.

Altered immunity

We compared the immune responses of 31 people with MS, 33 healthy people and 11 people who had recently recovered from glandular fever. We wanted to see if each group reacted to EBV infections differently.

We found that antibodies targeting EBNA1 and another viral protein called VCA were higher in people with MS compared to the other groups. People with MS were also more likely to have antibodies targeting several other viral proteins. This suggests EBV antibodies are more altered in MS than previously thought – but it isn’t certain whether these antibodies are fighting infection or if they have a role in MS disease.

Scanning electron micrograph of a T cell lymphocyte. Credit: NIH / NIAID

Antibodies aren’t the full story. Previous research has suggested another type of immune cell, called a T cell, may also play an important role as they’re found in high numbers in MS brain lesions. As such, we wanted to understand whether T cells which fight EBV were different in people with MS.

By analysing blood samples we found that, although EBV T cell numbers were similar in MS and healthy people, these cells behaved differently in people with MS. T cells from people with MS produced slightly higher amounts of an inflammatory substance called interleukin-2. The body normally produces this substance in response to injury or infection, but too much interleukin-2 can cause chronic disease.

We also looked at molecular mimicry, wondering whether EBV T-cells mistakenly target brain proteins rather than fighting the virus.

Surprisingly, we found that in both people with MS and healthy people, their EBV T cells reacted to multiple proteins found in the brain. Notably, most people had EBV T cells that targeted a protein called myelin oligodendrocyte glycoprotein, or Mog, which surrounds the nerves.

Looking at one person with MS in more detail, we found individual T cells that directly recognised both EBNA1 and Mog. This means that, rather than just fighting infection, some EBV T cells could also target nerve cells in the brain.

This widespread misdirection between EBV T cells and the brain goes some way to suggest how infection with this common virus can lead to MS. But its presence in healthy people is slightly confusing. One possible explanation could be that EBV T cells are better able to cross the blood-brain barrier (a tight-knit lining of cells that protect the brain) in people with MS. This idea is something we’re keen to explore in future research.

While there’s still much we don’t know about these misdirected EBV T cells in the brain, our latest findings provide fresh evidence for researchers and hopefully will lead to the development of new, targeted treatments for MS.

Olivia Thomas, Assistant Professor, Department of Clinical Neuroscience, Karolinska Institutet; Graham Taylor, Associate Professor in Viral and Tumour Immunology, University of Birmingham, and Jill Brooks, Research Fellow, Institute of Cancer and Genomic Sciences, University of Birmingham

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Categories : Mental Health NeurologyTags :

Two Reasons I’m Sceptical About Psychedelic Science

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Photo by Marek Piwnicki

Michiel van Elk, Leiden University

Since I was young, I have been intrigued by altered states of consciousness, such as out-of-body experiences, paranormal phenomena and religious visions. I studied psychology and neuroscience to gain a better understanding of how these experiences come about. And in my scientific career, I have focused on the question of why some people are more prone to having these experiences than others.

Naturally, when I came across psychedelic science a couple of years ago, this field also sparked my academic interest. Here was an opportunity to study people who had a psychedelic experience and who claimed to have had a glimpse of ultimate reality. I started to research psychedelic experiences at Leiden University and founded the PRSM lab – a group of scientists from different academic backgrounds who study psychedelic, religious, spiritual and mystical experiences.

Initially, I was enthusiastic about the mind-transforming potential of psychedelics. These substances, when administered correctly, appear to be capable of enhancing people’s mental and physical wellbeing. They also increase feelings of connectedness to and concern for the environment.

Psychedelic therapy appeared to offer great potential for treating a wide variety of disorders, including depression, anxiety, addiction and post-traumatic stress disorder. This enthusiasm about the potentially transformative effects of psychedelics was reflected in positive media attention on this topic over the past few years. Michael Pollan, an American author and journalist, has brought psychedelics to an audience of millions with his book and Netflix documentary.

However, my initial optimism about psychedelics and their potential has changed into scepticism about the science behind much of the media hype. This is due to a closer scrutiny of the empirical evidence. Yes, at face value it seems as if psychedelic therapy can cure mental disease. But on closer inspection, the story is not that straightforward.

The main reason? The empirical evidence for the efficacy of and the working mechanisms underlying psychedelic therapy is far from clear.

Two issues

I wrote a critical review paper with my colleague Eiko Fried in which we listed the problems with the current clinical trials on psychedelic therapy. The main concern is called the “breaking blind problem”. In psychedelic studies, patients easily figure out if they have been randomly assigned to the psychedelic or the placebo group, simply because of the profound mind-altering effects of psychedelic substances.

This breaking-of-the-blind can actually result in placebo effect in patients in the psychedelic group: they finally get the treatment they’d been hoping for and they start feeling better. But it can also result in frustration and disappointment in patients assigned to the control group. They were hoping to get a miracle cure but now find out they will have to spend six hours on a placebo pill with their therapist.

As a consequence, any difference in therapeutic outcomes between the psychedelic and the placebo group is largely driven by these placebo and nocebo effects. (A nocebo effect is when a harmless treatment causes side-effects or worsening of symptoms because the person believes they may occur or expects them to occur.)

Knowing who received what also affects the therapists, who may be motivated to get more out of the therapy session if their patient got the “real deal”. And this problem is impossible to control for in so-called randomised controlled trials – still the gold standard in evaluating the effectiveness of drugs and treatments.

Also, non-clinical research on psychedelics faces problems. You may recall the graphic of a brain on psilocybin compared to one on a placebo (see below). Psilocybin increases the connections between different brain areas, which is represented in a colourful array of connecting lines.

This has become known as the “entropic brain hypothesis”. Psychedelics make your brain more flexible such that it returns to a child-like state of openness, novelty and surprise. This mechanism in turn has been hypothesised to underlie psychedelic therapy’s efficacy: by “liberating your brain” psychedelics can change entrenched and maladaptive patterns and behaviour. However, it turns out the picture is much more complicated than that.

Psychedelics constrict the blood vessels in your body and brain and this causes problems in the measurement of brain signals with MRI machines.

The graphic of the entropic brain may simply reflect the fact that the blood flow in the brain is dramatically altered under psilocybin. Also, it is far from clear what entropy exactly means – let alone how it can be measured in the brain.

A recent psilocybin study, which is yet to be peer-reviewed, found that only four out of 12 entropy measures could be replicated, casting further doubt on how applicable this mechanism of action is.

Although the story about psychedelics freeing your mind is compelling, it does not yet square well with the available empirical evidence.

These are just two examples that illustrate why it is important to be really cautious when you evaluate empirical studies in psychedelic science. Don’t trust findings at face value, but ask yourself the question: is the story too good or too simple to be true?

Personally, I have developed a healthy dose of scepticism when it comes to psychedelic science. I am still intrigued by psychedelics’ potential. They offer great tools for studying changes in consciousness. However, it is too early to conclude anything definite about their working mechanisms or their therapeutic potential. For this, we need more research. And I’m excited to contribute to that endeavour.

Michiel van Elk, Associate Professor, Cognitive Psychology, Leiden University

This article is republished from The Conversation under a Creative Commons license.

Read the original article.

Categories : General Interest HospitalsTags :

South Africa’s Traditional Medicines Should be Used in Modern Health Care

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Both the Khoi and the San believed in a mythical animal, resembling a cow, whose horns were thought to have medicinal attributes. This centuries-old medicine horn contained herbal remedies used by the Khoi-san. Credit: Rodger Smith

By Zelna Booth

Traditional medicines are part of the cultural heritage of many Africans. About 80% of the African continent’s population use these medicines for healthcare.

Other reasons include affordability, accessibility, patient dissatisfaction with conventional medicine, and the common misconception that “natural” is “safe”.

The growing recognition of traditional medicine resulted in the first World Health Organization global summit on the topic, in August 2023, with the theme “Health and Wellbeing for All”.

Traditional medicines are widely used in South Africa, with up to 60% of South Africans estimated to be reliant on traditional medicine as a primary source of healthcare.

Conventional South African healthcare facilities struggle to cope with extremely high patient numbers. The failure to meet the basic standards of healthcare, with increasing morbidity and mortality rates, poses a threat to the South African economy.

In my opinion, as a qualified pharmacist and academic with a research focus on traditional medicinal plant use in South Africa, integrating traditional medicine practices into modern healthcare systems can harness centuries of indigenous knowledge, increasing treatment options and provide better healthcare.

Recognition of traditional medicine as an alternative or joint source of healthcare to that of standard, conventional medicine has proven challenging. This is due to the absence of scientific research establishing and documenting the safety and effectiveness of traditional medicines, along with the lack of regulatory controls.

What are traditional medicines?

Traditional medicine encompasses a number of healthcare practices aimed at either preventing or treating acute or chronic complaints through the application of indigenous knowledge, beliefs and approaches. It incorporates the use of plant, animal and mineral-based products. Plant-derived products form the majority of treatment regimens.

Traditional medicine practices also have a place in ritualistic activities and communicating with ancestors.

South Africa is rich in indigenous medicinal fauna and flora, with about 2000 species of plants traded for medicinal purposes. In South Africa the provinces of KwaZulu-Natal, Gauteng, Eastern Cape, Mpumalanga and Limpopo are trading “hotspots”. The harvested plants are most often sold at traditional medicine muthi markets.

Uses of medicinal plants

Medicinal plants most popularly traded in South Africa include buchu, bitter aloe, African wormwood, honeybush, devil’s claw, hoodia, African potato, fever tea, African geranium, African ginger, cancer bush, pepperbark tree, milk bush and the very commonly consumed South African beverage, rooibos tea.

The most commonly traded medicinal plants in South Africa are listed below along with their traditional uses:

Buchu – Urinary tract infections; skin infections; sexually transmitted infections; fever; respiratory tract infections; high blood pressure; gastrointestinal complaints.

Bitter aloe – Skin infections; skin inflammation; minor burns.

African wormwood – Respiratory tract infections; diabetes, urinary tract disorders.

Honeybush – Cough; gastrointestinal issues; menopausal symptoms.

Devil’s claw – Inflammation; arthritis; pain.

Hoodia – Appetite suppressant.

African potato – Arthritis; diabetes; urinary tract disorders; tuberculosis; prostate disorders.

Fever tea – Respiratory tract infections; fever; headaches.

African geranium – Respiratory tract infections.

African ginger – Respiratory tract infections; asthma.

Cancer bush – Respiratory tract infections; menstrual pain.

Pepperbark tree – Respiratory tract infections; sexually transmitted infections.

Milk bush – Pain; ulcers; skin conditions.

Rooibos – Inflammation; high cholesterol; high blood pressure.

There are many ways in which traditional medicine may be used. It can be a drop in the eye or the ear, a poultice applied to the skin, a boiled preparation for inhalation or a tea brewed for oral administration.

Roots, bulbs and bark are used most often, and leaves less frequently. Roots are available throughout the year. There’s also a belief that the roots have the strongest concentration of “medicine”. Harvesting of the roots, however, poses concerns about the conservation of these medicinal plants. The South African government, with the draft policy on African traditional medicine Notice 906 of 2008 outlines considerations aimed at ensuring the conservation of these plants through counteracting unsustainable harvesting practises.

Obstacles to traditional medicine use

The limited research investigating interactions posed should a patient be making use of both traditional and conventional medicine is a concern.

During the COVID-19 pandemic, many patients used traditional remedies for the prevention of infection or treatment.

Understanding which traditional medicines are being used and how, their therapeutic effects in the human body, and how they interact with conventional medicines, would help determine safety of their combined use.

Certain combinations may have advantageous interactions, increasing the efficacy or potency of the medicines and allowing for reduced dosages, thereby reducing potential toxicity. These combinations could assist in the development of new pharmaceutical formulations.

Sharing information

The WHO in its Traditional Medicine Strategy for 2014-2023 report emphasised the need for using traditional medicine to achieve increased healthcare.

Key role players from both systems of healthcare need to be able to share information freely.

The need for policy development is key. Both conventional and traditional medicine practitioners would need to be aware of and engage with patients on all the medicines they are taking.

Understanding the whole patient

Patients often seek treatment from both conventional and traditional sources, which can lead to side effects or duplication in medications.

A comprehensive understanding of a patient’s health profile makes care easier.

This could also prevent treatment failures, promote patient safety, prevent adverse interactions and minimise risks.

A harmonious healthcare landscape would combine the strengths of both systems to provide better healthcare for all.

Zelna Booth, Pharmacist and Academic Lecturer (Pharmacy Practice Division, Department of Pharmacy and Pharmacology, University of the Witwatersrand), University of the Witwatersrand

This article is republished from The Conversation under a Creative Commons license.

Source: The Conversation