Canadian scientists recently reported that mice with a specific genetic variation – in the Parkinson’s-associated LRRK2 gene – differ in how they are able to deal with bacterial and viral infections.
Curiously, mice with the Parkinson’s-associated LRRK2 mutation could handle a bacterial infection better than normal mice, while mice with no LRRK2 protein struggled against the infection. And the researchers found that this effect was most prominent in female mice in particular.
And curiously, when the mice are infected with a dangerous virus, female mice with the Parkinson’s-associated LRRK2 mutation fared worse than their male counterparts.
In today’s post, we will discuss what LRRK2 is, review the new research, and explore what the sex difference could mean in terms of Parkinson’s.
Autumn colours. Source: Visitsunlimited
I am a big fan of Autumn.
The colours and the crisp/bracing air. I love the long, slow afternoon strolls and anticipation of the festive season to come.
But most of all I love the license to eat all the good wintery food. After a summer of salads and light food, there is nothing better that entering a warm cottage or pub, and smelling the hearty food (my wife if French – we navigate based on the quality of eateries).
Autumn bliss. Source: Askdrake
But there is a down side to autumn: The start of the flu season.
Luckily, our immune systems are pretty robust – doing battle on a moment-to-moment basis with all manner of pathogenic agents.
Recently, some Canadian scientists discovered something interesing about the immune system and it relates to Parkinson’s.
What did they find?
In addition to looking at current Parkinson’s disease research on this website, I like to look at where technological advances are taking us with regards to future therapies.
In July of this year, I wrote about a new class of engineered viruses that could potentially allow us to treat conditions like Parkinson’s disease using a non-invasive, gene therapy approach (Click here to read that post). At the time I considered this technology way off at some point in the distant future. Blue sky research. “Let’s wait and see” – sort of thing.
So imagine my surprise when an Italian research group last weekend published a new research report in which they used this futurist technology to correct a mouse model of Parkinson’s disease. Suddenly the distant future is feeling not so ‘distant’.
In today’s post we will review and discuss the results, and look at what happens next.
Technological progress – looking inside the brain. Source: Digitial Trends
I have said several times in the past that the pace of Parkinson’s disease research at the moment is overwhelming.
So much is happening so quickly that it is quite simply difficult to keep up. Not just here on the blog, but also with regards to the ever increasing number of research articles in the “need to read” pile on my desk. It’s mad. It’s crazy. Just as I manage to digest something new from one area of research, two or three other publications pop up in different areas.
But it is the shear speed with which things are moving now in the field of Parkinson’s research that is really mind boggling!
Take for example the case of Squalamine.
In February of this year, researchers published an article outlining how a drug derived from the spiny dogfish could completely suppress the toxic effect of the Parkinson’s associated protein Alpha Synuclein (Click here to read that post).
The humble dogfish. Source: Discovery
And then in May (JUST 3 MONTHS LATER!!!), a biotech company called Enterin Inc. announced that they had just enrolled their first patient in the RASMET study: a Phase 1/2a randomised, controlled, multi-center clinical study evaluating a synthetic version of squalamine (called MSI-1436) in people with Parkinson’s disease. The study will enrol 50 patients over a 9-to-12-month period (Click here for the press release).
Wow! That is fast.
Yeah, I thought so too, but then this last weekend a group in Italy published new research that completely changed my ideas on the meaning of the word ‘fast’. Regular readers will recall that in July I discussed amazing new technology that may one day allow us to inject a virus into a person’s arm and then that virus will make it’s way up to the brain and only infect the cells that we want to have a treatment delivered to. This represents non-invasive (as no surgery is required), gene therapy (correcting a medical condition with the delivery of DNA rather than medication). This new study used the same virus we discussed in July.
In large datasets, strange anomalies can appear that may tell us something new about a condition, such as the curious association between melanoma and Parkinson’s disease.
These anomalies can also appear in small datasets, such as the idea that spring babies are more at risk of developing Parkinson’s disease. But the smaller dataset results may be a bit misleading.
In today’s post, we will look at what evidence there is supporting the idea that people born in the spring are more vulnerable to Parkinson’s disease.
Spring lambs. Source: Wenatcheemumblog
When is your birthday?
More specifically, which month were you born in? Please feel free to leave your answer in the comments section below this post.
Why do I ask?
In 1987, an interesting research report was published in a scientific research book:
Title: Season of birth in parkinsonism.
Authors: Miura, T., Shimura, M., and Kimura, T.
Book: Miura T. (ed) Seasonality of birth:Progress in biometeorology, 1987.p157-162. Hague, Netherlands.
In the report, the researchers outlined a study that they had conducted on the inhabitants of an asylum for the aged in Tokyo (Japan). They had found not only a very high rate of Parkinsonism (6.5% of the inhabitants), but also that the majority of those individuals affected by the Parkinsonism were born in the first half of the year (regardless of which year they were actually born).
Sounds crazy right? (excuse the pun)
And that was probably what everyone who read the report thought….
…except that one year later this independent group in the UK published a very similar result:
In today’s post we will review recent research regarding one particular family of bacteria, Helicobacter pylori, and what they might be doing in relations to Parkinson’s disease.
In his magnificent book, I contain multitudes, science writer/journalist Ed Yong writes that we – every single one of us – release approximately 37 million bacteria per hour. By talking, breathing, touching, or simply being present in the world, we are losing and also picking up the little passengers everywhere we go.
Reminds me of that Pascal Mercier book “Night Train to Lisbon” – We leave something of ourselves behind when we leave a place,… I’m not sure if this is what he was referring to though.
Yong also points out that: 80% of the bacteria on your right thumb are different to the bacteria on your left thumb.
It’s a fascinating book (and no, I am not receiving any royalties for saying that).
Microbes. Source: NYmag
We have discussed microbes several times on this blog, particularly in the context of the gut and its connection to Parkinson’s disease (Click here, here and here to read some of those posts). Today we are going to re-visit one particular type of microbe that we have also discussed in a previous post: Helicobacter pylori.
Helicobacter pylori. Source: Helico
Last week a new piece of Parkinson’s disease research has been widely discussed in the media.
It involves Hepatitis – the viral version of it at least.
In today’s post we will review the research and discuss what it may mean for Parkinson’s disease.
A lewy body (brown with a black arrow) inside a cell. Source: Cure Dementia
A definitive diagnosis of Parkinson’s disease can only be made at the postmortem stage with an examination of the brain. Until that moment, all cases of Parkinson’s disease are ‘suspected’.
Critical to that postmortem diagnosis is the presence of circular shaped, dense clusters of proteins, called Lewy bodies (see the image above for a good example).
What causes Lewy bodies? We don’t know, but many people have theories.
This is Friedrich Heinrich Lewy (1885-1950).
Friedrich Lewy. Source: Lewy Body Society
As you can probably guess, Friedrich was the first to discover the ‘Lewy body’. His finding came by examining the brains of 85 people who died with Parkinson’s disease between 1908 – 1923.
In 1931, Friedrich Lewy read a paper at the International Congress of Neurology in Bern. During that talk he noted the similarities between the circular inclusions (called ‘negri bodies’) in the brains of people who suffered from rabies and his own Lewy bodies (observed in Parkinson’s disease).
A Negri body in a cell affected by rabies (arrow). Source: Nethealthbook
Given the similarities, Lewy proposed a viral cause for Parkinson’s disease.
Now, the idea that Parkinson’s disease could have a viral component has existed for a long time – even before Lewy made his conclusion. As we have previous mentioned, theories of viral causes for Parkinson’s have been circulating ever since the 1918 flu pandemic (Click here to read our post on this topic).
An example of post-encephalitic Parkinsonism. Source: Baillement
About the same time as the influenza virus was causing havoc around the world, another condition began to appear called ‘encephalitis lethargica‘ (also known as post-encephalitic Parkinsonism). This disease left many of the victims in a statue-like condition, both motionless and speechless – similar to Parkinson’s disease. Initially, it was assumed that the influenza virus was the causal factor, but more recent research has left us not so sure anymore.
Since then there, however, has been additional bits of evidence suggesting a viral role in Parkinson’s disease. Such as this report:
Title: Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration.
Author: Jang H, Boltz D, Sturm-Ramirez K, Shepherd KR, Jiao Y, Webster R, Smeyne RJ.
Journal: Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):14063-8.
The researchers in this study found that when they injected the highly infectious H5N1 influenza virus into mice, the virus progressed from the periphery (outside the brain) into the brain itself, where it induced Parkinson’s disease-like symptoms. The virus also caused a significant increase in the accumulation of the Parkinson’s associated protein Alpha Synuclein. Importantly, they witnessed the loss of dopamine neurons in the midbrain of the mice 60 days after resolution of the infection – that cell loss resembling what is observed in the brains of people with Parkinson’s disease.
The Parkinson’s associated protein alpha synuclein has also recently demonstrated anti-viral properties:
Title: Alpha-Synuclein Expression Restricts RNA Viral Infections in the Brain.
Authors: Beatman EL, Massey A, Shives KD, Burrack KS, Chamanian M, Morrison TE, Beckham JD.
Journal: J Virol. 2015 Dec 30;90(6):2767-82. doi: 10.1128/JVI.02949-15.
PMID: 26719256 (This article is OPEN ACCESS if you would like to read it)
David Beckham (not the football player) and his research colleagues introduced West nile virus to brain cells grown in cell culture and they observed an increase in alpha synuclein production. They also found that the brains of people with West nile infections had increased levels of alpha synuclein.
The researchers then injected West Nile virus into both normal mice and genetically engineered mice (which produced no alpha synuclein) and they found that the genetically engineered mice which produced no alpha synuclein died quicker than the normal mice. They reported that there was an almost 10x increase in viral production in the genetically engineered mice. This suggested to them that alpha synuclein may be playing a role in protecting cells from viral infections.
Interesting, but what about this new data involving Hepatitis?
Yes, indeed. Let’s move on.
Wait a minute, what is Hepatitis exactly?
The name Hepatitis comes from the Greek: Hepat – liver; and itis – inflammation, burning sensation. Thus – as the label suggests – Hepatitis is inflammation of liver tissue.
Hepatitis and the liver. Source: HealthandLovepage
It can be caused by infectious agents (such as viruses, bacteria, and parasites), metabolic changes (induced by drugs and alcohol), or autoimmune/genetic causes (involving a genetic predisposition).
The most common cause of hepatitis is viral.
There are five main types of viral hepatitis (labelled A, B, C, D, and E). Hepatitis A and E are mainly spread by contaminated food and water. Both hepatitis B and hepatitis C are commonly spread through infected blood (though Hepatitis B is mainly sexually transmitted). Curiously, Hepatitis D can only infect people already infected with hepatitis B.
Hepatitis A, B, and D are preventable via the use of immunisation. A vaccine for hepatitis E has been developed and is licensed in China, but is not yet available elsewhere
Hepatitis C, however, is different.
There is currently no vaccine for it, mainly because the virus is highly variable between strains and the virus mutates very quickly, making an effective vaccine a difficult task. A number of vaccines under development (Click here for more on this).
What is known about Hepatitis C and the brain?
Quite a bit.
Similar to HIV (which we discussed in a previous post), the hepatitis C virus (HCV) enters the brain via infected blood-derived macrophage cells. In the brain, it is hosted by microglial cells, which results in altered functioning of those microglial cells. This causes problems for neuronal cells – including dopamine neurons. For example, people infected with HCV have reduced dopamine transmission, based on brain imaging studies (Click here and here for more on this result).
Have there been connections between hepatitis C virus and Parkinson’s disease before?
Title: Hepatitis C virus infection: a risk factor for Parkinson’s disease.
Authors: Wu WY, Kang KH, Chen SL, Chiu SY, Yen AM, Fann JC, Su CW, Liu HC, Lee CZ, Fu WM, Chen HH, Liou HH.
Journal: J Viral Hepat. 2015 Oct;22(10):784-91.
The researchers in this study used data collected from a community-based screening program in north Taiwan which involved 62,276 people. The World Health Organisation (WHO) estimates that the prevalence of hepatitis C viral infection worldwide is approximately 2.2–3%, representing 130–170 million people. Taiwan is a high risk area for hepatitis, with antibodies for hepatitis viruses in Taiwan present in 4.4% in the general population (Source).
The researchers found that the significant association between hepatitis C viral infections and Parkinson’s disease – that is to say, a previous infection of hepatitis C increased the risk of developing Parkinson’s disease (by 40%). The researchers then looked at what the hepatitis C and B viral infections do to dopamine neurons growing in cell culture. They found that hepatitis C virus induced 60% dopaminergic cell death, while hepatitis B had no effect.
This study was followed up a few months later, by a second study suggesting an association between Hepatitis C virus and Parkinson’s disease:
Title: Hepatitis C virus infection as a risk factor for Parkinson disease: A nationwide cohort study.
Authors: Tsai HH, Liou HH, Muo CH, Lee CZ, Yen RF, Kao CH.
Journal: Neurology. 2016 Mar 1;86(9):840-6.
The researchers in this study wanted to investigate whether hepatitis C could be a risk factor for Parkinson’s disease. They did this by analyzing data from 2000-2010 drawn again from the Taiwan National Health Insurance Research Database.
The database included 49,967 people with either hepatitis B, hepatitis C or both, in addition to 199,868 people without hepatitis. During the 12 year period, 270 participants who had a history of hepatitis developed Parkinson’s disease (120 still had hepatitis C). This compared with 1,060 participants who were free of hepatitis, but went on to develop Parkinson’s disease.
When the researchers controlled for potentially confounding factors (such as age, sex, etc), the researchers found participants with hepatitis C had a 30% greater risk of developing Parkinson’s disease than the controls.
So if this has been demonstrated, why is this new study last week so important?
The answer is very simple: This study is not based on statistics from Taiwan – this new study has found the same result from a new population.
Title: Viral hepatitis and Parkinson disease: A national record-linkage study.
Authors: Pakpoor J, Noyce A, Goldacre R, Selkihova M, Mullin S, Schrag A, Lees A, Goldacre M.
Journal: Neurology. 2017 Mar 29. [Epub ahead of print]
These researchers used the English National Hospital Episode Statistics database and linked it to mortality data collected from 1999 till 2011. They too have found a strong association between hepatitis C and Parkinson’s disease (standardized rate ratio 1.51, 95% CI 1.18–1.9).
Curiously (and different from the previous studies), the researchers in this study also found a strong association for hepatitis B and Parkinson’s disease (standardized rate ratio 1.76, 95% CI 1.28–2.37). And these associations appear to be specific to Hepatitis B and C, as the investigators did not find any association between autoimmune hepatitis, chronic hepatitis, or HIV.
One important caveat with this new study, however, is that the authors could not
control for lifestyle factors (such as smoking or alcohol consumption). In addition, their system of linking medical records may underestimate the numbers of patients with
Parkinson’s disease as it would not take into account people with Parkinson’s disease who do not seek medical advice or those who are misdiagnosed (given a wrong diagnosis – it does happen!).
Regardless of these cautionary notes, the results still add to the accumulating evidence of an association between the virus that causes Hepatitis and the neurodegenerative condition of Parkinson’s disease.
But what about those people with Parkinson’s disease who have never had Hepatitis?
Yeah, this is a good question.
But there is a rather uncomfortable answer to it.
Here’s the rub: “Approximately 70%–80% of people with acute Hepatitis C do not have any symptoms” (Source: Centre for Disease Control). That is to say, the majority of people infected with the Hepatitis C virus will not be aware that they are infected. Some of those people who are infected may think that they have a case of the flu (HCV symptoms include fever, fatigue, loss of appetite,…), while others will simply not display any symptoms at all.
So many people with Parkinson’s disease may have had HCV, but never been aware of it.
And this is the really difficult part of researching the causal elements of Parkinson’s disease.
The responsible agent may actually leave little or no sign that they were ever present. For a long time, people have suggested that Parkinson’s disease is caused by a thief in the night – some agent that comes in, causes a problem and disappears without detection.
Perhaps Hepatitis is that thief.
But hang on a second, 60–70% of HCV infected people will go on to develop chronic liver disease (Source). Do people with Parkinson’s disease have liver issue?
Umm, well actually, in some cases: yes.
There have been studies of liver function in Parkinson’s disease where abnormalities have been found (Click here for more on this). And dopamine cell dysfunction has been seen in people with cirrhosis issues (Click here for more on this). In fact, the prevalence of Parkinsonism in people with cirrhosis has been estimated to be as high as 20% (and Click here for more on that).
So what are we saying? Hepatitis causes Parkinson’s disease???
No, we are not saying that.
Proving causality is the hardest task in science.
In addition, there have been a few studies in the past that have looked at viral infections as the cause of Parkinson’s disease that found strong associations with other viruses. For example this study:
Title: Infections as a risk factor for Parkinson’s disease: a case-control study.
Authors: Vlajinac H, Dzoljic E, Maksimovic J, Marinkovic J, Sipetic S, Kostic V.
Journal: Int J Neurosci. 2013 May;123(5):329-32.
In this study, the researchers found that Parkinson’s Disease was also significantly associated to mumps, scarlet fever, influenza, and whooping cough as well as herpes simplex 1 infections. They found no association between Parkinson’s disease and Tuberculosis, measles or chickenpox though.
This result raises the tantalizing possibility that other viruses may also be involved with the onset of Parkinson’s disease (it should be added though that this study was based on only 110 people with Parkinson’s (compared with 220 controls) in one particular geographical location (Belgrade, Serbia)).
So different viruses may cause Parkinson’s disease?
We are not saying that either, but we would like to see more research on this topic.
And the situation may actually be more complicated than we think.
Recently, it has been reported that previous infection with flaviviruses (such as dengue) actually enhances the effect of Zika virus infect (Click here to read more on this). That is to say, a prior infection by one particular virus may exacerbate the infection of another virus. It could be that a previous infection by one virus increases that chance that a later infection by another virus – a particular combination of viral infections – may result in Parkinsonian symptoms (we are simply speculating here).
Add to this complicated situation, the sheer number of unknown viruses. It is estimated that there are a minimum of 320,000 mammalian viruses still awaiting discovery (Click here for the source of this statistic), thus it is possible that additional unknown viruses may be involved with disease initiation for conditions like Parkinson’s disease.
A gang of unknown thieves in the night perhaps?
So what does it all mean?
Summing up: last week a new study was published that supported previous results that Hepatitis C viral infections could increase the risk of developing Parkinson’s disease. The results are important because they replicate previous findings from a different population of people.
The findings do not immediately mean that people with Hepatitis C are going to develop Parkinson’s disease, but it does suggest that they may be more vulnerable. The findings also suggest that more research is needed on the role of viral/infectious agents in the development of Parkinson’s disease.
We would certainly like to see more research in this area.
The banner for today’s post was sourced from Youtube
I was recently made aware of an interesting fact:
Approximately 5% of people with Human immunodeficiency virus (HIV) infections develop Parkinson’s disease-like features.
Why is this?
In today’s post we will try to understand what is going on, and what it may mean for Parkinson’s disease.
HIV (in green) budding (being released) from a blood cell (lymphocyte). Source: Wikipedia
Ok, let’s start at the beginning:
What is HIV?
Human immunodeficiency virus (or HIV) – as the name suggests – is the virus.
It causes the infection which gives rise to Acquired Immune Deficiency Syndrome (or AIDS). AIDS is a progressive failure of the immune system – the body loses its ability to fight infections. Without treatment, average survival period after infection with HIV is between 9 – 12 years.
HIV can be spread by the transfer of bodily fluids, such as blood and semen. The World Health Organisation (WHO) has estimated that approximately 36.9 million people worldwide were living with HIV/AIDS at the end of 2014 (that is equivalent to the entire population of Canada!).
The structure of the HIV virus. Source: Wikipedia
Does HIV affect the brain?
At postmortem examinations, less than 10% of the brains from HIV infected individuals are histologically normal (Source).
HIV is a member of the lentivirus family of viruses, which readily infect immune cells (such as blood cells). HIV can also infect other types of cells though, including those in the brain. HIV will usually enter the central nervous system within the first month following infection. It enters the brain via infected blood cells which come into contact with brain ‘immune system/helper’ cells such as microglia and macrophages at the blood-brain-barrier.
How HIV enters the brain. Source: Disease Models and Mechanisms
HIV can also infect astrocytes (albeit at a lower frequency than microglia and macrophages), by direct cell-cell contact with infected T cells (blood cells) at the blood-brain-barrier (No. 1 in the image above). After infecting astrocytes, there is dysfunction in the astrocyte and it will no longer be so supportive to the local neurons (No. 2 in the image above). Once inside the brain, HIV-infected macrophages will allow for infection of other macrophages and microglia (No. 3 in the image above), and all together these HIV-infected astrocytes and microglia will cause damage to neurons by releasing viral proteins (two in particular, called Tat and gp120) and additional nasty chemicals which are bad for the neurons (No. 4 in the image above). Finally, as the disease progresses, the protective layer of the blood-brain-barrier becomes compromised and HIV-infected T cells eventually enter the brain and they cause damage to neurons by releasing pro-inflammatory chemicals (making the environment harsh for neurons).
There is remarkably little evidence of HIV actually infecting neurons (Click here for a review on this), so any cell loss in the brain that is associated with HIV does not result from neurons themselves being infected. This may be due to the fact that neurons do not have the HIV receptors (such as CD4) on their cell membrane. Similarly, oligodendrocytes (a supporting cell) does not appear to be easily infected by HIV. The bulk of the infected cells in the brain appear to be of the microglial, macrophage and astrocytes. And without these supporting cells doing their jobs in a normal fashion, it is easy to see how neurons can start dying off.
The severity, characteristics and distribution of HIV-induced injury in the brain varies greatly between affected individuals. It is most likely associated with the viral load (or the number of viral particles) in the brain, which can vary from a few thousand to more than a million copies per mL.
Do HIV-infected people show any signs of the virus entering the brain?
For the majority of people infected with HIV, this entry of the virus into the nervous system is neurologically asymptomatic (meaning they will not notice it), except for the occasional mild headache (for more on this read this review). As a result of the HIV virus entering the brain, however, many infected individuals will suffer from a specific set of neurological disorders, collectively called the AIDS dementia complex (ADC) (also known as HIV-associated cognitive/motor complex, or simply HIV dementia).
So how does HIV infection result in Parkinson’s disease-like features?
As we have suggested in the introduction to this post, on rare occasions (approximately 5% of cases), HIV-infected patients may present an illness virtually identical to Parkinson’s disease. More commonly, people with HIV will exhibit an increased sensitivity to dopamine receptor-blocking agents, such as drugs with a low potential for inducing Parkinsonism, (for example prochlorperazine and metoclopropamide).
The exact mechanism by which HIV infection results in Parkinson’s disease-like features is the subject of debate, but what is clear is that the basal ganglia (a structure involved in Parkinson’s disease) faces the brunt of the HIV infection in the brain. HIV-infected microglia and macrophage are most prominent in the basal ganglia when compared to other brain regions (Click here and here for more on this), and the basal ganglia is where the chemical dopamine from the midbrain is being released.
In addition, there are other changes in the brains of HIV infected people which may aid in the appearance of Parkinsonian features:
Title: Increased frequency of alpha-synuclein in the substantia nigra in human immunodeficiency virusinfection.
Authors: Khanlou N, Moore DJ, Chana G, Cherner M, Lazzaretto D, Dawes S, Grant I, Masliah E, Everall IP; HNRC Group.
Journal: J Neurovirol. 2009 Apr;15(2):131-8.
PMID: 19115126 (This article is OPEN ACCESS if you would like to read it)
The researchers in this study used staining techniques to look at the amount of alpha synuclein – the Parkinson’s associated protein – in slices of brain tissue taken from postmortem autopsies of 73 HIV+ individuals aged between 50 and 76 years of age.
The presence of alpha synuclein in the substantia nigra (an area of the brain affected by Parkinson’s disease) was a lot higher in the HIV+ brains when compared with healthy control samples (16% of the HIV+ brains had high levels of alpha synclein vs 0% for the healthy brains).
Interestingly, nearly all of the brains analysed (35 out of 36 HIV+ brains) had high levels of the Alzheimer’s disease associated protein, beta amyloid (which again raises the question of whether beta amyloid could be playing a defensive role in infections – see our previous post on this). Also interesting, was that there was no correlation between these proteins being present and the age of the person at death – that is to say, older brains did not have more of these proteins when compared with younger brains.
There are also additional ways in which HIV could be causing Parkinson’s-like features, such as:
- HIV has been shown to affect the protein levels of Parkinson’s disease associated proteins, such as DJ1 and Lrrk2 (Click here and here to read more on this).
- HIV can, in some cases, increase the level of Dopamine transporter, which would reduce the levels of free floating dopamine in the brain (Click here to read more about this).
How is HIV treated?
Treating HIV. Source: NPR
There is currently no cure for HIV infection.
There are, however, treatments which help to slow the virus down. These are called Anti-retroviral drugs (HIV is a retrovirus). There are different kinds of anti-retroviral drugs, which act at different stages of the HIV life cycle. Combinations of several anti-retroviral drugs (generally three or four) is known as ‘Highly Active Anti-Retroviral Therapy'(or HAART).
Mechanism by which four classes of anti-retroviral drugs work against HIV. Source: Wikipedia
As the schematic image above highlights, there are many ways to slow down the HIV virus. For example, you can prevent it from attaching to a cell and fusing with the cell membrane (fusion inhibitors). By treating HIV infected people with multiple medications attacking different parts of the HIV life cycle, the virus has been slowed down.
Does HAART treatments for HIV help with these Parkinson’s-like features?
In some cases, the answer appears to be yes.
There are numerous case studies in the literature which demonstrate the alleviation of HIV-associated Parkinsonian symptoms with HAART, such as this report:
Title: Parkinsonism as the presenting manifestation of HIV infection: improvement on HAART.
Authors: Hersh BP, Rajendran PR, Battinelli D.
Journal: Neurology. 2001 Jan 23;56(2):278-9.
In this study the researchers described the case of a 37 year old man who developed Parkinson’s like features in the setting of an HIV infection, which were resolved after 1 year of HAART.
Over a period of 4 months, the man developed co-ordination issue, clumsiness and an irregular tremor in his right hand (there was, however, no resting tremor). He noted a generalised slowness and exhibited a tendency towards decreased right arm swinging. He also developed dystonia in the right hand/arm. Following L-dopa treatment (25/100; one tablet 3x per day) there was improvement in balance & co-ordination, speech, facial expression, and the tremor (L-dopa does appear to improve most cases of HIV-associated Parkinson’s-like features).
Six months after first displaying these Parkinsonian features (and two month after initiating L-dopa treatment), the subject was placed on HAART treatment. Four months later, he discontinued L-dopa treatment and 12 months after starting the HAART regime his Parkinsonian features were largely resolved.
What does this mean for Parkinson’s disease?
This post was written for the research community rather than people with Parkinson’s disease. I thought the fact that some people with HIV can start to have Parkinson’s like features was an interesting curiosity and wanted to share/spread the information.
Having said that, this post raises some really interesting questions, such as if a virus like HIV can have this effect on the brain, could other viruses be having similar effects? Could some cases of Parkinson’s disease simply be the result of a viral infection? Either multiple hits from a particular virus or different viruses each taking a varying toll over the course of a life time.
This idea would explain many of the curious features of Parkinson’s disease, such as:
- the asymmetry of the symptoms (people with Parkinson’s usually have the disease starting on one side of the body.
- the fact that some cells in the brain are more vulnerable to the disease than others (perhaps they are more receptive to a particular virus).
- the protein clusterings in the cells (Lewy bodies may be defensive efforts against viral infections).
As we have previous mentioned, theories of viral causes for Parkinson’s have been circulating ever since the 1918 flu pandemic (Click here to read our previous post on this topic). About the same time as the influenza virus was causing havoc around the world, another condition began to appear called ‘encephalitis lethargica‘. This disease left many of the victims in a statue-like condition, both motionless and speechless – similar to Parkinson’s disease. Initially, it was assumed that the influenza virus was the causal factor, but more recent research has left us not so sure anymore.
The point is, however, perhaps it is time for us to re-examine the possibility of a viral agent being involved in the development of Parkinson’s disease.
There is new technology that allows us to determine the viral history of each individual from a simple blood test (Click here for more on this), so it would be interesting to compare blood samples from people with Parkinson’s disease with healthy controls to determine any differences.
In addition to the overall question of a viral role in Parkinson’s disease, there also remains the question of why only a small fraction of people with HIV are affected by Parkinsonisms. It could be interesting to genetically screen those people with HIV that exhibit Parkinsonisms and compare them with people with HIV that do not. Do those affected individuals have recognised Parkinson’s related genetic mutations? Or do they have novel genetic variations that could tell us more about Parkinson’s disease?
Food for thought. Would be happy to hear others thoughts.
The banner for today’s post was sourced from AidsServices