Tagged: Insulin

Self monitoring: there’s something in your eye

Self tracking/monitoring has become a popular habit for the general population with the introduction of products like Fitbit and Apple watch.

It is particularly useful for groups like the Parkinson’s community though, who are tired of having just one hour per year of assessments with their neurologist.

In today’s post, we will look at some new tracking/monitoring technologies that are being developed that could have important implications for not only how we assess Parkinson’s disease, but also for how we treat it.



Homo deus. Source: RealClearLife

I have recently finished reading ‘Homo Deus‘ by Yuval Noah Harari – the excellent follow-up to his previous book ‘Sapiens‘ (which is an absolute MUST READ!). The more recent book provides an utterly fascinating explanation of how we have come to be where we will be in the future (if that makes any sense).

In the final few chapters, Harari discusses many of the technologies that are currently under development which will change the world we live in (with a lot of interesting and cautionary sections on artificial intelligence – the machines that will know vastly more about us than we know about ourselves).

Of particular interest in this part of the book was a section on the Google-Novartis smart lens.

What is the Google-Novartis smart lens?

In 2014, a company called Alcon, which is a wholly owned subsidiary of Novartis formed a collaboration with the Google offshoot Verily Life Sciences that would focus on developing smart lens.

The initial project is rather ambitious: develop and take to the clinic a glucose-sensing contact lens for people with diabetes. The idea has been particularly championed by Google founder Sergey Brin (a prominent figure within the Parkinson’s community with his significant contributions to Parkinson’s research each year).

People with diabetes have to keep pricking their finger over the course of a day in order to check the levels of insulin in their blood. A less laborious approach would be welcomed by the diabetic world (an estimated 415 million people living with diabetes in the world).

This is what the lens may eventually look like:

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DPP-4: Not a Star Wars character

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Dipeptidyl peptidase-4 (or DPP-4) is an enzyme that breaks down the protein (GLP-1) that stimulates insulin release in your body. 

Inhibitors of DPP-4 are used in the treatment of Type 2 diabetes, because they help increase insulin levels in the body.

Recently some Swedish researchers noticed something curious about DPP-4 inhibitors: They appear to reduce the risk of developing Parkinson’s disease.

In today’s post, we will review what DPP-4 inhibitors do and look at how this could be reducing the risk of Parkinson’s disease.


januvia

Sitagliptin. Source: Diabetesmedicine

Last year an interesting research report about a class of medications that could possibly reduce the risk of developing Parkinson’s disease was published in the journal Movement disorders:

SWeds

Title: Reduced incidence of Parkinson’s disease after dipeptidyl peptidase-4 inhibitors-A nationwide case-control study.
Authors: Svenningsson P, Wirdefeldt K, Yin L, Fang F, Markaki I, Efendic S, Ludvigsson JF.
Journal: Movement Disorders 2016 Jul 19.
PMID: 27431803

In this study, the investigators used the Swedish Patient Register, to find the medical records of 980 people who were diagnosed with Parkinson’s disease but also had type 2 diabetes. Importantly, all of the subjects had been treated with Type 2 diabetes medication for at least 6 months prior to the date of Parkinson’s being diagnosed.

For comparative sake, they selected 5 controls (non-Parkinsonian) with Type 2 diabetes (n = 4,900) for each of their Parkinsonian+diabetes subjects. They next looked at whether GLP-1R agonists (such as Exenatide), Dipeptidyl peptidase-4 (or DPP-4) inhibitors, or any other oral Type 2 diabetic medication can influence the incidence of Parkinson’s disease.

Now, if all things are considered equal, then when looking at each diabetes medication there should be 1 person in the Parkinson’s disease + Type 2 diabetes for every 5 people in the Type 2 diabetes control group taking each medication right? That is because there are almost 1000 people in the first group and 5000 in the second group.

But this is not what the researchers found.

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Exenatide: One step closer to joblessness!

bydureon

The title of today’s post is written in jest – my job as a researcher scientist is to find a cure for Parkinson’s disease…which will ultimately make my job redundant! But all joking aside, today was a REALLY good day for the Parkinson’s community.

Last night (3rd August) at 23:30, a research report outlining the results of the Exenatide Phase II clinical trial for Parkinson’s disease was published on the Lancet website.

And the results of the study are good:while the motor symptoms of Parkinson’s disease subject taking the placebo drug proceeded to get worse over the study, the Exenatide treated individuals did not.

The study represents an important step forward for Parkinson’s disease research. In today’s post we will discuss what Exenatide is, what the results of the trial actually say, and where things go from here.


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Last night, the results of the Phase II clinical trial of Exenatide in Parkinson’s disease were published on the Lancet website. In the study, 62 people with Parkinson’s disease (average time since diagnosis was approximately 6 years) were randomly assigned to one of two groups, Exenatide or placebo (32 and 30 people, respectively). The participants were given their treatment once per week for 48 weeks (in addition to their usual medication) and then followed for another 12-weeks without Exenatide (or placebo) in what is called a ‘washout period’. Neither the participants nor the researchers knew who was receiving which treatment.

At the trial was completed (60 weeks post baseline), the off-medication motor scores (as measured by MDS-UPDRS) had improved by 1·0 points in the Exenatide group and worsened by 2·1 points in the placebo group, providing a statistically significant result (p=0·0318). As you can see in the graph below, placebo group increased their UPDRS motor score over time (indicating a worsening of motor symptoms), while Exenatide group (the blue bar) demonstrated improvements (or a lowering of motor score).

graph

Reduction in motor scores in Exenatide group. Source: Lancet

This is a tremendous result for Prof Thomas Foltynie and his team at University College London Institute of Neurology, and for the Michael J Fox Foundation for Parkinson’s Research who funded the trial. Not only do the results lay down the foundations for a novel range of future treatments for Parkinson’s disease, but they also validate the repurposing of clinically available drug for this condition.

In this post we will review what we know thus far. And to do that, let’s start at the very beginning with the obvious question:

So what is Exenatide?

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A drug from Kalamazoo

diabetes60systemreview-1024x683

Last week a research report was published in the prestigious journal Science Translational Medicine (that means that it’s potentially really important stuff). The study involved a new drug that is being clinically tested for diabetes.

In last week’s study, however, the new drug demonstrated very positive effects in Parkinson’s disease.

In today’s post we will review the new study and discuss what it means for Parkinson’s.


Diabetic patient doing glucose level blood test

Diabetic checking blood sugar levels. Source: Gigaom

FACT:  One in every 19 people on this planet have diabetes (Source: DiabetesUK).

It is expected to affect one person in every 10 by 2040.

Diabetes (or ‘Diabetes mellitus’) is basically a group of metabolic diseases that share a common feature: high blood sugar (glucose) levels for a prolonged period. There are three types of diabetes:

  • Type 1, which involves the pancreas being unable to generate enough insulin. This is usually an early onset condition (during childhood) and is controlled with daily injections of insulin.
  • Type 2, which begins with cells failing to respond to insulin. This is a late/adult onset version of diabetes that is caused by excess weight and lack of exercise.
  • Type 3, occurs during 2-10% of all pregnancies, and is transient except in 5-10% of cases.

In all three cases inulin plays an important role.

What is insulin?

Insulin is a chemical (actually a hormone) that our body makes, which allows us to use sugar (‘glucose’) from the food that you eat.

Glucose is a great source of energy. After eating food, our body releases insulin which then attaches to cells and signals to those cells to absorb the sugar from our bloodstream. Without insulin, our cells have a hard time absorbing glucose. Think of insulin as a “key” which unlocks cells to allow sugar to enter the cell.

What does diabetes have to do with Parkinson’s disease?

So here’s the thing: 10–30% of people with Parkinson’s disease are glucose intolerant (some figures suggest the percentage may be as high as 50%).

Why?

We do not know.

Obviously, however, this ratio is well in excess of the 6% prevalence rate in the general public (Source:DiabetesUK). We have discussed the curious relationship between diabetes and Parkinson’s disease in a previous post (click here to read it).

And the relationship between Parkinson’s disease and diabetes is not a one way street: A recent analysis of 7 large population studies found that people with diabetes are almost 40% more likely to develop Parkinson’s disease that non-diabetic people (Click here for more on this).

EDITORIAL NOTE HERE: We would like to point out that just because a person may have diabetes, it does not necessarily mean that they will go on to develop Parkinson’s disease. There is simply a raised risk of developing the latter condition. It is good to be aware of these things, but please do not panic.

We have no idea why there is an association between diabetes and Parkinson’s disease, but each month new pieces of research are published that support the connection between Parkinson’s and diabetes, and this all provides encouraging support for an ongoing clinical trial (which we will discuss below).

So what research has been done?

Well, just this year alone there have been some interesting studies reported. The first piece of research deals with a drug that is used for treating type-2 diabetes:

Metformin

Title: Metformin Prevents Nigrostriatal Dopamine Degeneration Independent of AMPK Activation in Dopamine Neurons.
Author: Bayliss JA, Lemus MB, Santos VV, Deo M, Davies JS, Kemp BE, Elsworth JD, Andrews ZB.
Journal: PLoS One. 2016 Jul 28;11(7):e0159381.
PMID: 27467571       (This article is OPEN ACCESS if you would like to read it)

Metformin (also known as Glucophage) has been one of the most frequently prescribed drugs for the treatment of type 2 diabetes since 1958 in the UK and 1995 in the USA. The mechanism by which Metformin works is not entirely clear, but it does appear to increase the body’s ability to recognise insulin.

Metformin treatment has previously been found to be neuroprotective. The researchers in this study wanted to determine if a protein called ‘AMPK’ was involved in that neuroprotective effect. They generated cells that do not contain AMPK and grew dopamine neurons – the brain cells badly affected by Parkinson’s disease.

In both cell cultures and in mice, the researchers found that Metformin was neuroprotective both in normal conditions and in the absence of AMPK. The study could not explain how the neuroprotective potential of Metformin was working, but it adds to the accumulating pile of evidence that some diabetes treatments may be having very positive effects in Parkinson’s disease.

A second piece of research from early this year goes even further:

SWeds

Title: Reduced incidence of Parkinson’s disease after dipeptidyl peptidase-4 inhibitors-A nationwide case-control study.
Authors: Svenningsson P, Wirdefeldt K, Yin L, Fang F, Markaki I, Efendic S, Ludvigsson JF.
Journal: Movement Disorders 2016 Jul 19.
PMID: 27431803

Using the Swedish Patient Register, the researchers of this study identified 980 people with Parkinson’s disease who were also diagnosed with type 2 diabetes between July 1, 2008, and December 31, 2010. For comparative sake, they selected 5 controls (non-Parkinsonian) with type 2 diabetes (n = 4,900) for each of their Parkinsonian+diabetic subjects. Their analysis found a significant decrease in the incidence of Parkinson’s disease among individuals with a history of DPP-4 inhibitor intake.

DPP-4 inhibitors work by blocking the action of DPP-4, which is an enzyme that destroys the hormone incretin. Incretin helps the body produce more insulin only when it is needed and reduce the amount of glucose being produced by the liver when it is not needed. By blocking DPP-4, we are increasing the production of insulin.

Authors concluded that ‘clinical trials with DPP-4 inhibitors may be worthwhile’ in people with Parkinson’s disease.

So what was published last week?

Metabolic Solutions Development is a Kalamazoo (Michigan)-based company that is developing a new drug (MSDC-0160) to treat type 2 diabetes. Last week, Prof Patrik Brundin and colleagues from the Van Andel Institute in Grand Rapids published a research report that suggested MSDC-0160 may have very beneficial effects in Parkinson’s disease:

brundin-title

Title: Mitochondrial pyruvate carrier regulates autophagy, inflammation, and neurodegeneration in experimental models of Parkinson’s disease.
Authors: Ghosh A, Tyson T, George S, Hildebrandt EN, Steiner JA, Madaj Z, Schulz E, Machiela E, McDonald WG, Escobar Galvis ML, Kordower JH, Van Raamsdonk JM, Colca JR, Brundin P.
Journal: Sci Transl Med. 2016 Dec 7;8(368):368ra174.
PMID: 27928028

The drug from Kalamazoo, MSDC-0160, functions by reducing the activity of a recently identified protein that carries pyruvate into mitochondria.

What does this mean?

Pyruvate is a very important molecule in our body. The body can make glucose from pyruvate through a process called gluconeogenesis, which simply means production of new glucose. Thus, pyruvate is essential in providing cells with fuel to create energy (for more on pyruvate, click here for a good review article).

Pyruvate is carried into the power house of the cell – the mitochondria – by a protein called mitochondrial pyruvate carrier (MPC). The drug from Kalamazoo, MSDC-0160, is a blocker of MOC. It reduces the activity of MPC.

MPC also has other functions. It is known to be a key controller of certain cellular processes that influences mammalian target of rapamycin (mTOR) activation. mTOR responds to signals to nutrients, growth factors, and cellular energy status and controls the cells response. For example, insulin can signal to mTOR the status of glucose levels in the body. mTOR also deals with infectious or cellular stress-causing agents, thus it could be involved in a cells response to conditions like Parkinson’s disease.

ncb2763-f11

Things that activate mTOR. Source: Selfhacked

Given the interaction with mTOR, the researchers in Michigan hypothesised that MSDC-0160 might reduce the neurodegeneration of dopaminergic neurons in animal models of Parkinson’s disease.

And this is exactly what they found.

The researchers reported that MSDC-0160 protected dopamine neurons in a mouse model of Parkinson’s disease. It also protected human midbrain dopamine neurons grown in cell culture when they were exposed to a toxic chemical. In addition, it demonstrated neuroprotective effects in a worm (called Caenorhabditis elegans) that produces a lot of the parkinson’s related protein alpha synuclein. MSDC-0160 even slowed the cell loss observed in a genetically engineered mouse that exhibits a slow loss of dopamine neurons. Basically, treatment with MSDC-0160 protected the cells from whatever the researcher threw at them.

How did it do this?

The researchers found that MSDC-0160 was reducing mTOR activity and also initiating a process called autophagy (which is the garbage disposal system of the cell). By kick starting the rubbish removal system, the cells were healthier. In addition, treatment with MSDC-0160 resulted in less inflammation – or activation of the immune system – in the brain.

Sounds very interesting. When do clinical trials start?

We’re not sure. They will most likely be in the planning stages though. If MSDC-0160 is approved for diabetes, it will be easier to have it approved for Parkinson’s disease as well.

Other diabetes drugs, however, are currently being tested in clinical trials for Parkinson’s disease. Of particular interest is Exenatide, which is just finishing a placebo-controlled, double blind phase 2 clinical trial. We are expecting the results for that trial early next year. Previous clinical studies suggested very positive results for Exenatide:

 

diabetes

Title: Exenatide and the treatment of patients with Parkinson’s disease.
Authors: Aviles-Olmos I, Dickson J, Kefalopoulou Z, Djamshidian A, Ell P, Soderlund T, Whitton P, Wyse R, Isaacs T, Lees A, Limousin P, Foltynie T.
Journal: J Clin Invest. 2013 Jun;123(6):2730-6.
PMID: 23728174     (This study is OPEN ACCESS if you would like to read it)

The researchers running this clinical study gave Exenatide to a group of 21 patients with moderate Parkinson’s disease and evaluated their progress over a 14 month period (comparing them to 24 control subjects with Parkinson’s disease). Exenatide was well tolerated by the participants, although there was some weight loss reported amongst many of the subjects (one subject could not complete the study due to weight loss). Importantly, Exenatide-treated patients demonstrated improvements in their clinician assessed PD ratings, while the control patients continued to decline. Interestingly, in a two year follow up study – which was conducted 12 months after the patients stopped receiving  Exenatide – the researchers found that patients previously exposed to Exenatide demonstrated a significant improvement (based on a blind assessment) in their motor features when compared to the control subjects involved in the study.

bydureon

Exenatide. Source: Diatribe

The results of that initial clinical study were intriguing and exciting, but it is important to remember that the study was open-label: the subjects knew that they were receiving the drug. This means that we can not discount the placebo effect causing some of the beneficial effects reported.

And Exenatide is not the only diabetes drug being tested

Pioglitazone is another licensed diabetes drug that is now being tested in Parkinson’s disease. It reduces insulin resistance by increasing the sensitivity of cells to insulin. Pioglitazone has been shown to offer protection in animal models of Parkinson’s disease (click here and here for more on this). And the drug is currently being tested in a clinical trial.

So what does it all mean?

People with diabetes appear to be more vulnerable than the general population to developing Parkinson’s disease, and many people with Parkinson’s disease have glucose processing issues. It would be very interesting to better understand the link between Parkinson’s disease and diabetes. Why is it that so many people with Parkinson’s disease are glucose intolerant? And why do so many people with diabetes go on to develop Parkinson’s? Answering either of these questions might provide further insight into how both conditions function. And given that drugs associated with one appear to help with the other only strengthens the curious association.

As mentioned above, 2017 will bring the results of Exenatide clinical trial, upon which a lot of hope is riding. If it provides positive benefits, then we will finally have a treatment that can slow the progression of the disease. In addition, we will be able to delve more deeply into how Exenatide is causing it’s effect. Positive outcomes for Exenatide will also open the flood gates for many of the other clinically approved diabetes medications which could be trialled on people with Parkinson’s disease.

So despite how you may be feeling about 2017 (based on the events of 2016), we here at the SoPD believe that there is a lot to look forward to in the new year.


The banner for today’s post was sourced from Diabetes60systems

Diabetes, Monster saliva, and Parkinson’s disease

 

If I were to tell you that there exists a miraculous elixir derived from the saliva of a monster and it may aid us in the treatment of Parkinson’s disease, would you think me mad?


 

In 1974, a small study was published in the Journal of Chronic Diseases that presented a rather startling set of results:

Lipman-title

In the study, Lipman and colleagues conducted some routine glucose tolerance tests on a group of 56 people with Parkinson’s Disease (7 additional subjects with Parkinson’s were excluded because they had been previously diagnosed with diabetes).

After being asked to fast overnight, the  subjects were then given 100g of glucose and blood samples were collected from them every hour for 3 hours. When the glucose levels in the blood were measured and compared with the results of 5 previous studies conducted on normal healthy adults of the same age (one of those studies involved 7000 participants), it was found that the people with Parkinson’s disease in the Lipman study had a much higher average level of glucose in their blood than all of the other 5 studies looking at healthy individuals.

Shockingly, almost half (46.4%) of the participants in the Lipman study actually fulfilled the criteria for a diagnosis of diabetes.

More recent survey data has revealed that diabetes is established in between 8–30% of people with Parkinson’s disease (click here for more on this) – obviously this is in excess of the approximately 6% prevalence rate in the general public (Source: DiabetesUK).

What is diabetes?

‘Diabetes mellitus’ is what we commonly refer to as diabetes. It is basically a group of metabolic diseases that share a common feature: high blood sugar (glucose) levels for a prolonged period.

Diabetic patient doing glucose level blood test

Diabetic patient doing glucose level blood test using ultra mini glucometer and small drop of blood from finger and test strips isolated on a white background. Device shows 115 mg/dL which is normal

Source: Gigaom

There are three types of diabetes:

  • Type 1, which involves the pancreas being unable to generate enough insulin. This is usually an early onset condition (during childhood) and is controlled with daily injections of insulin.
  • Type 2, which begins with cells failing to respond to insulin. This is a late/adult onset version of diabetes that is caused by excess weight and lack of exercise.
  • Type 3, occurs during 2-10% of all pregnancies, and is transient except in 5-10% of cases.

What is this stuff called insulin?

Insulin is a hormone – that our body makes – which allows us to use sugar (glucose) from the food that you eat. Glucose is a great source of energy. After eating, our body is releases insulin which then attaches to cells and signals to those cells to absorb the sugar from our bloodstream. Without insulin, our cells have a hard time absorbing glucose. Think of insulin as a “key” which unlocks cells to allow sugar to enter the cell.

Ok, so how is it all connected to Parkinson’s disease?

The short answer is ‘we currently don’t know’.

There have, however, been numerous studies now that suggest an association between diabetes and Parkinson’s disease. The first of these studies was:

Driver_title
Title: Prospective cohort study of type 2 diabetes and the risk of Parkinson’s disease.
Authors: Driver JA, Smith A, Buring JE, Gaziano JM, Kurth T, Logroscino G.
Journal: Diabetes Care. 2008 Oct;31(10):2003-5.
PMID: 18599528

In this study, 21,841 male doctors (participants in the Physicians’ Health Study) were followed over 23 years. The researchers found that people with diabetes had an increased risk of developing Parkinson’s disease risk. Interestingly they reported that the highest Parkinson’s disease risk was seen in individuals with short-duration, older-onset diabetes.

In another study:

Xu_title
Title: Diabetes and risk of Parkinson’s disease.
Authors: Xu Q, Park Y, Huang X, Hollenbeck A, Blair A, Schatzkin A, Chen H.
Journal: Diabetes Care. 2011 Apr;34(4):910-5. doi: 10.2337/dc10-1922. Epub 2011 Mar 4.
PMID: 21378214

This study came from another long term study, which was following 288,662 participants of the National Institutes of Health-AARP Diet and Health Study. The researchers found that the risk of Parkinson’s disease was approximately 40% higher among diabetic patients than among participants without diabetes. In this study, however, the analysis showed that the risk was largely limited to individuals who had diabetes for more than 10 years.

A third study:

Schernhammer_title

Title: Diabetes and the risk of developing Parkinson’s disease in Denmark.
Authors: Schernhammer E, Hansen J, Rugbjerg K, Wermuth L, Ritz B.
Title: Diabetes Care. 2011 May;34(5):1102-8.
PMID: 21411503

Using data from the nationwide Danish Hospital Register hospital records, the researchers found that having diabetes was associated with a 36% increased risk of developing Parkinson’s disease. Interestingly, they reported that the risk was stronger in women and patients with early-onset Parkinson’s disease (eg. diagnosed before the age of 60 years).


EDITORIAL NOTE HERE: It is important to understand that these studies do not suggest that having diabetes will naturally lead to Parkinson’s disease. They are simply pointing out that diabetics have an increased risk of developing the condition. We present this data here for informative purposes and to make people aware.

It is of interest to note that there is also an association between diabetes and Alzheimer’s disease (click here and here for more on this). Thus Parkinson’s disease is not the only neurodegenerative condition associated with diabetes. 


Is the association between Parkinson’s disease and diabetes genetic?

At present, the answer is no.

The connection between diabetes and Parkinson’s disease does not appear to be genetic, as genome wide sequencing studies have found no common mutations or associations between the two conditions (click here for more on this).

So what are we doing with this knowledge?

Dragons

This is the Gila monster (Source: Californiaherps).

Cute huh?

Named after the Gila River Basin of New Mexico and Arizona, where these lizards are found found, the saliva of the Gila monster was found to have some rather amazing properties with regards to the management of type 2 diabetes. This was due largely to a protein extracted from the saliva, called exendin-4. Scientists have made a synthetic version of exendin-4 which they have called Exenatide.

When tested in a three year clinical trial, Exenatide was found to return people with type 2 diabetes to healthy sustained glucose levels and progressive weight loss.

Exenatide is a glucagon-like peptide-1 (GLP-1) agonist. These types of drugs work by mimicking the functions of the natural hormones in your body that help to lower blood sugar levels after meals. They do this by aiding the release of insulin from the pancreas, blocking a hormone that causes the liver to release its stored sugar into the bloodstream, and slowing glucose absorption into the bloodstream.

Great, but what has this got to do with Parkinson’s disease?!?

Exenatide has also been found to have impressive results in both animal models of Parkinson’s disease and in an open-label clinical trial.

The first study to report a positive effect of Exenatide in a Parkinson’s disease model was:

Bertilsson-title

Title: Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of Parkinson’s disease.
Authors: Bertilsson G, Patrone C, Zachrisson O, Andersson A, Dannaeus K, Heidrich J, Kortesmaa J, Mercer A, Nielsen E, Rönnholm H, Wikström L.
Journal: J Neurosci Res. 2008 Feb 1;86(2):326-38.
PMID: 17803225

In this study, the scientists found that exendin-4 (aka Exenatide) improved both behavioural motor ability and protected dopamine neurons in a rodent model of Parkinson’s disease (and the drug was given 5 weeks after the animals developed the motor features). How these results were achieved – the biology behind the results – is unclear, but the effect was interesting enough to encourage other groups to also test Exenatide and they found similar results:

Harkavyi-title

Title: Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson’s disease.
Authors: Harkavyi A, Abuirmeileh A, Lever R, Kingsbury AE, Biggs CS, Whitton PS.
Journal: J Neuroinflammation. 2008 May 21;5:19. doi: 10.1186/1742-2094-5-19.
PMID: 18492290    (This study is OPEN ACCESS if you would like to read it)

The scientists in this study tested exendin-4 (aka Exenatide) on two different rodent models of Parkinson’s disease and they found similar results to the previous study. The drug was given 1 week after the animals developed the motor features, but still positive effects were observed.

These (and other) initial results led to the initiation of a clinical trial. Given that Exenatide is already approved for use with diabetes, testing the drug in Parkinson’s disease was a relatively straightforward process (funded by the Cure Parkinson’s Trust).

Olmos-title

Title: Exenatide and the treatment of patients with Parkinson’s disease.
Authors: Aviles-Olmos I, Dickson J, Kefalopoulou Z, Djamshidian A, Ell P, Soderlund T, Whitton P, Wyse R, Isaacs T, Lees A, Limousin P, Foltynie T.
Journal: J Clin Invest. 2013 Jun;123(6):2730-6.
PMID: 23728174     (This study is OPEN ACCESS if you would like to read it)

The researchers running the clinical study gave Exenatide to a group of 21 patients with moderate Parkinson’s disease and evaluated their progress over a 14 month period (comparing them to 24 control subjects with Parkinson’s disease). Exenatide was well tolerated by the participants, although there was some weight loss reported amongst many of the subjects (one subject could not complete the study due to weight loss). Importantly, Exenatide-treated patients demonstrated improvements in their clinician assessed PD ratings, while the control patients continued to decline.

Importantly, in a two year follow up study – this was 12 months after the patients stopped receiving  Exenatide – the researchers found that patients previously exposed to Exenatide demonstrated a significant improvement (based on a blind assessment) in their motor features when compared to the control subjects involved in the study.

The results of this initial clinical study are intriguing and exciting, but it is important to remember that the study was open-label: the subjects knew that they were receiving the drug. This means that we can not discount the placebo effect causing some of the beneficial effects reported.

There is, however, a follow up double blind clinical study currently underway – funded by the Michael J Fox Foundation – which will be completed in June of this year (2016).

We look forward to reading the results of that trial.

And Exenatide is not the only diabetes drug being tested

Pioglitazone is another licensed diabetes drug that is now being tested in Parkinson’s disease. It reduces insulin resistance by increasing the sensitivity of cells to insulin. Pioglitazone has been shown to offer protection in animal models of Parkinson’s disease (click here and here for more on this). And the drug is currently being tested in a clinical trial.

We look forward to reading these results as well.

Summing up

As with melanoma and red hair, there appears to be a curious connection between diabetes and Parkinson’s disease. Large longitudinal studies point to people with diabetes as having a higher risk of Parkinson’s disease than non-diabetic individuals. Why this is remains unclear, but some of the drugs used for treating diabetes may provide novel therapeutic options in the treatment of Parkinson’s disease. We will continue to follow this research and report results as they come to hand.

And you didn’t believe me about the monster saliva!