Tag: ALS

Getting expansive about treg cells

~ Simon ~ 5 Comments

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In cancer research, scientists have devised methods of extracting samples of blood from patients and then growing certain populations of cells in those samples. The isolated subpopulations  of cells can then be manipulated in cell culture, before they are then injected back into the patient.

This is a form of immunotherapy – artificially boosting the immune system to target specific disease-related pathology in the body.

Recently, researchers have been exploring this alternative form of immunotherapy in the context of Parkinson’s… with some interesting results.

In today’s post, we will look at review this new research and consider the implications in terms of future therapies for Parkinson’s.

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Source: lls

Some time back, a friend in oncology (cancer) research said to me that “we are about to cure all blood cancers“. It should be noted that this optimistic friend is a “glass is completely full” type.

“How so?” I asked.

“CAR T-cell technology is amazing. Really coming into bloom” they responded.

“What is CAR T-cell technology?” I asked.

They explained that it is a kind of immunotherapy – a method of boosting the immune system to help us fight disease.

CAR T-cell approaches basically involve removing a sample of blood from a person with cancer, expanding specific populations of those cells in cell culture, genetically manipulating those cells, and then re-introducing them into the body. They also explained that there were lots of different versions of CAR T-cells, with all kinds of potential applications.

“Cool” I said, sounding enthusiastic, but only half understanding what they were saying. My friend is an immunologist, and my summary here is a one sentence version of a 30 minute sermon.

But they are correct.

CAR T-cell technology is achieving really impressive results in cancer (Click here and here to read more about this topic).

Interesting. What does this have to do with Parkinson’s?

Continue reading “Getting expansive about treg cells” →

When miro just can’t let go

~ Simon ~ 20 Comments

 

Stanford University researchers have recently published an interesting report in which they not only propose a novel biomarker for Parkinson’s, but also provide some compelling data for a novel therapeutic approach.

Their research focuses on a protein called Miro, which is involved in the removal of old or faulty mitochondria. Mitochondria are the power stations of each cells, providing cells with the energy they require to do what they do.

Specifically, the researchers found that Miro refuses to let go of mitochndria in people with Parkinson’s (which could act as a biomarker for the condition). They also found that pharmacologically forcing Miro to let go, resulted in neuroprotective benefits in models of Parkinson’s

In today’s post, we will discuss what Miro is, what the results of the new research suggest, and we will consider what will happen next.

 

 

Source: Amazingaccelerators

Every now and then a research report comes along and you think: “Whoa, that’s amazing!”

It a piece of work that breaks down your cynicism (which you have proudly built up over years of failed experiments) and disciplined scepticism (a critical ingredient for a career in scientific research – mantra: ‘question everything’). And for a moment you are taken in by the remarkable beauty of not just good research, but biology itself.

A couple of weeks ago, one such research report was published.

This is it here:

Title: Miro1 Marks Parkinson’s Disease Subset and Miro1 Reducer Rescues Neuron Loss in Parkinson’s Models.
Authors: Hsieh CH, Li L, Vanhauwaert R, Nguyen KT, Davis MD, Bu G, Wszolek ZK, Wang X.
Journal: Cell Metab. 2019 Sep 23. [Epub ahead of print]
PMID: 31564441

It’s a really interesting study for several reasons.

So what did they report?

Continue reading “When miro just can’t let go” →

“Transdiagnostic” clusters

~ Simon ~ 7 Comments

 

“In current models of neurodegeneration, individual diseases are defined by the presence of one or two pathogenic protein species. Yet, it is the rule rather than the exception that a patient meets criteria for more than one disease”

These are the first lines of a manuscript on the preprint sharing webiste BioRxiv, which analysed the co-occurance of biological markers of Alzheimer’s or Parkinson’s or other neurodegenerative conditions across 18 brain regions in 1389 postmortem brain from people who passed away with a neurodegenerative condition.

The results are interesting.

In today’s post, we will discuss what this study did, what is meant by “transdiagnostic disease clusters”, and consider what could they mean for our understanding of Parkinson’s… and heck, neurodegenerative conditions in general.

 

Malcolm Gladwell. Source: Masterclass

I am a fan of Malcolm Gadwell (not an endorsement, this is just me sharing).

He has a great way of looking at a situation from a completely different angle, finding things that no one else sees, and then writing about it in a clever, easy to read manner. Having read most of his books, I was rather pleased to learn that he has a podcast – Revisionist History.

And it’s good.

Oh boy, it’s good.

The first episodes of the most recent series of the podcast have helped to raise my fragile self esteem, because I am definitely a tortoise (just listen to the first two episodes of season 4 and you’ll understand).

Oh, and Mr Gladwell, if you ever read this – in the next series of the podcast, please have a look at the dysfunctional way we clinically test new therapies in medicine – click here to read a previous SoPD rant on this topic. Thanks!

What does Malcolm Gladwell have to do with Parkinson’s?

It all comes back to that idea of looking at a situation from a completely different angle.

What do you mean?

Continue reading ““Transdiagnostic” clusters” →

Making sense of antisense

~ Simon ~ 11 Comments

 

Recent regulator approvals and exciting new preclinical data has refocused attention on a treatment approach for genetic conditions that has travelled a long and winding road towards clinical use.

Antisense oligonucleotides represent a method of altering protein levels at the post transcriptional level – it basically stops certain RNAs from being translated into protein.

And recently, a new clinical trial has been registered which will explore the use of this treatment approach in people with Parkinson’s.

In today’s post, we will look at what antisense oligonucleotides are, how they work, what research has been conducted in the context of Parkinson’s, and some of the limitations of this approach that still exist.

 

Source: Youtube

Spinal muscular atrophy (or SMA) is a genetic disorder that results in the degeneration of motor neurons in the spinal cord. This leads to progressive weakening and atrophy of muscules, ultimately leaving sufferers paralysed. It is caused by loss-of-function mutations in the survival motor neuron 1 (SMN1) gene.

It is a terrible condition that starts in very young children and has an incidence approaching 1:10,000 live births.

Luckily, novel therapies are being developed to deal with this condition, and in 2016, the US FDA approved a new treatment – following rather dramatic clinical trial results – called Nusinersen. This new therapy has caused a great deal of excitement as it basically halted the progression of SMA in many cases.

And a recent long term report highlights some of these very impressive results:

Title: Nusinersen in later-onset spinal muscular atrophy: Long-term results from the phase 1/2 studies.
Authors: Darras BT, Chiriboga CA, Iannaccone ST, Swoboda KJ, Montes J, Mignon L, Xia S, Bennett CF, Bishop KM, Shefner JM, Green AM, Sun P, Bhan I, Gheuens S, Schneider E, Farwell W, De Vivo DC; ISIS-396443-CS2/ISIS-396443-CS12 Study Groups.
Journal: Neurology. 2019 May 21;92(21):e2492-e2506.
PMID: 31019106                (This report is OPEN ACCESS if you would like to read it)

Most importantly, Nusinersen is having real impact on the children who are affected by this condition:

Interesting, but what exactly is Nusinersen?

It is an antisense oligonucleotide.

What are antisense oligonucleotides?

Continue reading “Making sense of antisense” →

Denali: Phase Ib clinical trial starts

~ Simon ~ 15 Comments

 

Biotech firm Denali announced the dosing of the first person in their Phase Ib clinical study of their experimental treatment for Parkinson’s called DNL201.

DNL201 is an inhibitor of a Parkinson’s-associated protein called Leucine-rich repeat kinase 2 (LRRK2).

In Parkinson’s, there is evidence that LRRK2 is over activate, and by inhibiting LRRK2 Denali is hoping to slow the progression of Parkinson’s.

In today’s post, we will discuss what LRRK2 is, what evidence exists for DNL201, and what the new clinical trial will involve.

 

 

Founded in 2013, by a group of former Genentech executives, San Francisco-based Denali Therapeutics is a biotech company which is focused on developing novel therapies for people suffering from neurodegenerative diseases. Although they have product development programs for other condition (such as Amyotrophic Lateral Sclerosis and Alzheimer’s disease), Parkinson’s is their primary interest.

And their target for therapeutic effect?

The Parkinson’s-associated protein called Leucine-rich repeat kinase 2 (or LRRK2).

What is LRRK2?

Continue reading “Denali: Phase Ib clinical trial starts” →

Mission: Not Impossible

~ Simon ~ 10 Comments

 

 

The SoPD has a policy of not advertising or endorsing products/services.

This rule is in place to avoid any ethical/conflict of interest situations. It does little, however, to stop folks from bombarding the comments sections with links for wondrous magical cures which probably involve more ‘magical’ than actual cure.

Having said all that, every now and then I find or read about something that I think may be of interest to readers. In many of those cases, I can not vouch for the information being provided, but where I think there is the potential to stimulate the imagination of the reader, I am happy to take a chance and share it.

Today’s post is all about one such case: Not impossible labs.

 

Source: mfah

The first character in this story is a graffiti artist.

His name is Tony ‘Tempt’ Quan.

Tempt grew up in east Los Angeles, painting his name and art across the city from the 1980s onwards. He became the stuff of myth and legend – one of the most influential figures in the graffiti scene in California for a generation.

Source: Reelhouse

But that all changed in 2003, when – at 34 years of age – Tempt was diagnosed with Amyotrophic Lateral Sclerosis (or ALS).

Also known as motor neurone disease or Lou Gehrig’s disease, ALS is a neurodegenerative condition that leaves the sufferer completely paralysed. There are only two FDA-approved drugs for the treatment of ALS, but they have little if any impact on disease course.

For 6 years, Tempt lay paralysed and did not produce a single piece of art.

And that was when the second character in this story appeared.

His name was Mick Ebeling.

Continue reading “Mission: Not Impossible” →

Ibudilast: A Phosphodiesterase inhibitor

~ Simon ~ 5 Comments

A reader recently asked me about an experimental drug called Ibudilast.

It is a ‘Phosphodiesterase 4 inhibitor’.

Recently there was a very interesting result in a clinical trial looking at Ibudilast in a specific neurodegenerative condition. Sadly for the reader that condition was not Parkinson’s, in fact very little research has been done on Ibudilast in Parkinson’s

In today’s post we will look at what Phosphodiesterase inhibitors are, how they work, and discuss why Ibudilast may not be such a good experimental treatment for Parkinson’s.

On April 21-27th, 2018, the American Academy of Neurology (AAN) will hold their 70th Annual Meeting in Los Angeles (California).

I will not be at the meeting, but I will definitely be keeping an eye out for any news regarding the results of one particular clinical trial. At the meeting, a biopharmaceutical company called MediciNova Inc. will be presenting data regarding one of their clinical trials.

The presentation, entitled “Ibudilast – Phosphodiesterase Type 4 Inhibitor – Bi-Modal Therapy with Riluzole in Early Cohort and Advanced Amyotrophic Lateral Sclerosis (ALS) Patients – Final Report and Future Directions“ (Source) will be presented by principal investigator of the clinical study, Dr. Benjamin Rix Brooks, of the Carolinas HealthCare System’s Neuromuscular/ALS-MDA Center at Carolinas HealthCare System Neurosciences Institute.

Dr Brooks will be presenting the results of a single-center, randomized, double-blind, placebo-controlled clnical trial which was conducted to evaluate the safety, tolerability and clinical endpoint responsiveness of a drug called Ibudilast (or MN-166) in subjects with the neurodegenerative condition, Amyotrophic Lateral Sclerosis (or ALS – also known as motor neuron disease; Click here to read a previous SoPD post about ALS and Click here to learn more about this clinical trial).

What is Ibudilast?

Ibudilast is a phosphodiesterase inhibitor.

What is a phosphodiesterase inhibitor?

Continue reading “Ibudilast: A Phosphodiesterase inhibitor” →

UDCA 2.0 = TUDCA?

~ Simon ~ 11 Comments

Ursodeoxycholic acid (UDCA) has been proposed as a drug that could be repurposed for Parkinson’s. As a medication, it is called ‘Ursodiol‘ and it is used to treat gallstones.

But there are absorption issues with UDCA: The passage of UDCA through the wall of the small intestine is slow and incomplete (Source).

There may be a solution, however, called Tauroursodeoxycholic acid (TUDCA). Think of it as UDCA-2.0. It is more easily absorbed by the gut. And there is also good evidence to suggest that it has the same beneficial neuroprotective properties as UDCA.

In today’s post we will discuss what exactly UDCA and TUDCA are, review the Parkinson’s research for both, and discuss why one of these drugs should be tested in the clinic for PD.

Gallstones – ouch! Source: Healthline

Let me introduce you to your gallbladder:

It is one of the less appreciated organs; a pear-shaped, hollow organ located just under your liver and on the right side of your body. Its primary function is to store and concentrate your bile. Bile is a yellow-brown digestive enzyme – made and released by the liver – which helps with the digestion of fats in your small intestine (the duodenum).

Source: Mayoclinic

Now, let me introduce you to your gallstones:

Gallstones are hardened deposits that can form in your gallbladder. About 80% of gallstones are made of cholesterol. The remaining 20% of gallstones are made of calcium salts and bilirubin. Bilirubin is the yellow pigment in bile. When the body produces too much Bilirubin or cholesterol, gallstones can develop.

About 10-20% of the population have gallstones (Source), but the vast majority experience no symptoms and need no treatment.

Interesting intro, but what does any of this have to do with Parkinson’s?

One of the treatments for gallstones is called UDCA. And this compound is being considered for “repurposing” as a treatment for Parkinson’s.

What is UDCA?

Continue reading “UDCA 2.0 = TUDCA?” →

Something is interesting in the state of Denmark

~ Simon ~ 5 Comments

 

 

Gaucher disease is a genetic disorder caused by the reduced activity of an enzyme, glucocerebrosidase. This enzyme is produced by a region of DNA (or a gene) called GBA – the same GBA gene associated with a particular form of Parkinson’s.

Recently, a Danish company has been testing a new drug that could benefit people with Gaucher disease.

It is only natural to ask the question: Could this drug also benefit GBA-associated Parkinson’s?

In today’s post, we will discuss what Gaucher disease is, how this experimental drug works, and why it would be interesting to test it in Parkinson’s.

Will Shakespeare. Source: Ppolskieradio

The title of this post is a play on words from one of the many famous lines of William Shakespeare’s play, Hamlet.

The original line – delivered by Marcellus (a Danish army sentinel) after the ghost of the dead king appears – reads: If the authorities knew about the problems and chose not to prevent them, then clearly something is rotten in the state of Denmark.

(Act 1, Scene 4)

The title of this post, however, is: Something is interesting in the state of Denmark

This slight change was made because certain Danish authorities know about the problem and they are trying to prevent it. The ‘authorities’ in this situation are some research scientists at a biotech company in Denmark, called Orphazyme.

And the problem is Parkinson’s?

No, the problem is Gaucher disease.

Huh? What is Gaucher disease?

Continue reading “Something is interesting in the state of Denmark” →

Higher socioeconomic status jobs

~ Simon ~ 11 Comments

o-INEQUALITY-GIF-facebook

People with high socioeconomic status jobs are believed to be better off in life.

New research published last week by the Centre for Disease Control, however, suggests that this may not be the case with regards to one’s risk of developing Parkinson’s disease.

In today’s post we will review the research and discuss what it means for our understanding of Parkinson’s disease.

childrenoflo

The impact of socioeconomic status. Source: Medicalxpress

In 2013, a group of researchers at Carnegie Mellon University found a rather astonishing but very interesting association:

Children from lower socioeconomic status have shorter telomeres as adults.

Strange, right?

Yeah, wow, strange… sorry, but what are telomeres?

Do you remember how all of your DNA is wound up tightly into 23 pairs of chromosomes? Well, telomeres are at the very ends of each of those chromosomes. They are literally the cap on each end. The name is derived from the Greek words ‘telos‘ meaning “end”, and ‘merοs‘ meaning “part”.

Telomeres are regions of repetitive nucleotide sequences (think the As, Gs, Ts, & Cs that make up your DNA) at each end of a chromosome. Their purpose seems to involve protecting the end of each chromosome from deteriorating or fusing with neighbouring chromosomes. Researchers also use their length is a marker of ageing because every time a cell divides, the telomeres on each chromosome gradually get shorter.

Continue reading “Higher socioeconomic status jobs” →