Kirk's Blog

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Kirk started writing articles for his blog around the time his first book was published (September 2011). Not having any other bright ideas at the time, he adopted the book title as his “brand” for the blog. Over time, Shaky Paws Grampa (SPG) has become his “identity” in the PD world. The good news is that he hasn’t had to fight anybody for it and there was no competition for the web address (understandably).

He didn’t have any clear goals in mind for the blog when he started other than to make his target audience the “PD world”, opting to write about what ever inspired him at the moment. Over time, various themes emerged:

Book or writing-related
PD-related information
Clinical research study advocacy/participation
Cognition issues
Living with PD-personal
PD meeting/conference announcements
SPG speaking engagements, media interviews, and webinars
Calls to action
Personal

Three years later, he has posted 120 articles that have been viewed by readers from over 60 countries around the world.

PARKINSON’S & GENETIC ENGINEERING

 

I am a PwP (person with Parkinson’s) who is very interested in the topic of genetic engineering in general, but specifically with regard to neurodegenerative diseases and especially Parkinson’s. I am going to provide a number of links from the internet related to this topic and also discuss new developments.

1.  Gene therapy breaking ground in treating Parkinson’s disease

https://www.geneticliteracyproject.org/2016/08/23/gene-therapy-breaking-ground-treating-parkinsons-disease/

           
           

Parkinson’s patients who take the drug levodopa, or L-Dopa, are inevitably disappointed…[when,] over time[,] the drug becomes less effective…

A biotech company called Voyager Therapeutics now thinks it can extend the effects of L-Dopa by using a surprising approach: gene therapy. The company…is testing the idea in Parkinson’s patients who’ve agreed to undergo brain surgery and an injection of new DNA.

Voyager’s strategy…is to inject viruses carrying the gene for AADC into the brain, an approach it thinks can “turn back the clock” so that L-Dopa starts working again in advanced Parkinson’s patients as it did in their honeymoon periods.

[There is] one edge [that] Voyager’s approach has over others. It is possible to tag AADC with a marker chemical, so doctors can actually see it working inside patients’ brains…[In] past studies of gene therapy, by contrast, doctors had to wait until patients died to find out whether the treatment had been delivered correctly.

“I believe that previous failure of gene-therapy trials in Parkinson’s was due to suboptimal delivery,” says [Krystof] Bankiewicz.

Complete article: https://www.technologyreview.com/s/602193/manufacturing-dopamine-in-the-brain-with-gene-therapy/

2.Scientists genetically engineer world’s first monkey with Parkinson’s disease

http://parkinsonslife.eu/scientists-genetically-engineer-worlds-first-monkey-with-parkinsons-disease/

Controversial research hopes to “predict the onset of symptoms”


It might sound all a bit Frankenstein. But it’s true – researchers have genetically modified the world’s first monkey to have Parkinson’s disease. The controversial development will provide unique insight for scientists and could lead to major breakthroughs for people living with the disease.

The research team from Japan presented their marmoset model of Parkinson’s at the State of the Brain meeting in Austria last month. Led by Professor Hideyuki Okano of the Keio University School of Medicine in Tokyo, the researchers developed the marmosets to have mutated copies of a human gene called SNCA that is linked to Parkinson’s, according to The New Scientist.

When the SNCA gene becomes ‘faulty’, alpha-synuclein – the protein that kills the dopamine-making cells – builds up in the brain. It’s this lack of dopamine that causes the motor symptoms experienced by Parkinson’s patients.

The first signs of Parkinson’s symptoms began to manifest in the monkeys three years after birth. First they displayed signs of sleep disturbance, and later their brain stems began to display instances of protein globules composed of alpha-synuclein called Lewy bodies – a strong indicator of Parkinson’s. This was followed by characteristic tremors associated with the condition.

The brains of primates are a lot more similar to ours than those of mice, which currently dominate the neurological field of research. Okano’s team showed that when treated with levodopa, the tremors in the monkeys were alleviated in the same way humans react to the drug.

The scientists hope that this research using brains similar to our own will lead to new treatments. “With these diseases, it’s very difficult to investigate what’s happening in living people, so knowledge of the brain circuits responsible are mostly unidentified,” says Okano. “We hope to find ways to predict the onset of each symptom, and develop drugs to slow down disease progression.”

While primate research is generally met with public disapproval in Europe and the US, opposition in Japan and China is less prevalent where breeding colonies house thousands of primates for scientific research.

3.  Discovery of genetic 'switch' could help to prevent symptoms of Parkinson's disease. https://www.sciencedaily.com/releases/2017/02/170217100054.htm

In a paper published in the journal Cell Death and Differentiation, the team discovered that a gene called ATF4 plays a key role in Parkinson's disease, acting as a 'switch' for genes that control mitochondrial metabolism for neuron health.

Dr Miguel Martins from the MRC Toxicology Unit at the University of Leicester, who led the research, explained: "When the expression of ATF4 is reduced in flies, expression of these mitochondrial genes drops. This drop results in dramatic locomotor defects, decreased lifespan, and dysfunctional mitochondria in the brain.

"Interestingly, when we overexpressed these mitochondrial genes in fly models of Parkinson's, mitochondrial function was reestablished, and neuron loss was avoided."

By discovering the gene networks that orchestrate this process, the researchers have singled out new therapeutic targets that could prevent neuron loss.

Some forms of Parkinson's are caused by mutations in the genes PINK1 and PARKIN, which are instrumental in mitochondrial quality control.

Fruit flies with mutations in these genes accumulate defective mitochondria and exhibit Parkinson's-like changes, including loss of neurons.

The researchers used PINK1 and PARKIN mutant flies to search for other critical Parkinson's genes -- and using a bioinformatics approach discovered that the ATF4 gene plays a key role.

Dr Martins added: "Studying the roles of these genes in human neurons could lead to tailored interventions that could one day prevent or delay the neuronal loss seen in Parkinson's."

The findings build upon recent research by the University of Leicester team, which recently discovered several genes that protect neurons in Parkinson's disease, creating possibilities for new treatment options.

Two of the genes -- PINK1 and PARKIN -- affect how mitochondria break down amino acids to generate nucleotides -- the metabolism of these molecules generates the energy that cells need to live.

Thoughts

I am not a doctor or scientist, so any comments I make are from an (interested and at least somewhat informed) layman perspective.

These three articles cover different topics but seem to be related to what is, ultimately, genetic engineering. The first involves introduction of a virus containing a healthy gene with the goal of having it replace the patient’s defective gene with one that will enhance the effectiveness of dopamine they are taking, thus reducing symptoms to a level associated with a much earlier stage of the disease. It is not clear to what degree this would be a “long term fix”, but the process includes a “marker” that would make it possible to evaluate changes.

The second article is one example of potential ethical issues connected to genetic engineering. The topic is marmosets that are genetically engineered to have PD for the purpose of research.

The third article discusses genetic manipulation of fruit flies and the discovery of a gene called ATF4 that has been altered in studies that result in a decrease in PD symptoms in the flies.

To be clear, gene therapy is not new news. There have been studies that have shown mixed results. Researchers have told me that, based on results to date, they don’t it as holding much promise.

In the last six months or so there has been a great deal of news surrounding a genetic engineering technology called CRISPR that seems extremely promising. I recommend reading this article (http://sitn.hms.harvard.edu/flash/2016/crispr-in-neuroscience-how-precision-gene-editing-may-unravel-how-the-brain-works-and-why-it-sometimes-doesnt/) for a detailed discussion about what it is, how it works, and the dramatic implications it holds for neuroscience

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