Genetic variations in a region of our DNA called PARKIN is associated with an increased risk of developing Parkinson’s – particularly young-onset PD (diagnosed before the age of 40yrs).
This area of DNA provides the instructions for making a protein (also referred to as PARKIN), which plays a number of important roles inside of cells.
Recently, a South Korean biotech company called Cellivery has published research on an experimental therapeutic agent that easily penetrates both the brain and cells within, delivering PARKIN protein to the cells that need it.
In today’s post, we will discuss what PARKIN does, review the new research report, and explore what could happen next.
Here on the SoPD we often talk about research regarding the prominent Parkinson’s associated proteins, think of alpha synuclein, LRRK2 and GBA. And they are of interest as there is a great deal of activity now at the clinical level exploring agents targetting these proteins.
But there are a number of interesting therapeutics being developed that are exploring some of the other Parkinson’s-associated proteins.
A good example was published this week:
Title: Intracellular delivery of Parkin rescues neurons from accumulation of damaged mitochondria and pathological α-synuclein
Authors: Chung E, Choi Y, Park J, Nah W, Park J, Jung Y, Lee J, Lee H, Park S, Hwang S, Kim S, Lee J, Min D, Jo J, Kang S, Jung M, Lee PH, Ruley HE & Jo D
Journal: Science Advances, 29 Apr 2020:6, 18, eaba1193
In this study, South Korean researchers demonstrated that a brain penetrating compound (including the PARKIN protein) can rescue numerous models of Parkinson’s.
Hang on a second: What is PARKIN?
The contents of today’s post may not be appropriate for all readers. An illegal and potentially damaging drug is discussed. Please proceed with caution.
3,4-Methylenedioxymethamphetamine (or MDMA) is more commonly known as Ecstasy, ‘Molly’ or simply ‘E’. It is a controlled Class A, synthetic, psychoactive drug that was very popular with the New York and London club scene of the 1980-90s.
It is chemically similar to both stimulants and hallucinogens, producing a feeling of increased energy, pleasure, emotional warmth, but also distorted sensory perception.
Another curious effect of the drug: it has the ability to reduce dyskinesias – the involuntary movements associated with long-term Levodopa treatment.
In today’s post, we will (try not to get ourselves into trouble by) discussing the biology of MDMA, the research that has been done on it with regards to Parkinson’s disease, and what that may tell us about dyskinesias.
Good times. Source: Carwash
You may have heard this story before.
It is about a stuntman.
His name is Tim Lawrence, and in 1994 – at 34 years of age – he was diagnosed with Parkinson’s disease.
Tim Lawrence. Source: BBC
Following the diagnosis, Tim was placed on the standard treatment for Parkinson’s disease: Levodopa. But after just a few years of taking this treatment, he began to develop dyskinesias.
Dyskinesias are involuntary movements that can develop after regular long-term use of Levodopa. There are currently few clinically approved medications for treating this debilitating side effect of Levodopa treatment. I have previously discussed dyskinesias (Click here and here for more of an explanation about them).
As his dyskinesias progressively got worse, Tim was offered and turned down deep brain stimulation as a treatment option. But by 1997, Tim says that he spent most of his waking hours with “twitching, spasmodic, involuntary, sometimes violent movements of the body’s muscles, over which the brain has absolutely no control“.
And the dyskinesias continued to get worse…
…until one night while he was out at a night club, something amazing happened:
“Standing in the club with thumping music claiming the air, I was suddenly aware that I was totally still. I felt and looked completely normal. No big deal for you, perhaps, but, for me, it was a revelation” he said.
His dyskinesias had stopped.
The world today is mourning the passing of the boxing great, Cassius Clay jr (aka Muhammad Ali). He was many different things to many different people – a boxer, an entertainer, a civil rights activist, an anti-war protestor, a philanthropist, a legend – but he was definitely one of the defining figures of the late 20th century.
During the last third of his life, however, he lived with Parkinson’s disease. You will find a great deal written about Ali and his sporting achievements elsewhere on the web, but today’s post here at SoPD will explore his battle with Parkinson’s.
Many famous figures throughout history have been affected by Parkinson’s disease ( Pope John Paul II, Adolf Hitler, Mao Zedong,…), but very few of them have dealt with their condition in the public eye as much as Muhammad Ali.
Ali was first diagnosed with Parkinson’s disease in 1984.
It was in September of that year – just three years into retirement from boxing – that Ali became concerned about tremors, slowness of movement, slurred speech and unexplained fatigue. He travelled with his entourage to New York, and he was evaluated for a week by Dr Stanley Fahn, M.D., a neurologist at Columbia-Presbyterian Medical Center (New York), before Fahn finally gave Ali his diagnosis.
Dr Stanley Fahn. Source: Youtube
Given his long boxing career, Dr. Fahn suspected that the head trauma inflicted on Ali could be the cause of his condition. In fact, one of the early complaints from Ali was of numbness in his lips and face, which Dr Fahn assumed meant damage to the brain stem – most likely resulting from the boxing.
Neurodegeneration is a serious issue for boxing. Many retired boxers suffer from what is called Dementia pugilistica – a neurodegenerative condition with Alzheimer’s-like dementia. Some estimates suggest that 15-20% of boxers may be affected, with symptoms usually starting 12-16 years after the start of a career in boxing. Some very famous boxers have been diagnosed with this condition, including world champions Floyd Patterson, Joe Louis, Sugar Ray Robinson and boxer/coach Freddie Roach.
In the case of Ali, however, subsequent follow up assessments over many years highlighted the steady progression of his condition, a disease course more indicative of classic Parkinson’s disease. Dr. Fahn admits, however, that – as with all cases of Parkinson’s disease – “the proof is only going to come at his autopsy”.
Ali and a young fan. Source: Pinterest
Being diagnosed at 42 years of age basically placed Ali in the ‘young onset’ group of people with Parkinson’s disease. The average age of diagnosis for Parkinson’s disease is 65 years, but 5-10% of the Parkinson’s community is diagnosed at or below the age of 40. And there are many anecdotal bits of evidence to suggest that Ali was possibly affected by the disease before the age of 40. Ali’s trainer, Angelo Dundee, suspected that Ali’s condition was present during the last few years of his boxing. He remembers Ali gradually slowing down and the newspaper reporters having to lean in to hear what Ali was saying during some of the later interviews. Sports Illustrated senior writer William Nack also noted that “You could see back then that he was just not right”. So although Ali was diagnosed at 42 years of age, the condition may have been affecting him much earlier.
Following the diagnosis, Ali stepped away from the public eye. Parkinson’s affected both of Ali’s most defining characteristics: his moves and his voice. It would have been very understandable for a man as proud as Ali to decide to disappear completely while dealing with his condition. A decade later, however, Ali lit the Olympic caldron at the opening ceremonies of the Atlanta Games (1996), and he was rarely out of the public eye. Attending regular events not only in support of Parkinson’s disease, but also in his role of globetrotting ambassador for peace. Within the Parkinson’s community, Ali lent his name to the ‘Muhammad Ali Parkinson Research Center‘ (Phoenix) and also served as an ambassador for Parkinson’s causes.
In writing this post I have learned a great deal about Ali that I did not know. I have also enjoyed watching and re-watching many of the video interviews of Ali on the internet (Michael Parkinson’s ones are particularly good). Beyond everything the man did and the disease that later came to define him, Ali was an amazing character. It is difficult to think of his equal in the modern world of sports (or beyond).
Truly a sad day.
Inspirational words from the man. Source: Wallpapercave