As everyone knows by now, boxing legend Muhammad Ali died this past weekend at the age of 74. He was an incredible fighter in the ring admired by millions. But for the past 32 years, Ali had also been locked in a match with Parkinson’s disease, a neurodegenerative disorder that affects about 1 million people in the United States. Ali worked as a tireless advocate to raise awareness of the disease and to establish a center that provides comprehensive care for those affected.
Parkinson’s is a result of the loss of cells in various parts of the brain, including one portion that produces the neurotransmitter dopamine. Dopamine is essential for being able to move in a coordinated way, so the loss of dopamine causes the tremors often associated with the condition.
While the exact cause of Parkinson’s is unknown, genetics and environment are contributing factors. Most cases occur in patients with no family history of Parkinson’s disease, but there are 13 gene mutations that have been linked to either causing the disease or increasing one’s risk of developing it. Certainly not everyone who carries these gene mutations develops Parkinson’s, but identifying these genetic indicators is the beginning of developing more precise treatments.
There are many risk factors linked to Parkinson’s. It’s unknown why, but men seem to be more often affected than women. Age is another factor. According to the Michael J. Fox Foundation, the biggest risk factor for Parkinson’s disease is advancing age. Despite that, some people can develop it as young as 30, but that’s less common – 2 percent of the million people with Parkinson’s disease are thought to be younger than 40 years old (Ali was diagnosed at age 42). There can be external risk factors as well, such as exposure to pesticides or traumatic brain injury caused by repeated blows to the head. Because of the early onset of Ali’s Parkinson’s, there is no agreement as to whether or not blows to the head from boxing were a factor.
There is no cure for Parkinson’s disease, but it’s also not a fatal ailment in itself. As the symptoms worsen, though, they can cause complications that lead to death. Pneumonia is the leading cause of death for those with Parkinson’s, because as motor skills deteriorate, it can affect a person’s ability to cough and swallow.
However, what the field of medicine currently knows about Parkinson’s and the available treatments are due in large part to the use of animal models.
The disease was first described in the early 1800s by James Parkinson, but it wasn’t until the 1950s that researchers were able to understand what may be happening in the brain.
Arvid Carlsson’s research with mice and rabbits showed that dopamine was instrumental in controlling walking and other voluntary movements, and that a depletion of this neurotransmitter impaired movement. When he gave the amino acid levodopa (L-DOPA) to animals with depleted dopamine, he found that they were able to move normally again. This later resulted in the use of L-DOPA in patients with Parkinson’s disease, and it remains one of the most widely-used treatments available for those affected by Parkinson’s.
However, like many current treatments for Parkinson’s disease, L-DOPA only treats the symptoms, and it can lose effectiveness as time goes on. But there is hope for those who do not benefit from L-DOPA, a treatment called deep brain stimulation (DBS).
In the 1980s, researchers studying monkeys were able to identify the area of the brain affected by this disease. While researchers identified the location, they did not know how it was affected.
Later, they discovered that lowered dopamine levels led to increased activity in the subthalamic nucleus (STN) which resulted in motor abnormalities in monkeys. By interfering with the STN, they could relieve the Parkinson’s symptoms. Eventually, researchers were able to find a better way to induce the effect of damage without permanently harming the brain by stimulating the STN at a high frequency, which stopped the activity that was causing abnormalities with movement, relieving the symptoms.
With DBS, a pacemaker is implanted that sends electrical impulses to the brain. In 2002, the Food and Drug Administration approved the use of DBS to help treat Parkinson’s.
While L-DOPA and deep brain stimulation are two of the most common treatments for Parkinson’s disease, they’re by no means the only ones, especially with considering more recent research. The Buck Institute has identified a new target for drugs to treat sporadic Parkinson’s disease. The same responses to stress that lead to neuronal cell death in mice bred to develop Parkinson’s also lead to cell death in the more common sporadic form of Parkinson’s disease. They found that oxidative stress affects the protein involved in degradation of damaged protein in the same way that genetic mutations do. By identifying this pathway, they hope that they will be able to figure out what compounds target the pathway and how to prevent the damage related to the disease. By targeting these compounds, researchers may be able to better treat Parkinson’s disease.
Based on his tireless advocacy, Muhammad Ali undoubtedly would have been supportive of this research. In fact, he and Michael J. Fox testified before Congress in 2002, highlighting the need to fund more Parkinson’s disease research. And while the world’s attention is at least momentarily focused on this dreadful disease, it is worth remembering that the treatments we have now may not have come to fruition without the help of mice, rabbits and monkeys. As researchers continue to strive for an Ali-style “knockout,” they will achieve it with the help of animal models and advocates alike.
Feature image courtesy of Dutch National Archives
My laboratory has been working with bacterial compounds from the gut that are strongly anti-inflammatory, readily pass thru the blood-brain barrier, and may reduce oxidative stress and associated inflammation within the central nervous system. I am looking for funding from agencies interested in this sort of approach and would like any leads you may be able to provide. Thanks in advance.
“Because of the early onset of Ali’s Parkinson’s, there is no agreement as to whether or not blows to the head from boxing were a factor.” It would seem to me that the 29,000 or so punches to his head would make early onset more likely.
Not to question Mr. Ali’s sincerity. But I wonder if he would oppose boxing, which is a risk factor for Parkingson’s. (Ref: https://www.statnews.com/2016/06/04/muhammad-ali-parkinsons-disease/). Boxing without competition therefore without head trauma is an excellent exercise; in fact, people practice it to fight the disease (http://www.cbsnews.com/pictures/fighting-parkinsons-with-boxing/). But with competition, boxing is an evil sport for the brain and beyond. (I remember the American Heart Association petitioned to ban this sport as early as 1970’s.)
I wasn’t aware monkeys and rabbits were part of this research. Someone close to me died of Parkinson’s, so I really really hope we can find a cure. I saw online it costs our healthcare system something like 14 billion dollars a year. We have to do something, and please act more quickly.
Mohammad Ali died last week (Innal laha wa inna ileyhe rajeoon). All boxers of Ali’s level have not developed PD, so punching may or may not be the underlying reason for Ali’ PD. PD is a neurodegenrative disease of the brain especially affecting basal ganglia (substantia nigera) and progress slowly resulting into debilitating condiction including no control on bowel and urination with cognitive impairment (dementia) and severe depression. Both progressive neuron degeneration and advancing age complement each other in causing complications and finally death.
Innovative ideas: A device containing dopamine and connected to substantia nigera automatically pumping dopamine when its level is low. Dopamine transplantation in the affected region in the brain. Stem cells, modified to produce dopamine, could also be transplanted into the affected areas of the brain. Finally gene therapy though there are no specific gene mutations. Long live Mohammad Ali and Almighty God (Allah) give him a place in heaven (Ameen). Dr. Naseem Akhtar Qureshi MD, PhD
Boxing is a form of exercise that helps fight Parkinson’s. I don’t know how could a famous boxer like Md. Ali had died of Parkinson’s disease.