Treatment options for Parkinson’s disease through advancements in technology
This article is dedicated to my dad, who bravely fought the debilitating effects of Parkinson’s Disease for over a decade and passed away in 2020. It is in neuroscience and related emerging technologies that we can hope to find a cure and limit suffering for the 10 million+ people worldwide who are diagnosed.
What is Parkinson’s Disease?
Parkinson’s disease (PD) is a progressive disease that affects the brain and nervous system. There are several debilitating symptoms, the most common ones being: tremors (that are worse at rest), muscular rigidity, postural impairment, slow imprecise movements; and non-motor symptoms including cognitive impairment, memory loss and mood disorders (depression). PD most commonly affects men over the age of 50. The cause of PD is still unknown — although age, environment and genetics are thought to be leading factors. People with PD develop a dysfunction and degeneration of cell death in the basal ganglia (a group of structures involved with movement among others) of the midbrain, and a deficiency of the chemical dopamine. There are 5 stages of PD; how fast the symptoms intensify varies from person to person with no known cure.
According to Dr. Ray Dorsey, a neurologist at the University of Rochester Medical Center “Parkinson’s is already the fastest-growing neurological disorder in the world; in the U.S., the number of people with Parkinson’s has increased 35% the last 10 years. We think over the next 25 years it will double.”
Dopamine
In PD, certain nerve cells that send and receive signals from the brain (neurons) gradually break down or die. Many of the symptoms are due to a loss of neurons that produce a chemical messenger in the brain called dopamine. Dopamine is a neurotransmitter — a chemical that acts as a messenger between brain cells and is important for many of our daily functions. It has control over movements that are involved in muscle coordination, as well as arousal, positive & negative reinforcement, motivation, reward and emotional responses. When dopamine levels decrease, it causes abnormal brain activity, leading to impaired movement and other symptoms of PD.
There are two tiny strips of tissue which produce dopamine in the basal ganglia at the base of the brain called the substantia nigra and ventral tegmental areas. Combined, they are about the size of a postage stamp.
Understanding The Brain
Before looking at solutions, we need to have a brief tour of the brain. Neurons send and receive information and generally have three parts: a dendrite which receives a signal, a cell body called a soma which computes the signal, and an axon which sends out a signal.
The neurons of the brain connect to each other to send and receive signals through axon-dendrite connections called synapses. There is a small gap — called the synaptic cleft — between the axon of the ‘sending’ neuron and the dendrite of the ‘receiving’ neuron. Neurotransmitters float around in this space. There are many factors that affect neurotransmission (such as availability, agonist/antagonist presence, and re-uptake rate). Simply having the neurotransmitter released from the axon does not mean a successful action potential will be generated.
Understanding neurons in more depth: Synapses and Action Potential
Synapses are the junctions between the ends of two nerve cells (neurons). Signals are passed along the nerve cells in the form of an electrical impulse. When the impulses reach the synapses, they are transmitted from one nerve cell to the next by the use of specialized chemicals, called neurotransmitters, that cross the synaptic gap.
“Action potentials” are electrical events that cause synapses to release neurotransmitters. These neurotransmitters, bind to receptors on dendrites, opening channels that cause current to flow across the neuron’s membrane. When a neuron receives the ‘right’ combination of spatiotemporal (ie. at a certain time, at a certain place) synaptic input — and of sufficient magnitude — an action potential is initiated.
Parkinson’s Disease Diagnosis
There is no single test that exists for doctors to diagnose PD. The early stages of PD are hard to recognize as the motor symptoms are subtle. The best option is to see a neurologist (trained in movement disorders) when any irregularities in movement are noticed. Researchers have found that by the time motor symptoms occur (like a tremor), over 60% of all dopamine neurons in the basal ganglia of the brain have already been damaged — making it hard to treat.
A recently approved brain imaging technology called DaTscan can help people differentiate essential tremor (ET) versus the tremor due to Parkinson’s disease.
Current Traditional Treatments
The most common treatment for PD involves an attempt to restore depleted dopamine levels in the basal ganglia. Because dopamine does not cross the blood brain barrier, dopamine cannot simply be administered to a patient. Instead, patients can be given a precursor to dopamine called L-DOPA, in combination with another drug called Carbidopa. These drugs have been the primary treatment for PD since the 1960s. L-DOPA can cross the blood brain barrier and is used by the brain to synthesize more dopamine. This can lead to improvement in the motor symptoms of PD, but L-DOPA and Carbidopa do not halt the neurodegeneration that occurs in PD, and long term use causes a number of (potentially serious) side effects. These side effects in some cases outweigh the benefit of the medication.
These drug therapies are not a cure for the disease but rather slow it down and help to alleviate symptoms.
Emerging Technology for Treating Parkinson’s
There are some exciting new advancements in neuroscience and robotics that can help improve the quality of life for those living with Parkinson’s disease, and possibly even find a cure.
“To me, hope is informed optimism.” — Michael J. Fox
Could Stem Cells Cure Parkinson’s?
A major breakthrough in stem cell research for Parkinson’s is giving hope that a cure is on the horizon. Researchers working with laboratory rats have shown it is possible to make dopamine cells from embryonic stem cells and transplant them into the brain, replacing the cells lost to the disease.
Human embryonic stem cells, the precursor cells that have the potential to become any cell of the body — are a promising new generation of dopamine cells, that behave like native dopamine cells.
The new cells show all the properties and functions of the dopamine neurons that are lost in PD, and the potentially unlimited supply sourced from stem cell lines opens the door to clinical application. The next step is to prepare for human clinical trials.
“These cells have the same ability as the brain’s normal dopamine cells to not only reach, but also to connect to their target area over longer distances. This has been our goal for some time, and the next step is to produce the same cells under the necessary regulations for human use.” — Professor Parmar, Lund University Developmental and Regenerative Neurobiology
Deep Brain Stimulation
Deep brain stimulation is a surgical procedure that involves implanting electrodes in the brain, which deliver electrical impulses that block the abnormal activity that cause symptoms.
This surgery involves the placement of an implanted pulse generator (IPG) in the chest, which sends electrical impulses to specific areas of the brain through electrodes implanted below the scalp and inserted through the skull. The electrodes provide continuous electrical stimulation, which block the signals that cause the tremors of PD. There is currently over a 3 year wait list for this procedure in Canada.
Neuralink: The Future of Neural Engineering
The team behind Neuralink, led by Elon Musk, is creating a trailblazing brain machine interface system (BMI). The goal is to control machines with the power of thinking and solve neurological disorders like PD. With that in mind, in July 2019 Neuralink developed ultrafine ‘threads’ (the width of a human hair) that can robotically be woven into areas of the brain that control movement. The threads contain electrodes for detecting neural signals, connecting them to an implant called the Link.
Neuralink has also built a robotic system that can perform the intricate surgery to accurately insert these threads exactly where they need to be, under the supervision of a neurosurgeon. The goal is for it to become a non-invasive day procedure — similar to how lasik eye surgery is carried out.
Here is an April 2021 video of a monkey playing a video game from an implanted brain Link.
This BMI technology has the potential to restore brain functionality for a wide range of chronic and life-limiting motor neuron disorders including PD. It is intended to become accessible to the masses, essentially turning humans into cyborgs that can achieve symbiosis with artificial intelligence.
Focused Ultrasound
In 2018, the FDA approved the focused ultrasound (FUS) for treating PD tremors and potential restore brain functionality. FUS is an early-stage, non-invasive, therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients with PD. Doctors use MRI brain scans to direct ultrasound beams targeting the affected deep brain areas without damaging surrounding tissue. There is a thermal disruption of the tissue disrupting the blood-brain barrier (BBB) which can allow the desired therapeutics to enter the brain. Opening the BBB can also enable undesired materials to more easily leave the brain. FUS decreases symptoms immediately and is done when the patient is awake, not requiring surgery. FUS is only administered to only one side of the brain, is irreversible and permanent.
Psychedelic Treatments
In a press release on May 4, 2021 PharmaTher Holdings Ltd. announced it submitted an Investigational New Drug application with the US FDA. This was for a Phase 2 clinical trial of a groundbreaking solution to treat levodopa-induced dyskinesia (involuntary rapid movements) and pain management in PD patients, through a low-dose ketamine treatment. Other companies that are involved in R&D of psychedelic treatments for PD include: Compass Pathways, Seelos Therapeutics and Cybin Inc.
CBD (cannabidiol) is a chemical compound derived directly from the hemp plant. CBD taken in oil form in the early stages of PD can help manage symptoms.
Gyro Glove: Stabilizing Life
The Gyro Glove is the invention of a medical student who refused to accept that nothing could be done for PD patients. He turned to physics for an answer and found it in the mechanics of gyroscopes. Similar to a child’s toy top, gyroscopes are able to conserve angular momentum by countering any input of force in any direction quickly and proportionately.
Assistive technology is offering genuine hope to PD patients, giving them the chance to maintain a normal, independent life for much longer.
The prototype has shown a 90% reduction in tremors, using a miniature gyroscope to resist hand movement. It works by pushing back against the wearer’s movements as the gyroscope works to remain upright.
Exopulse Mollii Suit
A Swedish engineering team from startup Exoneural Network has invented a new suit to help improve mobility for neurological disorders. The medical suit for neuromodulation combines of a pair of pants, a jacket and a detachable remote control. There are 58 embedded electrodes in the suit that are adjusted to the wearer’s needs throughout the day.
Low-frequency electro stimulation (FES) improves blood circulation and restores previously inhibited balance between muscle pairs. For example, if the bicep is tensed, the suit would stimulate the antagonist muscle group, causing the bicep to relax.
Clinical studies are ongoing at universities and hospitals around the world.
A Holistic Approach
In addition to developments in neuroscience and robotics treatments, there are several lifestyle changes that can help manage PD symptoms. For example, despite my dad’s body and mind gradually deteriorating due to PD, I truly believe he added at least 2–3 years to his life by being very disciplined in his approach to daily life. Spending time outside, being active/exercising when possible, doing crossword puzzles for maintaining mind agility, getting regular massages to help with stiff/spastic muscles, staying socially connected and following a healthy diet (removing caffeine, sugar & alcohol) have proven to improve overall quality of life.
Hopefully the advancements in technology will unlock a cure and ease the pain that comes with this slow onset and unrelenting neurological disease.
