Recently, many effective treatments were just a dream, but innovators created them and pioneers implemented them. And this is just the beginning. Stay with us, and you’ll be the first to learn about new treatments that will change the future. We are together on this journey — towards health, hope, and victory.
Examples of victories over other diseases inspire: we can conquer this one too! Read about strategies that will help in the fight against Parkinson’s, and believe — support is already near.
Attention, there are treatments from the past and future that are either already or not yet in use! Consult a specialist.
Parkinson’s disease is a complex issue because it gradually impairs brain function, and current treatments cannot completely stop or cure it. Medications and surgical treatments, such as deep brain stimulation and radiofrequency ablation (thalamotomy), and state-of-the-art MRI-guideded focused ultrasound treatment help manage symptoms, but scientists are working on new ways to slow the disease’s progression, restore damaged cells, or better control its signs.
Before the advent of modern treatment methods, Parkinson’s disease was treated in various ways based on the available knowledge of the time.
There are also quite “ancient ” treatment methods that were previously prescribed for many other diseases
- Bloodletting: This method was used for “blood purification ” and relieving tension in the body
- Opiates: Sometimes used to alleviate tremor and other symptoms.
Since ancient times, people have used treatments that are still used today for Parkinson’s disease:
- Physical exercise and massage — to reduce muscle stiffness and improve mobility
- Physical Activity: Patients were advised to move more to reduce stiffness and improve coordination.
- Diet and Herbs: Special diets and herbal remedies were used, which were considered beneficial for the nervous system, and it was assumed that nutrition could affect the symptoms.
Before George Cotzias introduced revolutionary treatment for Parkinson’s disease using high doses of levodopa, doctors tried various methods. These approaches were often based on a limited understanding of the nature of the disease, but each contributed to the development of medicine. Here are the main ones:
- Metals : Mercury and iron subcarbonate were used as medicinal agents. However, their effectiveness was questionable, and they could cause side effects.
- Herbal Medicines : Doctors used rye ergot and belladonna. Belladonna, containing alkaloids, had a certain calming effect and became a popular remedy for many decades; it was used to alleviate tremor because it contains atropine (these drugs are not the main treatment now)
- Chemical substances : Tried chloroform and strychnine. However, strychnine sometimes worsened the condition of patients, and its use was subsequently discontinued.
- Galvanization : In 1855, Duchenne introduced the method of electrotherapy, called galvanization, into medicine. It was assumed that electric current could improve symptoms, but the results were contradictory.
- Vibration therapy : Jean-Martin Charcot, a renowned neurologist, noted that vibrations can temporarily alleviate symptoms. He suggested using a vibration chair, which became popular among patients.
- Other methods : Some doctors experimented with combinations of various substances, such as phosphorus, and the application of electric current to the spinal cord and muscles.
Despite the limited effectiveness of these methods, they reflect the doctors’ desire at the time to help patients. Each step brought medicine closer to discovering more effective treatments, such as therapy using levodopa (Fahn, S., 2014).
By the middle of the last century, surgical methods began to be used — such as the destruction of certain areas of the brain to reduce symptoms (Elsworth, J.D., 2020)
In the 1940s and 1950s began using treatments for Parkinson’s disease such as thalamotomy and pallidotomy. These procedures helped reduce tremor and improve movement. They were performed only once and did not require the implantation of any devices into the body. To destroy brain structures, chemicals like alcohol and freezing were used. Among procedures involving the penetration of instruments into the brain, thalamotomy with the use of an electrode and radiofrequency exposure, similar to a microwave at the tip of a needle, is still used today.
These procedures were beneficial because they significantly reduced the motor symptoms of the disease. However, they had their drawbacks. Since they permanently damaged certain parts of the brain, this sometimes led to problems with memory and speech.
Due to these disadvantages, and because new methods such as deep brain stimulation have emerged, thalamotomy and pallidotomy have become less frequently used. Especially with the advent of effective therapy with levodopa medications.
| Period | Approach | Description |
|---|---|---|
| 1940-e – 1950s | Destructive Procedures (Pallidotomy, Thalamotomy) | Surgical destruction of brain areas to reduce motor symptoms |
| 1960-е – 1980s | Reduction in the Number of Surgeries | The introduction of levodopa led to a reduction in surgical interventions. |
| 1990-е – present time | Deep brain stimulation ( DBS) | Reversible change in brain activity using implanted electrodes, electrical stimuli |
| 2010-е – present time | Focused ultrasound MRgFUS, MRgFUS) | Non-invasive treatment by deactivating cells that cause tremor and stiffness through the heating effect of ultrasound waves |
| Future (experimental) | Gene therapy, cell therapy, optogenetics, drug delivery | New approaches aimed at altering the course of the disease |
Methods of treating Parkinson’s have changed since George Cotzias proposed using high doses of levodopa. This discovery radically changed the approach to treating Parkinson’s disease and remains the most effective treatment method for patients with this condition to this day (Fahn, S., 2015).
Levodopa, or L-Levodopa not only helped many people with Parkinson’s disease but also had a significant impact on the entire field of neurology. Before its introduction, effective treatments for Parkinson’s disease were limited
The invention of high doses of levodopa was a revolution in medicine, giving patients with Parkinson’s disease hope for a better life and significantly improving their quality of life
Renaissance of Surgery
Levodopa does not eliminate the cause of the disease, but it has extended the quality of life for patients with Parkinson’s disease. However, the drug’s effect diminished over time for a number of reasons, some of which are removable, and some are not. An increase in medication dosage was required. Particularly large doses caused complications in the form of new involuntary movements, called dyskinesias, rigidity increased, and even high doses gradually stopped working.
Surgery came to the rescue of levodopa!
Deep brain stimulation was first used by a doctor named Alim-Louis Benabid in 1987. He used this technique to reduce tremor in people with Parkinson’s disease. Later, in 1995, another doctor, Pierre Pollak, began using this technique to treat Parkinson’s disease in another part of the brain, and by 1998 the method became clinically applicable.
The technique, called deep brain stimulation, helps reduce excessively synchronized oscillations in parts of the brain associated with movement. It is a method in which electrodes are implanted in the brain to influence abnormal nerve cell activity. This is achieved by delivering a weak electrical current to specific areas of the brain, which can alleviate the symptoms of Parkinson’s disease.
Essentially, this technique helps reduce unnecessary connections in the brain that cause movement problems in people with Parkinson’s disease. It allows for improved control over movements and reduces unpleasant symptoms such as tremor (Li, S. and Le, W., 2017). This method has many advantages. The deep brain stimulator can be adjusted and even turned off, unlike other methods. It provides long-term symptom relief and has less negative impact on cognitive abilities than other surgical methods.
However, deep brain stimulation also has drawbacks. The surgery carries risks such as infection, bleeding, and device malfunctions. The method is expensive and requires regular maintenance: battery replacement and parameter adjustment. Additionally, it does not significantly affect non-motor symptoms, such as cognitive decline or dysautonomia.
Recently Registered Drugs and Treatments
What new drugs for the treatment of Parkinson’s disease have been registered recently?
Vialev/ProDopa (foslevodopa/foscarbidopa) – subcutaneous pump for continuous delivery levodopa and carbidopa, similar to a pump for diabetics Inbrija levodopa – inhaler with fast-acting medication levodopa, allowing for the rapid relief of movement symptoms Nourianz
Krexont (carbidopa and levodopa) – an extended-release medication providing prolonged release
MRI-guided focused ultrasound
Focused ultrasound is a non-invasive method, widely approved worldwide initially for the treatment of tremor, and slightly later for dyskinesias. This method is also used to treat stiffness and rigidity in Parkinson’s disease. More details about the method can be read in our separate article
It would be logical to eliminate the causes of the disease. Therefore, the future of disease treatment lies in the following main directions:
Stop the Death of Brain Cells
1. To do this, it is necessary to develop and deliver drugs to the brain. New drugs could modify the genome or biochemical processes in cells to stop their death
2. Drug delivery is a separate issue related to the presence of a special barrier in the brain that prevents substances from penetrating into the brain. Here, brain implants are being developed, and the barrier is opened using microbubbles exploded by focused ultrasound
Detoxify the body from harmful metabolites and normalize metabolism
Alpha-synuclein accumulation
Many scientists believe that a special protein, alpha-synuclein, plays an important role in the development of Parkinson’s disease. This protein can accumulate in the brain and cause various problems. Therefore, research is being conducted on how to stop its accumulation and spread between brain cells. One approach is to try to reduce the amount of this protein or accelerate its removal from the body.
What trials are new methods undergoing? Scientists find it difficult to conduct trials because there are no animals that manifest the disease in the same way as humans. Therefore, they create models that only remotely resemble the symptoms of Parkinson’s disease in humans. Another difficulty is that scientists do not yet know how to accurately measure the accumulation of this protein in the brain to test the effectiveness of new drugs. However, despite this, scientists are actively working to overcome these problems.
In which directions are the studies moving?
Currently, scientists are exploring five main ways to combat alpha-synuclein. These include (Sardi, S.P., 2018):
- reduction of its production,
- attempt to prevent it from clumping inside cells
- acceleration of its destruction inside
- acceleration of its destruction outside the cells
- reduction of this protein’s entry into brain cells
How can this be done?
1. Set the body’s immunity for cleansing
2. Use external antibodies for cleansing, like “cleansing serum “
For example BIIB054 (Weihofen, 2019) и RO7046015: These antibodies are aimed at preventing the spread of aggregated alpha-synuclein
Phase two trials of new drugs for the treatment of Parkinson’s disease are underway. These drugs are special antibodies that can combat the protein involved in the disease. Two such drugs have already been tested—cinpanemab and prasinezumab. They show results in studies that assess how well they help improve patients’ conditions (Espay, A.J. and Okun, M.S., 2023). A later publication noted that prasinezumab may slow the progression of motor symptoms in patients with Parkinson’s disease in the long term. However, further research is needed to confirm these findings ( NCT03100149, Pagano, G., Monnet, A., Reyes, A. et al., 2024).
Prevention of Protein Aggregation
One of the promising studies considers the use of special molecules called intratabs. These are small parts of protective molecules that can enter cells. They are capable of binding to certain harmful proteins and preventing their accumulation. Such methods work in animal experiments and help reduce the number of harmful proteins, protecting brain cells from damage. Improved versions of such molecules are already in development.
There is also an interesting project from companies Neuropore Therapies и UCB Pharma. They create a special chemical compound called NPT200-11, which prevents harmful proteins from interacting with cells. Initial tests on mice showed good results, but further development is on hold
Finally, in Proclara Bioscience created an unusual hybrid combining two different proteins. This hybrid can bind to harmful proteins and reduce their accumulation. This may protect important cells in the brain. An interesting study using this hybrid is already being tested for safety and to help people with Parkinson’s disease.
Autophagy
One of the methods is related to improving a process called autophagy. Thanks to autophagy, cells can cleanse themselves of unnecessary elements, such as specific proteins that can damage brain cells. Researchers want to find a way to enhance autophagy to reduce the harm from these proteins.
One of the possible drugs for this is MSDC-0160, originally developed for diabetes, which can alter processes within cells, reducing harm. It is being studied as a potential treatment for Parkinson’s disease due to its safety and ability to reach the human brain.
Another interesting method is the use of special inhibitors, commonly used in leukemia treatment. These inhibitors affect protein balance in cells and may help combat brain cell damage. A trial of one such inhibitor was recently conducted, and improvements were observed in some patients, inspiring scientists for further research (Sardi, S.P., Cedarbaum, J.M. and Brundin, P., 2018)
Immunotherapy to reduce the availability of aggregated pathological alpha-synuclein protein
Immunotherapy to Reduce the Availability of Aggregated Pathological Protein – this is an idea in the treatment of Parkinson’s disease that is currently undergoing clinical trials. Immunotherapy can be active (when the immune system is stimulated) and passive (when special antibodies are introduced).
Company Prothena developed a drug called PRX002, which is currently being tested. This drug is a special antibody that fights the harmful parts of the alpha-synuclein protein. Trials on healthy individuals have shown that it is safe and well-tolerated, especially in high doses.
When people in the trials took this drug, the amount “free ” alpha-synuclein in their body decreased, especially with a high dose. This effect lasted from two to four weeks after a single dose. Research shows that the drug may reduce the accumulation of the harmful protein associated with brain function deterioration.
What about real patients? The study of this drug in people with newly diagnosed Parkinson’s disease began in June 2017. This was done in collaboration with the company Roche. All this is being done to find out if the medication can truly help Parkinson’s patients. It is still unknown how effective it will be in improving the condition of people with this disease (Sardi, S.P., Cedarbaum, J.M. and Brundin, P., 2018). Mutations in the GBA gene are associated with Gaucher’s disease and may also increase the risk of developing Parkinson’s disease ( PD). Gene GBA is responsible for converting one substance into another in cells. If it works poorly, it can lead to diseases. Many people with Parkinson’s disease have mutations in this gene, but not everyone is aware of it
In Parkinson’s disease associated with this gene, people may become ill faster and have more problems, such as with memory. People with mutations in GBA may start suffering from memory loss faster than those who do not have them. This is important to know because sometimes they develop dementia (memory loss and other cognitive issues).
To accurately determine if a person has mutations in the gene GBA, it is necessary to conduct gene analysis. However, not everyone with mutations will develop Parkinson’s disease, so it cannot be predicted with certainty. Currently, this knowledge does not aid in treatment, but in the future, when treatment becomes more personalized, this may change.
Paradigm Shift: Is Alpha-Synuclein to Blame?
Scientists long believed that Parkinson’s disease occurs because a harmful protein begins to accumulate and form harmful clumps that interfere with brain function. This approach was called “Proteinopathy “ — that is, the problem is due to the improper behavior of the protein. But now scientists are starting to look at it differently. They think that the accumulation of this protein is not the cause of the disease, but rather the body’s reaction to other problems. For example, it may be an attempt to protect brain cells from harmful effects. The new approach is called “protein deficiency “ — the idea that Parkinson’s disease is related not to an excess of harmful protein, but to a deficiency of something else, such as a cleansing protein (Espay, A.J. and Okun, M.S., 2023). When the protein turns into clumps (called amyloids or Lewy pathology), it loses its beneficial functions. Scientists believe that the disease does not start with the appearance of these clumps but with the disappearance of the normal protein. It’s as if the brain lost an important tool for functioning, and the cells began to suffer. The new approach suggests that instead of trying to remove harmful clumps, the focus should be on restoring the normal protein. It’s like restoring a forest by planting new trees rather than removing stumps. Scientists believe that restoring the normal protein may help the brain function better, even if the disease has already begun.
Restore or replace dead cells
This can be done in at least two ways
1. Regeneration. Encourage neighboring cells to divide and specialize (differentiate) in the functions of lost cells. We constantly see this process when we get injured and watch the wound heal. In the brain, one reason this doesn’t happen is that cell division and growth would disrupt connections between neurons, leading to a loss of learning. Therefore, there are mechanisms of regeneration in the brain, but they are not as “alive ” for example, on the skin
2. Grow and transplant cells from outside
To prosthetically replace the function of dead cells
Why not create a chip, like Neurolink, that would replace the function of dead neurons?
Improve existing treatment methods
1. Create artificial intelligence in a neurostimulator that will modify the stimulation mode.
2. Find more precise and effective application points for surgical treatment with focused ultrasound, radiofrequency ablation, or deep brain stimulation.
Scientists are working on new treatment methods that could change the approach to combating Parkinson’s disease. Here are the main directions:
- Gene Therapy and RNA-Based Methods for Parkinson’s Disease — help correct errors in cells
- Stem Cells and Repair of Damaged Tissues — for replacing dead brain cells in patients with Parkinson’s
- New Methods of Drug Delivery to the Brain — so that medications can pass the barrier separating the blood from brain cells and act more precisely on the causes of Parkinson’s disease
- Modern Brain Surgeries — enhanced technologies, such as new devices for deep brain stimulation and ultrasound
- Immunotherapy and Protection of Brain Cells Dying in Parkinson’s Disease — to slow down the destruction of neurons
- Artificial Intelligence and Brain-Machine Technologies — to create intelligent systems that help manage disease and replace lost functions
Each of these areas offers hope for more effective treatment in the future!
Transplantation of dopaminergic stem cells to a patient
Scientists and doctors have long worked on figuring out how to transplant stem cells to treat Parkinson’s disease. The first experiments with cell transplantation began on animals, using embryonic brain cells to replace damaged neurons. These studies showed that such cells could survive and help restore lost functions. Later, scientists began working with stem cells that can be transformed into the necessary brain cells to use them for treating people.
Recently, surgeons (Z. Chen, 2023) transplanted stem cells into a human for the first time, using cells created from the patient’s own blood. These cells were specially processed in the laboratory to become neurons that produce dopamine — a substance necessary for normal brain function. The operation was successful, and after two years of observation, the patient had no serious side effects, and their condition stabilized. This method promises to be safer because the cells are taken from the patient themselves, and the body does not reject them.
In the future, scientists plan to conduct more similar operations to understand how long the effect lasts and whether results can be improved. Researchers are currently working on making the cell creation process even more precise and faster, as well as studying how to apply this method to a larger number of patients. This is just the beginning, but it is already clear that stem cells could become an important step in treating brain diseases.
Source: Chen, Z. and Zhao, G., 2023. First-in-human transplantation of autologous induced neural stem cell-derived dopaminergic precursors to treat Parkinson’s disease. Science Bulletin, 68(22), pp.2700-2703. https://www.sciencedirect.com/science/article/pii/S209592732300720X
Genetic therapy
Gene therapy for the treatment of Parkinson’s disease is based on the use of genetic methods to alleviate symptoms with fewer side effects compared to traditional methods. The therapy uses three approaches: silencing, replacement, or repair of the damaged gene. This can lead to a significant reduction in symptoms, providing improved quality of life for patients with Parkinson’s disease.
Gene therapy is focused on two target groups:
1. Modifying treatment is aimed at stopping neuron degeneration and allows for the stimulation of neuron regeneration. Growth factors that protect neurons play an important role. Thus, genetic therapy opens up great prospects in the fight against this disease
2.Non-modifying — for the construction of enzymes that help produce dopamine. Currently, clinical trials are underway for new drugs such as Prosavin (Dumbhare, O. and Gaurkar, S.S., 2023)
How does gene therapy work?
Gene therapy uses several approaches:
1. Introduction of neurotrophic factors (for example, GDNF):
- Neurotrophic factors are substances that help brain cells survive and function. For example, GDNF (glial cell line-derived neurotrophic factor) supports dopamine neurons, preventing their death
- Using gene therapy, scientists can deliver a gene that produces GDNF, directly into the patient’s brain. This helps improve cell function and reduce disease symptoms.
2. Optogenetics and Chemogenetics:
- These methods allow precise control of neuron activity. For example, scientists can use light-sensitive proteins to “include ” or “turn off ” certain brain cells, affecting their function
- It helps to correct disruptions in brain circuits that cause motor symptoms such as tremor or stiffness.
3. Using Viruses for Gene Delivery
- Scientists use safe viruses (for example, AAV-vectors) to deliver the necessary genes into brain cells. These viruses work like “Couriers “, transferring genes to the desired location
- This method provides a long-lasting effect as the genes start working inside the cells, producing beneficial substances.
4. Non-viral methods:
- There are other methods of gene delivery, such as using nanoparticles or liposomes. These methods are simpler, but their effect is usually less long-lasting, requiring repeated administration.
What difficulties exist?
Despite the prospects, gene therapy faces a number of challenges:
- Long-term Safety:
- Scientists need to understand how long the treatment effect lasts and what side effects may occur years after therapy.
- Delivery methods:
- Gene delivery through the blood-brain barrier (the brain’s natural protective layer) is a complex challenge. Scientists are working on improving technologies to make this process safe and effective.
- Effectiveness:
- Not all patients respond to treatment the same way, so methods need to be developed that suit different people.
Gene Therapy Opportunities:
Gene therapy can:
- Protect brain cells from destruction
- Restore the function of damaged cells
- Reduce symptoms of the disease, such as tremor and stiffness.
- Minimize the side effects that occur with the use of standard medications.
It is important to note that gene therapy is still in the clinical trial stage. Scientists are testing it on small groups of patients to ensure its safety and effectiveness.
Future Prospects
Gene therapy opens new possibilities for treating Parkinson’s disease:
- Disease Progression Halt:
- If it is possible to protect brain cells from destruction, the disease may stop progressing.
- Early Intervention:
- In the future, gene therapy may be used at the early stages of a disease, before serious symptoms appear.
- Combined Approaches:
- Gene therapy can be used alongside other treatments, such as medication or deep brain stimulation.
Let’s hope that in the coming years, gene therapy will become available to a wide group of patients and help improve their quality of life (Saravanan, C.R., Eisa, 2024)
| Gene Therapy Approaches | Mechanism and Action | Goals |
|---|---|---|
| Neurotrophic | • neuron survival • functioning | • Glial cell line-derived neurotrophic factor GDNF) • Brain-Derived Neurotrophic Factor ( BDNF) • Neurutin NRTN) |
| Alpha-synuclein | • reduction of aggregation • decrease in alpha-synuclein expression | • Alpha-synuclein gene ( SNCA) |
| Gene Editing CRISPR-Cas9) | • correction of specific genetic mutations | • Kinase 2 with a leucine-rich repeat ( LRRK2) • Alpha-synuclein SNCA) • Parkin PARK2) • Kinase 1, induced PTEN (PINK1) |
| Neuromodulation | • changes in neural circuit activity • elimination of movement disorders | • Basal ganglia-thalamo-cortical circuits |
| Based on stem cells | • restoration of lost • dopamine neurons | • Pluripotent stem cells ( iPSCs) • Embryonic stem cells ESCs) • Neural stem cells ( NSCs) |
Drug Delivery Across the Blood-Brain Barrier
Focused ultrasound FUS)
Focused ultrasound FUS) can be used for the temporary opening of the blood-brain barrier. Microbubbles are injected into the vein, which cavitate under the influence of ultrasound and open microholes in the barrier for several hours. After such a procedure, the permeability of the barrier temporarily allows for drug delivery. We have a separate article on improving drug delivery with ultrasound
Published attempts on mice for stem cell delivery (Wu, S.K., Tsai, C.L., Mir, A. and Hynynen, K., 2025)
Drug Delivery Using Nanoparticles
Scientists are currently developing nanomaterials (liposomes, polymer nanoparticles) for targeted drug delivery to the brain.
Exosomes as a Drug Delivery System
Exosomes are extracellular vesicles ranging from 30 to 150 nm in size, involved in intercellular communication and biomolecule transport.
Exosomes have a natural ability to cross the blood-brain barrier. They can be modified for targeted drug delivery. They are stable in biological fluids and can be derived from various cells, such as microglia and astrocytes, enhancing their flexibility as transport vehicles.
What are exosomes made of?
Exosomes have a bilayer phospholipid membrane containing lipids, proteins, and genetic elements (microRNA, mRNA, DNA). They contain specific exosomal proteins:
- Heat shock proteins ( HSP70, HSP90), involved in antigen presentation
- Tetraspanins that provide structural stability to exosomes
- Proteins ALIX и TSG101, important for the formation of exosomes through the endosomal sorting complex ( ESCRT).
How are exosomes formed?
The process of exosome formation is complex:
- Early endosomes are formed by invagination of the plasma membrane.
- Early endosomes mature into late endosomes (multivesicular bodies MVBs), where does the sorting of proteins and lipids occur
- Internal vesicles ILVs) are released from the endosome, forming exosomes
How do scientists plan to use exosomes in the treatment of Parkinson’s disease?
- Exosomes can carry drugs, biomolecules, and therapeutic compounds that have a positive effect on brain cells.
- Research shows that exosomes derived from stem cells can be used to treat neurodegenerative diseases by repairing damaged cells.
- Exosomes derived from diseased cells can also spread pathology, necessitating careful control of their source.
Overcoming the Blood-Brain Barrier with Exosomes:
- Exosomes have a unique ability to pass through the BBB due to their small size and biological properties.
- Engineering approaches allow for the modification of exosomes for targeted drug delivery, minimizing side effects
This is a promising tool for drug delivery in neurodegenerative diseases. They can overcome barriers that limit the effectiveness of traditional treatments and provide targeted impact on damaged brain cells. However, research is needed, including safety and efficacy assessments and the development of production methods (Rai, S., 2025 ).
Enhancing Deep Brain Stimulation: Adaptive DBS
Adaptive Deep Brain Stimulation ( aDBS) — this is a new technology developed to help people with Parkinson’s disease. The device uses sensors in the brain to detect abnormal activity that causes issues like “freezing of gait” FoG), when a person suddenly cannot move. When the device detects this abnormal activity, it adjusts the stimulation in real-time to prevent or reduce such episodes. Unlike older systems that operate continuously aDBS activates only when necessary, making it more efficient and reducing side effects. Scientists continue to improve the technology, finding more precise brain signals to track and creating smart algorithms that predict and prevent FoG before it begins (Philipp Klocke, 2025)
Repetitive transcranial magnetic stimulation ( rTMS)
Repetitive Transcranial Magnetic Stimulation ( rTMS) is considered a promising non-invasive method for treating motor and non-motor symptoms of Parkinson’s disease (PD) in improving cognitive function, depressive symptoms, and walking ability in patients with Parkinson’s disease (PD)
What is rTMS?
- rTMS — this is a form of non-invasive brain stimulation, where the magnetic field created by a coil penetrates through the scalp and skull, altering the excitability of the cerebral cortex
- Effects depend on the frequency of stimulation:
- High frequency (≥5 Hz) causes cortical excitation.
- Low frequency (≤1 Hz) has an inhibitory effect.
- rTMS can affect various areas of the brain:
- Primary Motor Cortex M1) — for the treatment of motor symptoms
- Dorsolateral prefrontal cortex ( DLPFC) — for the treatment of depression.
- Supplementary Motor Area ( SMA) and the cerebellum — to improve gait.
Recent meta-analysis of 15 randomized controlled trials ( RCTs) showed (Wang M, Zhang W, Zang W, 2024):
- Cognitive function: rTMS significantly improved test results MOCA (MD = 2.98, 95% CI 2.08–3.88, P = 0.000).
- Depression: Reduction of depressive symptoms on the scale HAMD (SMD = -0.43, 95% CI -0.72–-0.13, P = 0.004).
- Ability to Walk: Performance Improvement:
- TUGT (SMD = -0.72, 95% CI -1.43–0.00, P = 0.048).
- FOG-Q (SMD = -0.54, 95% CI -0.97–-0.11, P = 0.01).
- UPDRS-III (SMD = -0.66, 95% CI -0.84–-0.47, P = 0.000).
The authors consider the effects of treatment rTMS include:
- Improvement of motor symptoms, such as gait and “freezing of gait “.
- Reduction of depressive symptoms, which positively affects mood and overall mental health
- Improvement of cognitive functions, including working memory and executive functions.
However, the study has its limitations:
- Significant variability in treatment parameters (frequency, stimulation site, duration), which complicates the comparison of results
- Incomplete understanding of cognitive effects rTMS.
- Variability of Results in Gait Improvement
Repetitive transcranial magnetic stimulation ( rTMS) demonstrates significant potential in improving cognitive function, depressive symptoms, and walking ability in patients with Parkinson’s disease rTMS may be an effective additional method for treating motor and non-motor symptoms of Parkinson’s disease in the future, further research is needed
Transcranial Direct Current Stimulation tDCS)
In the 2024 meta-analysis, the authors note that the application tDCS (transcranial direct current stimulation) on the dorsolateral prefrontal cortex ( DLPFC) effectively improved motor and cognitive functions (Lee, H., Choi, B.J. & Kang, N., 2024).
Another meta-analysis showed that the effect of transcranial direct current stimulation tDCS) in patients with Parkinson’s disease (PD) does not differ significantly from the placebo effect (Duan Z, Zhang C., 2024).
The analysis identified three possible types of impact tDCS:
- Slight positive effect (effect size 0.32) in patients with mild motor symptoms ( UPDRS-III = 13).
- Lack of effect in patients with moderate symptoms ( UPDRS-III = 22–25).
- Minor adverse effect (effect size -0.48) in patients with severe symptoms ( UPDRS-III = 40).
Age also affects the results: effect tDCS close to zero in patients aged 64, while the duration of the disease, its stage, and the number of stimulation sessions do not explain the differences in results.
Research Issues and Limitations:
- Variability of results: Effects tDCS on motor and cognitive functions vary greatly between studies, which is related to stimulation parameters, patient characteristics, and methodology
- Incomplete Personalization: Parameters tDCS usually fixed and not adapted for each patient, unlike deep brain stimulation ( DBS), which is individualized
- Technological limitations: tDCS has low spatial resolution, leading to the activation of brain areas outside the target zone. Additionally, the effect may be due to nonspecific mechanisms such as placebo, changes in task execution strategy, or peripheral effects.
- Cognitive functions: Modulating cognitive impairments remains a complex task, as they are associated with the degeneration of multiple neurotransmitter systems (dopaminergic, cholinergic, noradrenergic) and their interactions.
Comparison tDCS и DBS:
- DBS: Deep brain stimulation is a surgical method that provides consistent electrical stimulation and individual parameter adjustment, making it more precise and effective for treating severe motor symptoms.
- tDCS: Direct changes in the brain from tDCS remain in question, and its effects may be temporary and nonspecific.
Recommendations for Future Research:
- Personalization of Approach: Consider individual differences, such as genetic background (e.g., polymorphisms LRRK2, PARK2, SNCA and others) and comorbidities
- International Multicenter Studies: Conducting large studies with subgroup analysis based on patient characteristics
- Alternative Methods: Research of new technologies, such as transcranial interference stimulation, to enhance the accuracy and effectiveness of therapy.
In conclusion it can be said that at the moment there is insufficient evidence of clinically significant effects tDCS on motor and cognitive functions in patients with Parkinson’s disease. The high variability of results and the limited scope of research require further development and improvement of technologies to create personalized and effective treatment methods.
Neuroprosthesis helping to walk with Parkinson’s disease installed in a person
Development of a Neuroprosthesis
Researchers have created an innovative neuroprosthesis designed to help people with Parkinson’s disease regain the ability to walk (Milekovic, T., Moraud, E.M., Macellari, N. et al., 2023). The device works by stimulating specific areas of the spinal cord that control leg movements, mimicking natural walking patterns. Initially, the neuroprosthesis was tested on non-human primates that exhibited similar walking difficulties as those seen in people with Parkinson’s disease. The results were promising: significant improvements were observed in walking skills, balance, and overall mobility.
Surgical Implantation and Trials
After successful trials on primates, the neuroprosthesis was implanted in a 62-year-old man with late-stage Parkinson’s disease who suffered from severe mobility issues. The device was carefully adapted to his spinal anatomy and connected to an implantable pulse generator. During the trials, the neuroprosthesis was found to be compatible with existing treatments such as deep brain stimulation, enhancing the effect of both therapies. The patient began taking longer steps, his balance improved, and the number of episodes “Freezing ” decreased while walking
Impact on Quality of Life
The implementation of this neuroprosthesis represents a significant step forward for people with Parkinson’s disease. The device not only restored some natural movements but also significantly improved the patient’s quality of life. After several months of rehabilitation with device support, he reported a reduction in falls and an increased ability to independently engage in daily activities. This breakthrough offers hope to many others facing similar challenges, demonstrating the potential of modern technologies in transforming lives.