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.
There are also quite “ancient ” treatment methods that were previously prescribed for many other diseases
Since ancient times, people have used treatments that are still used today for Parkinson’s disease:
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:
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
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.
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
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:
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
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):
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).
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.
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 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.
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.
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
Why not create a chip, like Neurolink, that would replace the function of dead neurons?
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:
Each of these areas offers hope for more effective treatment in the future!
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
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)
Gene therapy uses several approaches:
Despite the prospects, gene therapy faces a number of challenges:
Gene therapy can:
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.
Gene therapy opens new possibilities for treating Parkinson’s disease:
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) |
Saravanan, C.R., Eisa, R.F.H., Gaviria, E., Algubari, A., Chandrasekar, K.K., Inban, P., Prajjwal, P., Bamba, H., Singh, G., Marsool, M.D.M. and Gadam, S., 2024. The efficacy and safety of gene therapy approaches in Parkinson’s disease: A systematic review. Disease-a-Month, p.101754.
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)
Scientists are currently developing nanomaterials (liposomes, polymer nanoparticles) for targeted drug delivery to the brain.
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:
How are exosomes formed?
The process of exosome formation is complex:
How do scientists plan to use exosomes in the treatment of Parkinson’s disease?
Overcoming the Blood-Brain Barrier with Exosomes:
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 ).
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) 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?
Recent meta-analysis of 15 randomized controlled trials ( RCTs) showed (Wang M, Zhang W, Zang W, 2024):
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
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:
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:
Comparison tDCS и DBS:
Recommendations for Future Research:
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.
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.
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
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.
Li, S. and Le, W., 2017. Milestones of Parkinson’s disease research: 200 years of history and beyond. Neuroscience bulletin, 33, pp.598-602.