No Cure for Parkinson’s! Why?

What is Parkinson's Disease?

Parkinson's disease is a progressive movement disorder of the nervous system. It causes neurons in certain parts of the brain to weaker, become damaged, die leading to symptoms which include problem swath movement, tremors, stiffness and impaired balance. A symptom stress people with PD may have difficulty walking asking or competing other simple tasks.

Parkinson's and the brain

Most common symptoms results from the loss of neurons in the area near the base of the brain called Substantia Nigra. The neurons here produce dopamine, which signals the brain to produce smooth, purposeful movement. Studies show that people with PD have lost 60% to 80% or more of the dopamine producing cells in the substantia nigra but the time symptoms appear.

Brain with Parkinson’s Disease left and Brain without Parkinson’s Disease Right: Substantia Nigra Degeneration in PD and Lewy Bodies

Moreover, the nerving which produce neurotransmitter norepinephrine, which controls voluntary functions. This loss explains the fact that several patients symptoms are not related to movement instead to fatigue and blood pressure changes.

The affected brain cells of people with PD contain Lewy bodies which are deposits of protein alpha-synuclein.

Epidemiology:

PD affects an estimated 10 million people globally. It is the 2nd most common neurodegenerative discover after Alzheimer’s. Most people are diagnosed after 60 years of age though before age of 50 is accounted for 5–10% of cases. The number of Parkinson's cases is rising worldwide due to aging populations, improved diagnosis and increase awareness. Cases of incidence is roughly 13–20 new cases per 100000 people per year, globally.

Risk Factors:

1. Genetics: Causes approximately 10% of PD cases and are more common with patients with earlier PD (before age of 50).

Mutation in genes:

1. Dominant inheritance :SNCA ( causes accumulation of Lewy bodies) and LRRK2 (most common genetic cause)

2.Recessive inheritance: DJ1( Protects cell from oxidative stress → mutation → increases vulnerability) and PINK1(Causes early onset of Parkinson’s, often before the age of 40)

1. Environmental factors: Exposure to chemicals like paraquat and long term exposure to manganese, lead and other metals contribute to PD. Certain solvents and industrial pollutant may affects neuronal health. It’s a major concern for people living in rural areas, working in mines or those who have long term exposure to air pollution.
2. Head Trauma: Repeated blows to the head. However this is a very rase case and hence uncertain is frequency of head trauma increase your risk.

Symptoms of Parkinson Disease:

PD has different effects and rate of progression in different individuals. It typically begins one side of the body and then eventually effects not sides. Most common symptoms are:

1. Tremor: Shaking begins in the hand. At times it starts with foot or jaw. It is a rhythmic back and forth motion which causes a person to rub their thumb and forefinger to the which may appear as ‘pill rolling’. Most obvious when tremor occurs when hand is at rest or person is under stress. Commonly occurs during sleep and may improve is the person makes intended and purposeful movement.
2. Rigidity: Muscle stiffness or resistance to movement. Usually results in ‘cogwheel’ rigidity which is short jerky movement when another person tried to move the individuals arm.
3. Declining posture: Imbalance and changes in posture which increases risk of fall. Prolonged decline in posture leads to ‘parkinsonian gait’. A tendency to learn forward, reduced swinging of arms, festination and start hesitation.
4. Bradykinesia: Slowing down of spontaneous movement. Makes doing simple task more default and leads to masked face, a condition in which the personas face is less expressive.

MRI of the brain in a somnolent patient with bradykinesia and rigidity

Other symptoms:

1. Mental and emotional health problems
2. Difficulty swallowing and chewing
3. Speech changes
4. Pain and fatigue
5. Muscle cramps

How is Parkinson Disease diagnosed?

I) Diagnosis:

1. Physical and neurological exam: this includes taking medical history and take a neurological exam.
2. Blood and Lab test along with imaging tests like MRI and brain ultrasound and PET scan: Rules out other conditions that may cause the symptoms.
3. Dopamine Transporter scan (DAT): Not necessary but support the suspicion of PD by identifying different types of tremors.

II)Treatment:

Since there is no cure, medicine are provide to reduce pain through either producing dopamine or controlling the secondary effects of PD.

1. Levodopa: Effects PD medicine. It is a natural chemical that passes into brain and become dopamine hence increase dopamine levels.
2. Inhaled Levodopa: Helps to managing symptoms when oral medicine stop working.
3. Amantadine: Short term relief of mild , early stage PD symptoms. Controls involuntary movements.
4. Pimavanserin: Treats hallucination and deduction that can cocksure during Arkin’s disease.

Mechanisms of peripheral levodopa resistance in Parkinson’s disease

Why Current Treatments Sometimes Fail

Despite these therapies, many patients experience limited or inconsistent benefits over time. Factors contributing to treatment failure include:

1. Progressive neuron loss: As PD advances, medications may become less effective.
2. Side effects and complications: Long-term use of levodopa can cause involuntary movements (dyskinesia) and fluctuations in motor control.
3. Individual variability: Genetic and environmental factors influence how patients respond to treatments.
4. Incomplete understanding of disease mechanisms: Many non-motor symptoms are poorly managed because current therapies mainly target dopamine.

Here’s whats happening

Parkinson’s disease is marked by the death of dopamine-producing neurons in the brain everyone is trying to find ways to replicate the process of dopamine producing. However, is dopamine the actual problem, Is this the cure?

WRONG!!!

Why?Because right now all the solutions bring brought about are simply trying to relive the symptoms and not find a real solution. Dopamine is not of only 1 type but of 10 different kinds. Each gets effected differently in the patient with the disease. Trying to simply produce dopamine does not solve this problem, instead it masks the actual issue tailgating the idea as though dopamine production is the solution.

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To cure Parkinson's we need to find a way the creates this problem of disappearing neurons.

So the question is not how but WHY are the neurons dying in the first place? and this is the question I aim to solve.

Ongoing Efforts to Solve These Challenges

Researchers are exploring multiple strategies to overcome treatment limitations:

1. Gene and cell therapies: Targeting underlying genetic causes or replacing lost dopamine-producing neurons.
2. Personalized medicine: Tailoring treatments based on patient genetics, symptom profile, and disease progression.
3. Neuroprotective strategies: Developing drugs to slow neuron degeneration before symptoms worsen.
4. Advanced drug delivery systems: Methods like continuous infusion or inhaled formulations to stabilize medication effects.
5. Hands-on research: Gaining clinical and laboratory experience helps understand why treatments fail and contributes to the development of better therapies.

About the author:

I am Agam Kaur Kohli, a high school student passionate about biomedical research, with a focus on personalized medicine for Parkinson’s Disease. I am exploring the intersection of neuroscience, translational research, and clinical applications. Through projects like NEURONEX, I aim to understand Parkinson’s disease mechanisms, investigate why current treatments fail, and contribute to developing a cure, combining academic research with hands-on experience in lab and clinical settings.