Parkinson’s disease research has advanced significantly over the past two centuries. After Parkinson’s disease was recognized as a distinct neurological condition in the early 1800s, researchers began working to better understand it and develop treatments, including medications and surgical procedures.

Below, we’ll explore the history of Parkinson’s disease and highlight important milestones in research, diagnosis, and treatment.

Initial Description of Parkinson’s Disease and Early Developments

British physician James Parkinson was the first person to medically describe Parkinson’s disease as a neurological condition in 1817. In his descriptive study, Parkinson wrote about six people he had observed. He described features of the condition, including tremors and changes in gait and posture, as well as how symptoms progressed over time.

Parkinson also mentioned nonmotor symptoms, including:

About 50 years later, French neurologist Jean-Martin Charcot expanded on the work of Parkinson and named the condition after him. Over the next few decades, several physicians contributed to Parkinson’s research, including British neurologist William Gowers. In the 1880s, Gowers studied Parkinson’s disease characteristics, including joint deformities, based on observations of 80 people he treated.

As the 1900s approached, scientists at a French neurological school developed drawings depicting the disease’s progression. Between the 1920s and 1960s, researchers increasingly linked Parkinson’s disease to changes in specific areas of the brain, particularly the substantia nigra in the midbrain.

Milestones in Parkinson’s Disease Research and Treatment

The sections below list major milestones in Parkinson’s disease research and treatment in chronological order.

During the early years of Parkinson’s disease treatment, medications derived from the belladonna plant were used to treat symptoms. By blocking the action of the brain chemical acetylcholine, these anticholinergic treatments helped reduce tremors.

In the 1940s, synthetic anticholinergic drugs such as trihexyphenidyl were introduced and marketed for Parkinson’s. These drugs, which reduce activity of the neurotransmitter acetylcholine, were used for symptoms such as tremors and rigidity (muscle stiffness).

In the early 1960s, scientists became interested in the role of the neurotransmitter dopamine and the use of levodopa (L-dopa) to treat Parkinson’s disease. Levodopa can help with movement-related symptoms and may reduce or eliminate tremors.

However, early treatment with levodopa caused troublesome gastrointestinal side effects. Greek physician George Cotzias found that gradually increasing dosage could improve a person’s tolerance to the drug.

Amantadine was originally developed in the 1960s as an antiviral drug for the flu. It was later found to be useful in treating Parkinson’s disease.

Amantadine (Gocovri, Osmolex ER) affects dopamine and other brain chemicals and may help with symptoms such as tremors, uncontrolled movements, and stiffness. It’s frequently used alongside other Parkinson’s medications, such as anticholinergics or carbidopa-levodopa, and may reduce dyskinesia (involuntary movements) caused by levodopa.

In the late 1960s, researchers found that pairing levodopa with dopamine decarboxylase (DDC) inhibitors increased the amount of levodopa available to reach the brain. They also found that this combination reduced side effects such as gastrointestinal problems and allowed lower doses of levodopa to be used.

In 1975, carbidopa-levodopa became commercially available in the U.S. Levodopa has also been combined with another DDC inhibitor, benserazide.

Dopamine agonists were studied from the 1950s into the 1970s and became available for Parkinson’s treatment in 1978. Dopamine agonists bind to dopamine receptors and act like dopamine in the brain. Unlike levodopa, they don’t need to be converted into dopamine.

Early dopamine agonists included drugs derived from ergot (a type of fungus):

Many older ergot-derived dopamine agonists are now rarely used because of the risk of certain heart and lung problems.

Monoamine oxidase B (MAO-B) inhibitors slow the breakdown of dopamine and allow more dopamine to remain available in the brain.

Research into MAO-B inhibitors ramped up in the 1960s. The MAO-B inhibitor selegiline was first approved for the treatment of Parkinson’s disease in Hungary in 1977, followed by the UK and the U.S. in the 1980s. Additional MAO-B medications were approved for use in Europe and the U.S. in the 2000s and 2010s.

In the late 1980s, researchers showed that sustained-release carbidopa-levodopa could reduce “off” time (when medication effects wear off between doses).

In the early 1990s, researchers showed that non-ergot dopamine agonists were also effective in treating Parkinson’s disease. Pramipexole and ropinirole were approved for use in the U.S. in 1997.

Catechol-O-methyltransferase (COMT) inhibitors block an enzyme involved in breaking down dopamine. Consequently, they preserve higher levels of dopamine in the brain. These medications are typically used alongside levodopa-based medications to prolong their effect.

COMT inhibitor medications became commercially available in the late 1990s, with newer versions released in the 2000s and 2010s.

Although neurosurgery (brain surgery) has long been considered as a potential treatment for Parkinson’s disease, breakthroughs in treatment with levodopa reduced the use of surgery in the late 1960s. Researchers had also observed that high-frequency electrical stimulation of certain brain areas produced effects similar to those of lesion surgery.

Over the next few decades, research led to a better understanding of the brain circuits involved in Parkinson’s disease, while medical device technology advanced quickly. These developments ultimately led to deep brain stimulation (DBS).

DBS involves implanting a thin wire that delivers electrical stimulation to specific areas of the brain involved in movement. A battery-powered device is typically implanted under the collarbone. These electrical signals help change the irregular brain activity associated with movement symptoms in Parkinson’s.

The U.S. Food and Drug Administration (FDA) approved the use of DBS in stages:

Since the introduction of carbidopa-levodopa, drug development has focused in part on improving the availability of levodopa in the body. Developments in formulations and delivery methods include these FDA approvals:

Where Do We Go From Here?

Although there’s no cure for Parkinson’s disease, research continues to advance. Researchers are working on ways to diagnose Parkinson’s earlier, improve quality of life, and expand treatment options beyond medication, such as DBS. Promising areas of research and development include:

• Cell therapy — Researchers are developing cell therapies that aim to replace dopamine-producing brain cells that are lost in Parkinson’s disease.
• Disease-modifying treatments — Research continues on treatments that could slow or stop Parkinson’s progression. One treatment now in phase 3 clinical trials targets alpha-synuclein, a protein that can build up in the brains of people with Parkinson’s disease.
• Next-generation medications — Several medications are being studied or developed. These include next-generation dopamine agonists and medications to address involuntary movements associated with levodopa treatment.

The future of Parkinson’s disease treatment aims not only to help people manage symptoms today but also develop treatments that could slow disease progression or replace cells lost to the disease.