Parkinson's Disease - A Journey Through History and Treatment

Thank you again, Mr Green, for this great find of this webinar and the suggestion to share its insights. The March 2026 meeting of the Palo Alto Support Group featured a compelling presentation by Dr Shoeb Lallani, a neurology resident at Stanford Neurology, who provided a detailed journey through the history and treatment of the Parkinson's condition. The formal history of the condition began in 1817 when James Parkinson published An Essay on the Shaking Palsy. He was the first to describe the core motor deficits we still look for today, including tremor, rigidity, slowness of movement, shuffling gait, and blood pressure drops upon standing. In the 1860s, Jean-Martin Charcot further distinguished the condition from other movement disorders and coined the term Parkinson’s condition in honour of James Parkinson. Later, in 1912, pathologist Friedrich Lewy discovered protein deposits in the brain now known as Lewy bodies. These are understood to be accumulations of alpha-synuclein protein that lead to neuron death. It was not until the 1950s that Arvid Carlsson discovered that dopamine plays a pivotal role in movement and that its levels are significantly decreased in people with the condition. The 1960s saw the creation of Levodopa, the first drug used to replace missing dopamine. While highly effective in the brain, it caused severe gastrointestinal issues when processed in the stomach. To combat this, chemists developed Carbidopa, which prevents Levodopa from binding in the stomach and reduces nausea. The combination, known as Sinemet, was FDA-approved in 1970 and remains a cornerstone of treatment. Other oral medications have since joined the repertoire, such as dopamine agonists like Pramipexole and Ropinirole which mimic dopamine, and Amantadine, which induces more dopamine release and helps reduce involuntary movements. Additionally, inhibitors like Entacapone and Rasagiline prevent the breakdown of dopamine to allow it to act longer in the system. In the last 25 years, innovation has focused on non-oral delivery to reduce gastrointestinal side effects and motor fluctuations. The Rotigotine patch provides 24 hours of continuous dopamine infusion through the skin, while intestinal gel pumps deliver medication directly into the small intestine. For emergency rescue during severe periods where medication has worn off, a nasal spray of Apomorphine can act within one to two minutes. Surgical history actually predates modern medication. In the 1940s and 1950s, surgeons performed thalamotomies and pallidotomies to target tremors and rigidity. While effective, these irreversible procedures often carried significant side effects for speech and cognition. The 1980s brought the revolutionary Deep Brain Stimulation, which involves placing electrodes into specific brain areas connected to a battery in the chest. It works continuously to override abnormal brain signals and provide symptom relief. Looking toward the horizon, Dr Lallani highlighted several groundbreaking advancements currently in development. Adaptive DBS technology records brain signals and only provides stimulation when it detects an abnormal pattern, which saves battery life and reduces side effects. Stem cell therapy trials in Japan involve taking a person's own skin cells and developing them into dopamine-producing cells to be injected back into the brain. Furthermore, researchers are investigating gene therapies using CRISPR technology to edit out genes that cause familial versions of the condition or to block the production of alpha-synuclein protein entirely. During the discussion, Dr Lallani addressed several practical concerns including dizziness, which can be a symptom of the condition or a side effect of medication. He also noted that freezing of gait remains one of the most challenging symptoms to treat, as standard medications and surgery are often ineffective for it. Most importantly, he emphasised that physical exercise is currently the only known therapy that can truly slow the progression of the condition. While current therapies often act as a temporary fix for symptoms, there is great optimism that the next few decades of research will move us closer to preventing and potentially curing the condition entirely.