Research is actively underway to develop new medications that can slow or stop Parkinson’s disease (PD) progression, while also working to improve the lives of people living with PD today. Learn how lifestyle choices and medication therapy can help you manage Parkinson’s symptoms and what is in the pipeline for 2023.
This article is based on Parkinson’s & Medications - What's New, a Parkinson’s Foundation Expert Briefing webinar presented by Tanya Simuni, MD, Northwestern University Feinberg School of Medicine, Director Parkinson’s Disease and Movement Disorders Center, a Parkinson’s Foundation Center of Excellence.
Moving Science Forward
Globally, Parkinson's is the most rapidly increasing neurological disease and is currently the second most common neurodegenerative disease after Alzheimer's. Researchers are prioritizing science to help them understand the biology behind Parkinson’s disease.
Genetic research is one area that shows promise to push the science forward. However, research seeking to better understand the causes of PD and clinical trials to develop promising new therapies can only happen if people participate in the studies. Participating in a study can also help those living with Parkinson’s better understand their disease.
Current Medication Options
There are several medications available today designed to help manage various Parkinson’s symptoms. Most symptoms stem from a lack of the chemical dopamine in the brain. Many PD medicines either temporarily replenish dopamine or mimic its action.
Levodopa, which converts to dopamine, paired with carbidopa, is considered a first-line drug for improving movement challenges, such as tremor and slowness, and other PD movement symptoms. It can dramatically improve quality of life and can be delivered in a variety of formulations, including carbidopa/levodopa immediate, controlled and extended release, as well as preparations that can be inhaled or delivered through a surgically implanted tube in the small intestine. As Parkinson’s progresses, people may need to take levodopa more frequently to maintain good symptom control.
What are motor fluctuations, “wearing off” and “on-off” times?
Motor fluctuations are changes in the ability to move.
“On” time is when Parkinson’s medications (levodopa and dopamine agonists) take effect and you experience periods of good symptom control.
“Wearing off” is when the drugs begin to lose effect and there are periods where symptoms worsen and movement becomes more difficult, known as “off” time.
Other medications include:
- Monoamine oxidase-B (MAO-B) inhibitors that make more dopamine available in the brain to improve movement symptoms. These include rasagiline, selegiline and safinamide.
- Dopamine agonists to stimulate the parts of the brain influenced by dopamine — tricking the brain into thinking it is receiving the dopamine it needs. These include apomorphine, pramipexole, pramipexole ER, Ropinirole, Ropinirole XL and transdermal Rotigotine.
- Catechol-O-methyl transferase (COMT) inhibitors entacapone, tolcapone and opicapone, which help with changes in the ability to move as levodopa wears off. Carbidopa-levodopa-entacapone improves motor fluctuations while lengthening the benefits of levodopa.
- Antiglutamatergic medication amantadine. This can improve tremor and involuntary movements called dyskinesia that sometimes begin within a few years of taking levodopa. Its extended-release forms come in tablets and capsules.
- Anticholinergics benztropine, biperiden and trihexyphenidyl. These are used for tremor and dystonia, painful cramping, in younger people. However, research shows cognitive slowing is a side effect of anticholinergics. These medications can also cause confusion and hallucinations in older adults and should not be used in people over 70.
- Adenosine A2A antagonist istradefylline can reduce PD-related movement difficulties as levodopa wanes, known as “wearing off.”
People with PD can also experience a variety of non-movement symptoms, such as depression, anxiety, constipation, dizziness, hallucinations and more. The good news is that there are several prescription medications available for many of these symptoms.
Always talk to your Parkinson’s doctor about any medication concerns and side effects.
Room to Grow
There are several PD treatment options in the development pipeline. For some people with PD, current dopamine medicines fail to sufficiently address symptoms. Newer formulations that further improve and extend delivery are nearing approval. These drugs can minimize motor fluctuations and wearing off symptoms.
Two options for continuous levodopa infusion therapy are closer to getting the green light:
- ABBV-951: AbbVie has completed trials and filed for U.S. Food and Drug Administration (FDA) approval of a carbidopa/levodopa formulation designed for continuous delivery under the skin, which aims to increase “on” time by reducing motor fluctuations.
- ND0612: NeuroDerm recently completed clinical trials and is awaiting data on this new drug, which is a continuous subcutaneous carbidopa/levodopa infusion formula. The company expects to apply this year to U.S. and European regulatory industries for approval.
Studies have also been completed and published showing under-the-skin dopamine agonist apomorphine infusions can improve motor fluctuations in PD. Data has been submitted to the FDA for drug approval and is currently available in Europe.
For people newly diagnosed with Parkinson’s disease, P2B001 is a low-dose, extended-release formulation of pramipexole and rasagiline in development for the treatment of movement symptoms.
The FDA is reviewing Amneal’s IPX203, an extended-release carbidopa/levodopa tablet designed to extend PD symptom control while minimizing motor fluctuations.
In development, but further from the approval process, is Tavapadon, a once-daily tablet designed by Cerevel Therapeutics. It aims to target and activate certain dopamine receptors to improve PD motor symptoms while minimizing side effects sometimes related to other Parkinson’s therapies.
Putting the Brakes on PD
There is an active and ever-growing landscape of therapeutic trials aimed at slowing disease progression. In Parkinson’s, the protein alpha-synuclein misfolds and forms clumps in the brain called Lewy bodies. There are a number of experimental therapies in early development to either reduce alpha-synuclein production or minimize the forming of such clusters.
Though data from recent frontrunners targeting alpha-synuclein (prasinezumab and cinpanemab) failed to show slowing of PD progression, it can take decades to discover disease-modifying therapies.
A class of drugs approved to treat type 2 diabetes has also attracted a lot of attention for its potential to slow PD progression. Scientists across different studies in various stages of development are examining whether glucagon-like peptide-1 (GLP-1) receptor agonists can modify PD and improve symptoms.
Nilotinib, a drug approved for management of cancer, selectively inhibits tyrosine kinases, enzymes found in excess in some cancer cells. Tyrosine and other kinases have been linked to PD. Though studies of nilotinib did not improve PD biology, it was safe and tolerable in the small number of selected participants. Now, other novel cancer therapies are in the early stages of testing for potential effectiveness in PD.
There is also a lot of interest across neurodegenerative disease research in the gut-brain connection. This highlights the need for more studies that examine the role of inflammation in Parkinson's disease development.
PD and Personalized Medicine
Every person with Parkinson's experiences symptoms differently. Developing therapies to target the biology of PD in a particular individual is known as personalized medicine. Genetic targeting is the most advanced way to subtype drug development for people with PD.
While those with Parkinson’s who carry a PD-related gene mutation currently constitute a minority of people with Parkinson's, the biology that drives their disease can be relevant even to people who do not carry the same mutation.
Researchers are investigating possible therapeutic interventions for two PD-related genes:
- GBA, the most common Parkinson’s-related gene mutation, carried by up to 10% of people who live with the disease.
- LRRK2, the gene variants involved in about 1% of all PD diagnoses and 5% of those for people with a family history.
PD GENEration is a global initiative that offers comprehensive genetic testing and counseling for PD-related genes at no cost for people with Parkinson’s. It is critical to helping people determine whether they are candidates for gene-targeted medicine clinical trials. Knowledge of genetic status can also be important for therapeutic decision-making and for understanding individual disease progression, as well as potential implications for family.
Living Well Now
Taking control of the things you can early after diagnosis — creating healthy habits, embracing exercise and PD education and seeking out physical, occupational or speech therapy — can help address many aspects of Parkinson’s impacting your life right now.
Exercise, for example, is essential to managing many Parkinson’s symptoms and maintaining good function. Finding someone to talk to, such as a mental health therapist, can help you build coping skills and learn stress-easing strategies.
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