Parkinson’s Disease: Advances in Diagnosis and Treatment

An estimated 1 million people in the US have Parkinson’s disease, and about 90,000 new diagnoses are made each year. Even though approximately 90% of people with Parkinson’s in the US are insured by Medicare, 40% have not seen a neurologist, according to an analysis of healthcare utilization patterns in 2019. And only 9.1% visited a movement disorder specialist. As a result, primary care physicians provide much of the routine care for these patients.

“We rely heavily on our primary care colleagues,” said Rebecca Gilbert, MD, PhD, a neurologist and chief mission officer for the American Parkinson Disease Association, a grassroots organization dedicated to fighting the disease.

Several recent developments in the diagnosis and treatment of Parkinson’s disease are worth the attention of primary care, according to Dr. Gilbert, as detailed below.

New Biomarker Tests Support Earlier Parkinson’s Diagnosis

Traditionally, a Parkinson’s diagnosis is made clinically, Dr. Gilbert explained. After a physical exam, a physician would have the patient move their arms and legs and observe them walking, looking for classic motor symptoms of the disorder. “That’s not going to go away,” she said.

However, in these scenarios, diagnosis is only made once symptoms are present. “Tests have been developed now, which are commercially available, to test for biologic markers [present before the motor symptoms],” Dr. Gilbert said.

For example, SYNTap, an alpha-synuclein seed amplification assay (aSyn-SAA), detects misfolded or clumped alpha-synuclein proteins in the cerebrospinal fluid; misfolded aggregates of this protein in the brain are a hallmark of Parkinson’s disease.

The aSyn-SAA test has a 93% accuracy and has been validated through the Parkinson's Progressive Markers Initiative (PPMI), led by the Michael J. Fox Foundation for Parkinson’s Research, said Brian Fiske, PhD, chief scientific officer for the foundation.

The test, he told MedCentral, "allows us for the first time to measure the biology that is occurring in Parkinson’s disease. We’ve long known that abnormal alpha-synuclein clumps in the brains of people living with Parkinson’s through post-mortem analysis, but this is the first time where we can measure it in a living human person.” That translates to the possibility of treating the disease earlier and eventually preventing it altogether as more discoveries are made.

The FDA granted aSyn-SAA breakthrough device status in 2019; a physician must order the test.

Another diagnostic test is a skin biopsy test, Syn-One, that looks for abnormal alpha-synuclein; one study found it to be early 93% accurate in detecting Parkinson’s. Classified as a laboratory-developed test, the Syn-One does not require FDA approval; it can be used by clinicians.

An imaging test called DaT scan (dopamine transporter scan) was approved by the FDA over a decade ago.

However, Dr. Gilbert said, experts are still trying to determine which patients should get these tests and how their use should be incorporated into the diagnosis.

FDA-Approved Treatments for Parkinson’s Disease

In the past 10 years, approximately 19 new treatments have been approved for Parkinson’s disease, according to Dr. Fiske. Among the currently available treatments are medications for motor symptoms (eg, dopamine replacement therapies) and non-motor symptoms (eg, constipation and memory issues), deep brain stimulation to decrease the needed dose of medication, and ultrasound therapy for when deep brain stimulation doesn’t work.

Levodopa is the first-line medication for Parkinson’s disease. Absorbed by the brain’s nerve cells and converted to dopamine, the drug transmits messages that control movement and helps patients to manage difficulties with walking, movement, and tremors.

FDA approved a new formulation of carbidopa/levodopa (Crexont) this month. The medication contains both immediate-release granules and extended-release pellets, according to manufacturer Amneal Pharmaceuticals. “When you have Parkinson’s, you can get sensitive to medications, and they work for shorter periods of time,” Dr. Gilbert said, explaining the need for extended-release formulations.

Promising Pipeline for Parkinson’s

Several treatments are in late-stage trials or under FDA review, including three subcutaneous formulations:

• Supernus’s continuous apomorphine infusion (SPN-830) is similar to an insulin pump; a PDUFA date is set for February 2025.

• NeuroDerm’s ND0612 provides continuous levodopa/carbidopa infusion through an insulin-pump device; the US FDA issued a Complete Response Letter (CRL) to NeuroDerm in June and the company plans to resubmit its NDA.

• Abbvie’s foslevodopa/foscarbidopa (ABBV-951, Produoopa) for severe motor flucations in those with advanced Parkinson’s disease was approed by the European Union in January, however, the US FDA issued the company a CRL in June; the company also plans to resubmit its NDA.

Continuous infusion formulations such as these aim to reduce fluctuations in the levels of dopamine that can occur in people with Parkinson's when the effects of oral medicine wear off and movement becomes stiffer.

Overall, said Dr. Fiske, the Foundation is tracking more than 150 therapeutic approaches in the clinical pipeline, from Phase 1 through 3. “It’s the most robust and diverse pipeline of different programs and clinical trials that we’ve ever seen,” he said. More details about those trials are here.

Experts are also questioning whether diabetes medications, such as semaglutide (Ozempic), might be neuro-protective, Dr. Gilbert said.

A vaccine meant to train the body to recognize abnormal forms of the alpha synuclein protein is under study as well. A Phase 1 trial found that participants who got the vaccine produced more antibodies against the abnormal alpha synuclein protein than participants who received the placebo.

Speeding Drug Development & Genetic Testing

Multiple efforts are underway to speed the progress of drugs from Phase 2 to Phase 3 study, said Rosie Fuest, research manager at Cure Parkinson’s, a UK-based organization that funds research and clinical trials. One approach involves a multi-arm, multi-stage platform trial that will facilitate testing of multiple drugs simultaneously against one placebo group with interim analyses ensuring that drugs not showing efficacy can be replaced by others.

Genetic forms of Parkinson’s disease are rare, accounting for about 10% to 15% of cases, said James Beck, PhD , chief scientific officer of the Parkinson’s Foundation, New York City. However, “a number of companies are working on therapies that will target the genetic mutation[that leads to Parkinson’s].”

More than 90 gene variants have been identified and associated with Parkinson’s to date. The Parkinson’s Foundation offers people with the disease genetic testing and counseling at no cost if they enroll in the PD GENEration Study. Knowing about a genetic mutation can help determine eligibility for clinical trials. Picture Genetics also offers the genetic test as an at-home Parkinson’s risk screening test, Dr.Beck said. The out-of-pocket cost is $595.

Those with Parkinson’s can also get involved in research in ways that don’t require an intervention, Fuest said, such as participation in observational studies or online surveys. “It is important that, after diagnosis, people with Parkinson’s are given an opportunity to learn about how to get involved in research,” she said. “This includes how to find opportunities, such as through sites in the US like the Fox Trial Finder, guidance on who to discuss this with, and benefits to taking part that extend beyond access to a new drug.”

Resources for Primary Care Physicians

Dr. Beck notes that primary care physicians are not alone, pointing to Parkinson’s Foundation services. Their helpline((800-4PD-INFO), for instance, “can take the burden off a busy practitioner.” Physicians may also wish to refer patients seeking more information to the American Parkinson Disease Association and Cure Parkinson's websites.

When possible, added Dr. Gilbert, refer patients to a movement disorder specialist. Even a one-time appointment could be helpful, she said.

Disclosures: Dr. Gilbert, Dr. Beck, Dr. Fiske, and Fuest reported no conflicts of interest.