Could a Weekly Injection Replace Daily Pills for Parkinson’s Care?

Parkinson’s disease, a progressive neurodegenerative condition that affects over 10 million people worldwide, has long required a daily routine of oral medications to manage symptoms. But a breakthrough therapy in development could change everything—a once-weekly injection of PEG‑levodopa, designed to replace the need for multiple daily doses of standard levodopa pills. This innovation holds the promise of improving both quality of life and treatment adherence for patients battling this chronic illness.

At betterhealthfacts.com, we delve into this emerging therapy to understand how it works, what its clinical implications are, and how close we may be to a new standard of Parkinson’s care.

Understanding Parkinson’s Disease and the Role of Levodopa

Parkinson’s disease is characterized by the gradual death of dopamine-producing neurons in the substantia nigra, a part of the brain responsible for movement control. The resulting dopamine deficiency leads to hallmark symptoms such as tremors, bradykinesia (slowness of movement), rigidity, and postural instability.

For decades, the gold standard treatment has been levodopa, a precursor of dopamine that can cross the blood-brain barrier. Once inside the brain, it is converted into dopamine, replenishing the neurotransmitter and improving motor function. Levodopa is often administered in combination with carbidopa, which prevents its premature breakdown outside the brain and reduces side effects.

However, oral levodopa has a relatively short half-life (about 90 minutes) and requires frequent dosing—typically three to six times daily. This can make adherence challenging, especially in advanced stages of Parkinson’s when cognitive and motor decline may interfere with medication schedules.

The Innovation: PEG‑Levodopa Gel

PEG‑levodopa is a new formulation that combines levodopa with polyethylene glycol (PEG), a long-chain molecule that alters the pharmacokinetics of the drug. This PEGylation technique allows the levodopa to be released slowly over time, enabling sustained plasma levels of the medication with once-weekly subcutaneous injection.

This technology is being developed by biotechnology firm NeuroDerm (a subsidiary of Mitsubishi Tanabe Pharma). The investigational drug, known in trials as ND0612-PEG, has been formulated into a gel that can be injected beneath the skin, providing a controlled and extended release of levodopa over seven days.

“PEGylation has been a proven delivery platform in other therapeutic areas, and applying it to Parkinson’s management could significantly reduce pill burden and improve treatment compliance,” says Dr. Avraham Israeli, former director general of Israel's Ministry of Health and advisor to NeuroDerm.

Why Daily Pills Can Be Problematic for Parkinson’s Patients

Oral medications, though effective, come with inherent limitations:

• Motor fluctuations: Peaks and troughs in plasma levodopa levels can cause periods of "on" and "off" symptoms throughout the day.
• Dyskinesias: Excessive or erratic levodopa levels can lead to involuntary movements.
• Adherence issues: As the disease progresses, cognitive impairment or tremors can make swallowing or remembering doses difficult.
• Gastrointestinal complications: Gastroparesis, common in Parkinson’s, affects absorption of oral levodopa.

A once-weekly injection could potentially eliminate many of these issues by stabilizing drug levels over longer periods, reducing symptom fluctuations and increasing patient independence.

How the PEG‑Levodopa Gel Works

The PEG‑levodopa formulation uses a hydrogel that releases levodopa slowly into the bloodstream after subcutaneous injection. PEG molecules create a lattice-like network that slows the diffusion of the drug, allowing for extended duration of action. This approach aims to mimic the continuous dopamine stimulation theory—providing a steady stream of levodopa rather than abrupt peaks and valleys.

Continuous delivery of levodopa has previously been attempted through intrajejunal infusions (e.g., Duopa), but those require a surgically implanted pump and are associated with risks like infection or tube dislodgement. PEG‑levodopa avoids this invasive delivery by enabling simple weekly self-injection.

“We believe this is the first truly practical long-acting levodopa delivery system that offers both convenience and pharmacological stability,” notes Dr. Shlomo Lahat, CMO of NeuroDerm.

Early Trial Results: Promising but Preliminary

In preclinical and early-phase trials, PEG‑levodopa has demonstrated the ability to maintain therapeutic levels of levodopa in plasma over the full week. Participants showed reduced motor fluctuation and improved "on" time without increasing dyskinesias.

Though formal Phase 3 trial results are pending, Phase 2 studies have been encouraging:

• Stable levodopa plasma levels over 7 days
• Decreased reliance on rescue medications
• Good tolerability with minimal injection site reactions
• No serious adverse events linked directly to the drug

One small open-label study found that patients experienced over 40% reduction in “off” time and increased independence in daily tasks over a 12-week period.

Impact on Medication Adherence and Lifestyle

Medication adherence is a significant barrier in managing chronic diseases. In Parkinson’s, non-adherence to levodopa therapy has been linked to worsening symptoms, more frequent hospitalizations, and reduced quality of life.

Switching to a weekly injection format could transform patient experience in several ways:

• Improved adherence: Fewer doses mean fewer missed medications.
• Reduced caregiver burden: Less frequent supervision needed for dosing.
• Greater lifestyle flexibility: Travel and daily routines less interrupted by pill schedules.
• Improved patient satisfaction: Consistent control of motor symptoms can boost morale and engagement.

“A weekly levodopa injection could be a game-changer for many of my patients who struggle with complex medication schedules,” says Dr. Irene Litvan, director of the Movement Disorder Center at UC San Diego.

Regulatory Pathway and Timeline to Approval

The development of PEG‑levodopa is currently in advanced clinical trial stages. NeuroDerm announced completion of Phase 2b trials in early 2025 and is preparing for large-scale Phase 3 trials across the U.S., Europe, and Asia.

If results continue to show positive outcomes, regulatory submissions to the FDA and EMA could occur by late 2026, with potential market approval by 2027 or 2028.

The drug will need to demonstrate:

• Non-inferiority or superiority to standard oral therapy
• Safety profile comparable to existing levodopa regimens
• Patient-reported outcomes showing improved quality of life

What Are the Risks or Limitations?

Despite the enthusiasm, some challenges and unanswered questions remain:

• Long-term safety of subcutaneous PEG formulations
• Injection site irritation with repeated use
• Higher cost compared to generic oral levodopa
• Acceptance among patients and providers resistant to injectables

Further research will also need to assess how PEG‑levodopa performs in different stages of Parkinson’s, from early onset to late-stage disease, and how it interacts with other standard medications like dopamine agonists or MAO-B inhibitors.

The Future of Parkinson’s Treatment: Beyond Oral Pills

The development of PEG‑levodopa reflects a broader trend in neurology and chronic disease management: moving away from multiple daily pills toward long-acting, patient-friendly delivery systems. Weekly injections, wearable patches, and even intranasal delivery are all under investigation to make therapies more accessible and reliable.

For Parkinson’s, the ability to provide smooth, continuous dopamine stimulation could not only improve symptom control but potentially slow disease progression—though more evidence is needed to confirm this.

Conclusion

Could a weekly injection replace daily pills for Parkinson’s care? Based on current science, the answer seems increasingly promising. The PEG‑levodopa gel offers a potentially transformative approach that aligns with patient preferences, reduces complications from fluctuating drug levels, and encourages better adherence. Though further trials are essential to validate its efficacy and safety, the concept represents a crucial step toward modernizing Parkinson’s disease management.

As new data emerge and regulatory pathways unfold, betterhealthfacts.com will continue to track this exciting development. If approved, this weekly injection could fundamentally change how we treat one of the world’s most challenging neurodegenerative diseases.