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Advances in Parkinson’s Treatment: From New Medications to Deep Brain Stimulation

(2024–2025 Update)
 For scientifically inclined readers—patients, care partners, and clinicians—who want a clear view of what’s new, what’s promising, and what’s next.

TL;DR (as of July, 2025)

  • New FDA‑approved options for motor fluctuations:
  • Procedures moved forward:
    • Adaptive (closed‑loop) deep brain stimulation (DBS)—first FDA‑cleared system that senses brain signals and self‑adjusts stimulation (Feb 2025). (Medtronic News, braininitiative.nih.gov)
    • Staged bilateral MR‑guided focused ultrasound (MRgFUS)—now FDA‑cleared to treat both sides (in two procedures months apart) for select patients with advanced PD (July 2025). (Focused Ultrasound Foundation, Insightec)
  • Near‑term pipeline: continuous levodopa ND0612 resubmission accepted by FDA (decision expected late 2025); tavapadon (D1/D5 partial agonist) met Phase 3 endpoints and is moving toward filing; cell therapies (e.g., BlueRock’s bemdaneprocel) entered/approaching Phase 3; disease‑modifying strategies (GLP‑1, α‑synuclein antibodies/ASOs, LRRK2) show mixed but advancing data. (Mitsubishi Tanabe Pharma America, AbbVie News Center, Reuters, ClinicalTrials.gov, GlobeNewswire)

1) What’s new—and why it matters

Smoother dopamine replacement. Crexont’s extended‑release design aims to reduce peaks and troughs from immediate‑release carbidopa/levodopa—important as gastric emptying slows and OFF periods emerge. (FDA Access Data)

Continuous dopaminergic delivery—without a surgical tube. Vyalev delivers levodopa equivalents through the skin 24/7, offering an alternative to intestinal gel pumps for advanced PD. Onapgo continuously infuses apomorphine (a dopamine agonist) to shrink daily OFF time. These options expand choices when oral schedules get complex. (FDA Access Data, AbbVie News Center)

Smart neuromodulation. Adaptive DBS reads local field potentials and automatically adjusts stimulation in real time. Early evidence and the ADAPT‑PD program underpinned FDA’s decision. For some, this can improve “good ON” control and may reduce side effects or battery use compared with fixed stimulation. (Medtronic News, braininitiative.nih.gov)

Incisionless lesioning goes bilateral (staged). MRgFUS—once unilateral—now has staged bilateral approval at specialized centers (two sessions, months apart) for select patients, broadening non‑implant options when tremor or dyskinesia dominate and medications/DBS aren’t suitable. (Focused Ultrasound Foundation, Insightec)

2) Medications & infusion therapies

A. Levodopa innovations

  • Crexont® (carbidopa/levodopa ER)—FDA label confirms a multiparticulate design (IR granules + ER pellets). It’s meant to extend benefit with fewer daily doses vs IR CD/LD. Clinically, expect standard levodopa effects/risks; titration remains individualized. (FDA Access Data)
  • Vyalev™ (foslevodopa/foscarbidopa)—24‑hour SC infusion of levodopa prodrugs. Pivotal data supporting approval showed improvements in “ON time without troublesome dyskinesia” vs optimized oral therapy. Ideal for advanced fluctuations when oral absorption is erratic. (AbbVie News Center)
  • ND0612 (continuous SC levodopa/carbidopa)—after a 2024 complete response letter, the sponsor resubmitted; FDA accepted in May 2025 (decision anticipated by year‑end). Phase 3 and long‑term studies suggest added “good ON” and reduced variability; if approved, ND0612 would join Vyalev/Onapgo as a third under‑the‑skin option. (Neurology live, Mitsubishi Tanabe Pharma America, Michael J. Fox Foundation)

B. Continuous dopamine agonist

  • Onapgo™ (apomorphine infusion)—first FDA‑cleared continuous apomorphine system (subcutaneous pump) for adults with advanced PD and OFF episodes; label details pump‑specific safety/monitoring. Consider for patients who respond to apomorphine but need steadier delivery. (FDA Access Data, Reuters)

C. Next‑in‑class receptor pharmacology

  • Tavapadon (selective D1/D5 partial agonist)—Across Phase 3 studies (TEMPO‑1/‑2/‑3), tavapadon improved motor ratings and increased good ON time as adjunct to levodopa; AbbVie signaled 2025 regulatory plans. If approved, it would be the first drug in its class for PD. (Reuters, AbbVie News Center, Practical Neurology)

Where these fit:

  • Earlier PD: Crexont vs. IR CD/LD to simplify routines; consider tavapadon (pending approval) for motor control with a distinct receptor profile.
  • Advancing PD with fluctuations: Vyalev, ND0612 (if approved), or Onapgo may help when gastric variability sabotages pills.

3) Devices & procedures

A. DBS 2.0—directional, sensing, adaptive

  • Directional leads can “steer” current to widen the therapeutic window and limit side effects, though trial results differ on magnitude; many centers now program directionality routinely. (JNNP, PMC, Nature)
  • Sensing‑enabled DBS (Percept™ RC/PC) brought chronic brain signal recording into standard care (US clearance Jan 2024). (Medtronic News)
  • Adaptive DBS (aDBS)—FDA‑cleared Feb 2025 via a software/hardware update that activates the closed‑loop algorithm in Percept systems. The NIH BRAIN Initiative notes the ADAPT‑PD clinical program supporting approval. Clinically, aDBS may smooth fluctuations and reduce programming burden for select candidates; not all patients need (or benefit from) closed‑loop control. (FDA Access Data, braininitiative.nih.gov)

B. Focused ultrasound (MRgFUS)

  • Staged bilateral approval (July 2025) allows treatment on both sides—performed months apart—to address disabling tremor/dyskinesia in carefully selected patients. Benefits are immediate; risks include gait/speech changes and are irreversible (unlike DBS). Shared decision‑making is essential. (Focused Ultrasound Foundation, Insightec)

Choosing between DBS and MRgFUS (practical frame):

  • DBS (STN or GPi): adjustable, reversible, bilateral in one surgery; now includes adaptive options.
  • MRgFUS: incisionless, outpatient; now staged bilateral but not adjustable once lesions are made.
    Talk candidly about goals (tremor vs rigidity/bradykinesia), cognitive status, gait/speech risks, and local expertise.

4) What’s moving the disease‑modifying needle?

Bottom line: promising signals, but no approved disease‑modifying therapy yet.

GLP‑1 receptor agonists (metabolic pathway):

  • Lixisenatide (LixiPark) Phase 2: slowed motor worsening over 12 months vs placebo (NEJM Apr 2024); GI side effects common; larger/longer trials needed. (PubMed, Gwern)
  • Exenatide Phase 3 (2024/2025): negative—no slowing of progression vs placebo. Expert groups caution against off‑label use of current GLP‑1s for disease modification pending more data. (Parkinson’s UK, University College London, Parkinson’s Foundation)

α‑Synuclein immunotherapy:

  • Prasinezumab Phase 2b (PADOVA) missed the primary endpoint but showed trends suggesting possible benefit in subgroups; Roche plans a Phase 3 program (announced June 16, 2025). (Roche)
  • Active vaccination (UB‑312) achieved CSF target engagement in early trials; larger efficacy studies are in progress. (Nature, Vaxxinity)

LRRK2 pathway (genetics‑informed):

  • Small‑molecule LRRK2 inhibitors (Denali/Biogen BIIB122) continue in Phase 2 programs (LUMA/BEACON) with biomarker‑rich designs; outcome data are pending. ASO approaches (Ionis ION859/BIIB094) reduced CNS LRRK2 protein in Phase 1, supporting continued development. (ClinicalTrials.gov, BioSpace, Parkinson’s News Today)

Cell & gene therapy:

  • Cell replacement
    • Bemdaneprocel (BlueRock)—embryonic stem cell–derived dopaminergic neurons: Nature 2025 reported 18‑month Phase 1 data with survival/engraftment signals and acceptable safety; a Phase 3, sham‑controlled trial (exPDite‑2) is moving forward. (Nature, ClinicalTrials.gov, GlobeNewswire)
    • Autologous iPSC (Aspen Neuroscience ANPD001)—first patients dosed in 2024; initial 6‑month data from the first cohort reported in 2025 (early safety/feasibility). (Aspen Neuroscience, PR Newswire)
    • Allogeneic iPSC (Kyoto group)—Phase I/II trial reported increased putaminal ^18F‑DOPA uptake and acceptable safety over 24 months, signaling biological activity. (PubMed)
  • Gene therapy
    • GBA1‑targeted AAV9 (PR001 / LY3884961)—Phase 1/2 open‑label trial for PD with GBA1 mutations continues enrollment; no efficacy readout yet. (Prevail Therapeutics, MedPath)
    • Historic AADC/gene replacement programs were discontinued earlier; lessons learned inform current vector/safety strategies. (Neurology live)

5) Quick guide: matching options to common scenarios

ScenarioConsider
Early PD, motor symptoms emergingOptimize levodopa; consider Crexont for smoother coverage; watch tavapadon (pending regulatory review). (FDA Access Data, AbbVie News Center)
Troublesome OFF periods despite best pill regimenVyalev (24‑h levodopa prodrugs), Onapgo (apomorphine infusion); ND0612 may follow if approved. (AbbVie News Center, FDA Access Data, Mitsubishi Tanabe Pharma America)
Medication works, but side effects or fluctuations persistDBS (now sensing/adaptive‑capable) after candidacy work‑up; staged bilateral MRgFUS if implantless option preferred and candidacy fits. (Medtronic News, braininitiative.nih.gov, Focused Ultrasound Foundation)
Interest in research that could slow progressionDiscuss GLP‑1 trials beyond exenatide, prasinezumab Phase 3, LRRK2/ASO studies, and cell/gene trials—eligibility often depends on genetics, stage, and center access. (PubMed, Roche, ClinicalTrials.gov)

6) Action steps (patient‑ and clinician‑friendly)

  1. Map priorities. Is the goal fewer OFF hours, less dyskinesia, simpler dosing, or reducing caregiver task load? This clarifies whether to escalate meds, consider infusion, or consult for DBS/MRgFUS.
  2. Ask focused questions at visits:
  • “Would Crexont’s ER profile simplify my schedule?” (Bring a diary of *ON/OFF). (FDA Access Data)
  • “Am I a candidate for Vyalev or Onapgo?” (Consider skin, nausea risk, support for pump care). (FDA Access Data)
  • “Do the benefits/risks of aDBS vs conventional DBS apply to my pattern of fluctuations?” (Center experience matters). (Medtronic News)
  • “If I can’t have an implant, could staged bilateral MRgFUS be appropriate?” (Discuss speech/gait considerations). (Focused Ultrasound Foundation)
  1. Consider research participation. If you have GBA1 or LRRK2 variants—or are early in disease—ask about targeted trials (prasinezumab Phase 3; LRRK2 inhibition/ASO; cell therapy programs). (Roche, ClinicalTrials.gov)

7) How Aqualane Research can help

Aqualane Research pre‑screens interested patients and care partners for suitable clinical studies (by stage, genetics, symptom profile, and geography) and prepares clinician‑friendly summaries you can take to your neurologist. If you’d like that support, tell us:

  • Your main goals (e.g., cut OFF time, reduce dyskinesia, simplify meds)
  • Current regimen and two‑day *ON/OFF diary
  • Whether you’ve had genetic testing (GBA1, LRRK2, others)
    We’ll match you to appropriate trials and help you prepare questions for your next visit.

Key references you can share with your care team

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