Overview

Parkinson’s disease (PD) is a progressive neurological disorder that affects movement and many non-motor systems, including sleep, mood, cognition, smell, digestion, bladder function, and blood-pressure regulation. It is diagnosed clinically by recognizing a characteristic parkinsonian syndrome and excluding disorders that can look similar.¹²

Typical PD involves degeneration of dopamine-producing neurons in the substantia nigra and, in most sporadic cases, abnormal aggregation of the protein α-synuclein in the nervous system. The biology is heterogeneous: not every person has the same genetic background, distribution of pathology, symptom pattern, biomarker profile, or rate of progression. Parkinson’s should therefore not be reduced to tremor alone or to a single laboratory result.¹³

There is no cure and no treatment has yet been proven to stop or slow the underlying disease. Even so, PD is often highly treatable symptomatically. Levodopa, other medications, exercise, rehabilitation, treatment of non-motor symptoms, and advanced therapies can substantially improve function and quality of life.

The most important Parkinson’s updates are:

• α-Synuclein biomarkers are changing research and selected diagnostic evaluations. Cerebrospinal-fluid seed amplification assays (SAA) and skin biopsy for phosphorylated α-synuclein can detect Lewy-related biology in many patients. They can support an evaluation, but they do not replace the history and neurological examination, do not by themselves determine prognosis or treatment, and are not uniquely positive only in Parkinson’s disease.³⁴⁵
• Biological staging systems remain research frameworks. The NSD-ISS and SynNeurGe proposals were designed to make clinical trials more biologically precise. They are not replacements for current clinical diagnostic criteria and should not be used to label an asymptomatic person as having clinical Parkinson’s disease outside an appropriate research or specialist context.⁷⁸
• Motor-fluctuation treatment now includes more continuous delivery options. Crexont® is an extended-release oral carbidopa/levodopa capsule; Vyalev® is a continuous subcutaneous foscarbidopa/foslevodopa infusion for adults with advanced PD and motor fluctuations; and Onapgo™ is a continuous subcutaneous apomorphine infusion for adults with advanced PD and motor fluctuations.¹²¹³¹⁴
• Carbidopa/levodopa labeling now includes vitamin B6 monitoring. In March 2026, the FDA required warnings that carbidopa/levodopa therapies may contribute to vitamin B6 deficiency and associated seizures. Current labeling recommends evaluation before treatment, periodically during treatment, and when clinically indicated, with supplementation when levels are low.¹⁵
• Adaptive deep brain stimulation is now FDA approved as an optional programming feature. The system senses selected brain signals and adjusts stimulation within clinician-programmed limits. It does not make DBS appropriate for everyone and does not remove the need for surgery, programming, medication adjustment, and specialist follow-up.¹⁶
• Focused ultrasound has a broader but still specific Parkinson’s indication. FDA labeling now allows staged treatment of the opposite side at least six months after the first procedure in selected adults with advanced idiopathic PD and medication-refractory motor complications. Focused ultrasound creates a permanent thermal brain lesion; it is not adjustable or reversible like DBS.¹⁷
• Tavapadon has positive Phase 3 data but remains investigational. Randomized trials published in 2026 reported benefit as monotherapy in early PD and as an add-on to levodopa in patients with motor fluctuations. A U.S. new drug application was submitted in 2025, but tavapadon was not FDA approved as of this article’s evidence cutoff.^22232425
• Cell-replacement therapy has entered an important but very early clinical phase. Small open-label studies show that transplanted dopamine-cell progenitors can survive and produce imaging evidence of dopamine function. These studies are not proof of efficacy. They involve brain surgery, and allogeneic products have required immunosuppression; in the 2026 eight-participant STEM-PD report, one participant died from disseminated fungal infection while immunosuppressed.²⁸²⁹

Evidence cutoff: This article reflects publicly available evidence through August 9, 2026. Regulatory status, prescribing information, and research findings can change. Sponsor-reported, newly presented, and early-phase results are identified as such and should not be interpreted as established clinical benefit.

---

Understanding Parkinson’s Disease

What Changes in the Nervous System

Movement symptoms arise largely from loss of dopaminergic signaling in circuits connecting the substantia nigra, striatum, thalamus, and cortex. These circuits help initiate movement, scale its speed and amplitude, and make routine movements automatic. Dopamine loss can therefore produce slowness, reduced movement size, stiffness, and tremor.

PD also affects nondopaminergic pathways and the peripheral autonomic nervous system. This broader involvement helps explain why constipation, sleep disturbance, loss of smell, depression, pain, fatigue, urinary symptoms, orthostatic hypotension, hallucinations, and cognitive change can be as important as the motor symptoms.¹

Lewy bodies and Lewy neurites containing abnormal α-synuclein are characteristic of most sporadic PD, but Parkinson’s biology is not uniform. Some genetic forms have less detectable α-synuclein seeding, and Lewy-related pathology also occurs in dementia with Lewy bodies, multiple system atrophy, pure autonomic failure, and in some people with other neurological diseases. This is one reason a positive biomarker is not synonymous with a complete clinical diagnosis.³⁴⁵

Symptoms Can Begin Before the Motor Diagnosis

Loss of smell, constipation, depression, autonomic symptoms, and REM sleep behavior disorder can precede the motor syndrome by years. These symptoms are common in the general population and do not by themselves diagnose Parkinson’s disease. REM sleep behavior disorder—recurrent dream enactment due to loss of normal REM-sleep muscle paralysis—is a particularly important risk marker for future synucleinopathy, but its evaluation should also consider medication effects, sleep apnea, and other sleep disorders.

“Brain-First” and “Body-First” Are Proposed Models

The brain-first/body-first model proposes that Lewy-related pathology may begin in different anatomical locations in different people. In a proposed body-first pattern, early autonomic and REM-sleep features may precede more asymmetric motor disease; in a proposed brain-first pattern, pathology may begin centrally and produce a different sequence. This is an active research model, not a clinically validated test or a basis for choosing routine treatment.⁹

Risk Factors and Genetics

• Age: risk rises with age, although young-onset PD can occur.
• Sex: PD is diagnosed more often in men than women, but it affects all sexes.
• Genetics: variants in genes including GBA1, LRRK2, PRKN, PINK1, and SNCA can influence risk or cause familial forms. Most people with PD do not have a single clearly causative variant.
• Environmental and occupational exposures: epidemiological studies associate certain pesticides, solvents, and other exposures with risk, but an exposure history rarely establishes the cause in an individual patient.

Genetic counseling and testing may be reasonable for younger-onset disease, a strong family history, particular ancestry, atypical features, or clinical-trial eligibility. A genetic result may affect family counseling and research options, but usually does not predict an individual’s exact course.

---

Symptoms of Parkinson’s Disease

Core Motor Features

Bradykinesia is the required motor feature of parkinsonism. On examination, it means slowness accompanied by progressively smaller or less effective repeated movements. For a diagnosis of parkinsonism, bradykinesia is combined with rest tremor, rigidity, or both.²

• Bradykinesia: difficulty initiating movement, reduced arm swing, smaller handwriting, slower dressing or eating, reduced facial expression, and reduced speed or amplitude with repetitive finger or foot movements.
• Rest tremor: rhythmic shaking that is often most noticeable when the limb is relaxed and may decrease during purposeful movement. Tremor is not required, and some patients never develop it.
• Rigidity: increased resistance to passive movement that can contribute to stiffness, aching, reduced arm swing, and restricted range of motion.
• Gait and balance change: short steps, shuffling, reduced foot clearance, difficulty turning, freezing, and later postural instability. Prominent falls very early in the course are a reason to consider an atypical parkinsonian disorder.

Other motor manifestations include soft speech, reduced facial animation, drooling, swallowing difficulty, flexed posture, toe or foot dystonia, and freezing of gait. Symptoms often begin asymmetrically, but asymmetry alone does not prove PD.

Non-Motor Symptoms

• Loss of smell
• Constipation, slowed stomach emptying, or unintentional weight loss
• Urinary urgency, frequency, or nighttime urination
• Orthostatic hypotension, lightheadedness, or fainting
• REM sleep behavior disorder, insomnia, excessive daytime sleepiness, or restless legs symptoms
• Depression, anxiety, apathy, or irritability
• Fatigue, pain, sweating, sexual dysfunction, and temperature intolerance
• Hallucinations, cognitive impairment, or dementia in some patients, usually later in the course

Non-motor symptoms should not automatically be attributed to PD. Infection, dehydration, sleep apnea, anemia, thyroid disease, medication effects, mood disorders, primary urologic or gastrointestinal disease, and other conditions may require separate evaluation.

Motor Fluctuations and Dyskinesia

Levodopa often produces a strong and relatively smooth response early in the disease. With disease progression, a dose may wear off before the next dose, morning “off” periods may lengthen, or benefit may become less predictable. Patients can also develop dyskinesia—involuntary twisting or flowing movements that often occur when levodopa effect is high, although diphasic and off-period dyskinesias also occur.

“Off” periods can include non-motor symptoms such as anxiety, pain, sweating, cognitive slowing, or shortness of breath in addition to worsening movement. A diary that records medication times, meals, on time, off time, dyskinesia, sleep, and falls can help distinguish inadequate dose, short duration of benefit, delayed absorption, and other patterns.

---

How Parkinson’s Disease Is Diagnosed in 2026

The Diagnosis Is Still Clinical

A movement-disorders history and examination remain the foundation. The clinician confirms parkinsonism, looks for supportive features such as a clear levodopa response, and assesses exclusion criteria or red flags for a different diagnosis. A levodopa response supports PD but is not perfectly specific; absence of an obvious response can reflect an inadequate trial, poor absorption, incorrect timing, advanced axial symptoms, or a different disorder.²

Features that may suggest an atypical or secondary parkinsonian disorder include early recurrent falls, early severe autonomic failure, early prominent speech or swallowing impairment, vertical gaze limitation, cerebellar signs, corticospinal signs, marked apraxia or cortical sensory loss, rapid progression, symmetric lower-body-predominant disease, exposure to dopamine-blocking drugs, or little benefit from an adequate levodopa trial.

MRI and DaTscan

• Brain MRI is often normal or nonspecific in typical PD. It is used primarily to evaluate alternative or contributing causes such as stroke, hydrocephalus, tumor, structural disease, or imaging patterns associated with atypical parkinsonism.
• DaTscan™ (ioflupane I 123 SPECT) is an adjunctive test that demonstrates presynaptic dopaminergic deficit. It can help distinguish a degenerative parkinsonian syndrome from conditions such as essential tremor or some forms of drug-induced parkinsonism. It does not reliably distinguish PD from multiple system atrophy, progressive supranuclear palsy, or other degenerative parkinsonian disorders.¹⁰

Neither MRI nor DaTscan should be ordered automatically for every patient. Testing is most useful when it answers a specific unresolved diagnostic question.

CSF α-Synuclein Seed Amplification Assay

In the 1,123-participant Parkinson’s Progression Markers Initiative analysis, CSF α-synuclein SAA was positive in 87.7% of participants with clinically diagnosed PD and negative in 96.3% of healthy controls. Sensitivity was 98.6% in typical sporadic PD with loss of smell, but lower in LRRK2-associated PD and in sporadic PD without olfactory deficit. These differences show both the power and the limitations of the assay.⁴

A positive SAA indicates detectable seeding activity consistent with Lewy-related α-synuclein biology. It does not by itself distinguish PD from every other synucleinopathy, determine disease stage, prove that current symptoms are caused by PD, or predict an individual’s response to treatment. The FDA has issued a Letter of Support for SAA as a clinical-trial enrichment biomarker; a Letter of Support is not the same as FDA qualification or approval as a standalone diagnostic test.⁶

Skin Biopsy for Phosphorylated α-Synuclein

In a 2024 multicenter cross-sectional study of carefully selected participants with expert-confirmed diagnoses, phosphorylated α-synuclein was detected in 92.7% of participants with PD, 98.2% with multiple system atrophy, 96.0% with dementia with Lewy bodies, and 100% with pure autonomic failure, compared with 3.3% of controls. The test therefore identified synucleinopathy biology but was not specific to Parkinson’s disease.⁵

Clinical interpretation requires attention to biopsy sites, laboratory method, pretest probability, alternative synucleinopathies, and the possibility of false-positive or false-negative results. The published study called for validation in broader, unselected clinical populations.

What Biomarkers Can and Cannot Do

• They can add biological support when the clinical diagnosis is uncertain.
• They may help select participants for research aimed at α-synuclein biology.
• They cannot replace the neurological examination or distinguish every cause of parkinsonism.
• They do not currently determine whether a person should start levodopa, undergo DBS, or receive a particular routine medication.
• A negative result does not completely exclude PD, especially in certain genetic or olfaction-preserved subgroups.

NSD-ISS and SynNeurGe

The 2024 NSD-ISS and SynNeurGe systems propose classifying disease using combinations of pathological α-synuclein, neurodegeneration, genetics, and clinical manifestations. Their purpose is to improve research cohorts and enable trials earlier in the biological course. Both publications emphasize research use. As of 2026, there is no consensus that these frameworks should replace clinical diagnosis or be used for population screening.⁷⁸³

---

Treatment and Management

Treatment is based on which symptoms interfere with function or quality of life, the patient’s age and medical history, work and driving needs, cognitive and psychiatric status, fall risk, prior response, and preferences. No single sequence fits everyone.

Levodopa Remains the Most Effective Motor Medication

Carbidopa/levodopa remains the most effective medication for bradykinesia and rigidity and often helps tremor. The American Academy of Neurology guideline recommends levodopa as the preferred initial dopaminergic therapy for most patients seeking treatment for early motor symptoms, while using the lowest effective dose and monitoring for dyskinesia, fluctuations, hallucinations, sleepiness, and orthostatic hypotension.¹¹

Starting levodopa is generally driven by symptoms and function rather than by a need to “save it for later.” Levodopa does not treat every PD symptom: balance impairment, freezing that is not levodopa-responsive, speech changes, autonomic symptoms, cognition, and sleep problems may require other strategies.

Formulations include immediate-release tablets, orally disintegrating tablets, controlled or extended-release products, the extended-release Crexont capsule, inhaled levodopa for selected off episodes, intestinal gel infusion, and continuous subcutaneous foslevodopa/foscarbidopa. Different products are not milligram-for-milligram interchangeable and require deliberate conversion and follow-up.¹²¹³

New 2026 safety update: Current U.S. labeling warns that carbidopa/levodopa therapy can reduce vitamin B6 levels and that severe deficiency has been associated with seizures. Clinicians should evaluate vitamin B6 before treatment, periodically during treatment, and when clinically indicated, and supplement low levels according to standard care. Patients should not stop levodopa abruptly or begin high-dose supplements without medical guidance.¹⁵

Other Medication Classes

• Dopamine agonists such as pramipexole, ropinirole, rotigotine, and apomorphine can improve motor symptoms or off time. Risks include sleep attacks, hallucinations, edema, orthostatic hypotension, and impulse-control disorders such as compulsive gambling, shopping, eating, or sexual behavior.
• MAO-B inhibitors such as rasagiline, selegiline, and safinamide provide modest symptomatic benefit and can reduce off time in selected patients.
• COMT inhibitors such as entacapone and opicapone prolong the effect of levodopa and can reduce wearing off, but may increase dyskinesia and other dopaminergic adverse effects.
• Amantadine can reduce dyskinesia and may help some motor symptoms. Confusion, hallucinations, leg edema, skin mottling, and renal dosing are important considerations.
• Istradefylline is an adenosine A2A antagonist used as an add-on to levodopa for off episodes.
• Anticholinergic drugs are now used sparingly, mainly for selected younger patients with troublesome tremor, because they can worsen cognition, constipation, urinary retention, dry mouth, and vision.

Managing Wearing Off and Dyskinesia

A practical evaluation asks whether the problem is delayed onset, early wearing off, unpredictable off time, peak-dose dyskinesia, diphasic dyskinesia, painful off dystonia, or symptoms that do not respond to dopamine. Management may involve changing dose size or timing, addressing protein-related absorption, treating constipation, switching formulation, adding an adjunctive drug, using a rescue treatment, or considering continuous delivery or device therapy.

Increasing dopaminergic treatment may improve off time but worsen dyskinesia, hallucinations, blood-pressure symptoms, or sleepiness. The target is not simply the highest possible “on” time; it is useful on time with acceptable adverse effects and function.

Continuous and Rescue Therapies

• Vyalev: a 24-hour continuous subcutaneous infusion of foscarbidopa/foslevodopa for motor fluctuations in adults with advanced PD. Infusion-site reactions and infections are common practical concerns, and pump setup, dose conversion, skin care, and backup plans require training.¹³
• Onapgo: continuous subcutaneous apomorphine infusion for motor fluctuations in adults with advanced PD. It can cause nausea, hypotension, sleepiness, dyskinesia, hallucinations, and infusion-site problems. Concomitant use with 5-HT3 antagonists such as ondansetron is contraindicated because profound hypotension and loss of consciousness have occurred.¹⁴
• On-demand options: inhaled levodopa or intermittent apomorphine injection can shorten selected off episodes but do not replace the baseline regimen.
• Duopa: intestinal carbidopa/levodopa gel delivered through a tube and pump can provide continuous daytime therapy but requires a procedural access system and device care.

---

Advanced and Device-Based Therapies

Deep Brain Stimulation

DBS places electrodes in targets such as the subthalamic nucleus or globus pallidus internus. The best candidates generally have a clear levodopa response but disabling fluctuations, dyskinesia, or medication-refractory tremor that cannot be managed adequately with medication. Cognitive impairment, uncontrolled psychiatric illness, major surgical risk, and symptoms unlikely to respond to DBS can limit candidacy.

The FDA-approved adaptive feature for compatible Medtronic systems uses sensed neural activity to adjust stimulation automatically within programmed boundaries. It is an evolution of established DBS rather than a separate incisionless treatment. The approved PD indication remains adjunctive bilateral GPi or STN stimulation for levodopa-responsive PD of at least four years’ duration that is not adequately controlled with medication.¹⁶

MR-Guided Focused Ultrasound

Focused ultrasound directs energy through the skull under MRI guidance to create a small permanent thermal lesion. The 2025 FDA expansion covers unilateral pallidothalamic tractotomy for advanced idiopathic PD with medication-refractory moderate-to-severe motor complications, with staged treatment of the previously untreated opposite side no sooner than six months later in selected patients. Patients must be at least 30 years old under the labeled indication.¹⁷

“Incisionless” does not mean noninvasive or risk-free. Unlike DBS, the lesion cannot be turned off, reprogrammed, or removed. Selection should compare the patient’s dominant symptoms, cognitive and gait status, MRI and skull characteristics, surgical risk, goals, and willingness to accept irreversible treatment.

---

Exercise and Rehabilitation: Core Treatment, Not an Add-On

Exercise and rehabilitation improve mobility, balance, gait, strength, endurance, and quality of life. Exercise should be prescribed with the same seriousness as medication, while recognizing that no exercise program has yet been proven to stop the underlying neurodegenerative process.¹⁸

• Aerobic exercise: walking, cycling, swimming, dancing, or other sustained activity adjusted for fitness and fall risk
• Resistance training: progressive strengthening for major muscle groups
• Balance and agility work: turning, stepping, dual-task practice, tai chi, or supervised balance training
• Gait training: cueing, treadmill work, amplitude training, and strategies for freezing
• Physical therapy: individualized treatment for gait, posture, pain, transfers, assistive devices, and fall prevention
• Occupational therapy: home safety, work, driving, energy conservation, handwriting, dressing, and daily tasks
• Speech-language therapy: voice, communication, cough strength, and swallowing assessment or therapy

The program should account for orthostatic hypotension, heart or lung disease, osteoporosis, neuropathy, cognition, freezing, and fall history. Boxing-based classes and other group programs can be motivating, but no branded program is uniquely required, and activities involving impact or rapid direction changes may be unsafe for some patients.

---

Treating Non-Motor Symptoms

Non-motor symptoms often determine quality of life and require direct assessment rather than assuming that more levodopa will solve them.¹⁹

• Orthostatic hypotension: review blood-pressure and PD medications, hydration, salt intake when medically appropriate, compression garments, meal effects, and medications such as midodrine, droxidopa, or fludrocortisone when needed. Supine hypertension must also be considered.
• Constipation: hydration, fiber when appropriate, physical activity, and an individualized bowel regimen. Severe or new symptoms require evaluation for other gastrointestinal disease.
• Sleep: evaluate insomnia, sleep apnea, REM sleep behavior disorder, restless legs symptoms, nocturnal off periods, and medication-related sleepiness. Dream-enactment safety measures are important; melatonin or clonazepam may be considered after individualized review.
• Depression and anxiety: psychotherapy, social support, exercise, and medication when indicated. Anxiety can also fluctuate with levodopa off periods.
• Cognition: review hearing, vision, sleep, mood, anticholinergic burden, infection, and metabolic contributors. Rivastigmine is FDA approved for dementia associated with PD.
• Hallucinations and delusions: first evaluate delirium, infection, dehydration, vision impairment, sleep disruption, and medication effects. Pimavanserin is FDA approved for hallucinations and delusions associated with PD psychosis; it carries the antipsychotic class boxed warning concerning mortality in elderly patients with dementia-related psychosis and is not approved for dementia-related psychosis unrelated to PD psychosis.²⁰
• Swallowing and drooling: speech-language evaluation, aspiration-risk management, dental care, and targeted treatment. New choking, recurrent pneumonia, or unexplained weight loss should not be ignored.

---

Hospital, Emergency, and Medication Safety

Medication timing matters. In the hospital, the medication list should reproduce the patient’s exact home formulation, dose, and schedule rather than default hospital administration times. Delayed or omitted doses can cause severe immobility, aspiration risk, delirium, pain, and prolonged hospitalization. Dopaminergic medications should not be stopped abruptly unless a specialist directs an alternative plan.²¹

Common hospital drugs can worsen parkinsonism. Dopamine-receptor blockers such as metoclopramide, prochlorperazine, promethazine, droperidol, and haloperidol are generally avoided when safer alternatives exist. Medication choice for nausea, agitation, or psychosis should be coordinated with the treating team. For patients using apomorphine, ondansetron and other 5-HT3 antagonists are contraindicated because profound hypotension and loss of consciousness have been reported.¹⁴²¹

Hospital care should also include early mobilization, fall precautions, delirium prevention, constipation management, swallowing screening when indicated, and a plan for medication delivery when the patient cannot swallow. A current medication list and Parkinson’s safety card can prevent avoidable errors.

Seek Urgent or Emergency Evaluation For

• Sudden weakness, numbness, facial droop, speech change, vision loss, severe new imbalance, or another possible stroke symptom
• Fever, severe generalized rigidity, confusion, reduced consciousness, or autonomic instability after abrupt interruption of dopaminergic medication
• Repeated choking, suspected aspiration, inability to swallow medication or fluids, or acute shortness of breath
• Fainting, chest pain, serious injury, or a fall with head trauma
• Rapid new confusion, hallucinations, agitation, or marked decline, especially with fever or urinary, respiratory, or other infection symptoms
• New suicidal thoughts, dangerous impulsive behavior, or inability to maintain safety at home

---

Research: What Is Promising and What Is Not Yet Proven

Tavapadon

Tavapadon is an oral once-daily selective dopamine D1/D5 partial agonist. In the 529-participant TEMPO-1 Phase 3 trial, both tested doses improved the combined MDS-UPDRS Parts II and III score at 26 weeks compared with placebo; common adverse events included nausea, headache, and dizziness. In the 507-participant TEMPO-3 trial, adjunctive tavapadon increased daily on time without troublesome dyskinesia in levodopa-treated patients with motor fluctuations; nausea, dyskinesia, dizziness, orthostatic hypotension, visual hallucinations, and somnolence were among reported adverse events.²³²⁴

These are meaningful symptomatic efficacy findings, not evidence that tavapadon slows neurodegeneration. The FDA application was submitted in 2025; tavapadon remains investigational and has not been approved or become commercially available.²²²⁵

GLP-1 Receptor Agonists

The Phase 2 lixisenatide trial found less worsening of an off-medication motor score at 12 months than placebo, but gastrointestinal adverse effects were common and larger, longer studies are needed before concluding that the drug changes disease progression.²⁶

A large exenatide Phase 3 report originally found no disease-modifying benefit. In June 2026, however, The Lancet issued an Expression of Concern after being informed of findings from a regulatory inspection at one study site. The report should therefore not be treated as a definitive resolution of the GLP-1 question while the concerns are evaluated.²⁷

GLP-1 drugs should not be prescribed for Parkinson’s disease outside an appropriate clinical indication or trial simply because they are used for diabetes or weight management.

α-Synuclein, Genetic, and Other Disease-Modifying Strategies

Antibodies, vaccines, small molecules, gene-targeted approaches, lysosomal therapies, and drugs aimed at LRRK2 or GBA1 pathways are under study. Positive biomarker changes or subgroup signals are hypothesis-generating unless a randomized trial demonstrates meaningful clinical benefit. No α-synuclein-targeted or genetically targeted treatment has yet been proven to slow routine clinical PD.

Cell-Replacement Therapy

Cell therapy aims to replace lost dopamine-producing neurons rather than directly stopping the underlying disease. In the 2025 bemdaneprocel Phase 1 trial, 12 participants underwent bilateral putaminal transplantation and one year of immunosuppression. Imaging supported graft survival, and exploratory motor outcomes were encouraging, but the open-label study had no placebo group and was designed primarily for safety.²⁸

The STEM-PD Phase 1/2 report published July 9, 2026 included eight participants who underwent bilateral transplantation and planned 12 months of immunosuppression. Seven completed 12-month follow-up. One participant developed disseminated pulmonary aspergillosis with central nervous-system involvement while receiving tacrolimus, azathioprine, and corticosteroids and died 10 weeks after transplantation. Investigators did not attribute serious adverse events to the cell product, reported no graft-induced dyskinesia, and found no MRI evidence of tumor formation at 12 months. The trial remains a very small, open-label, single-arm safety study; it cannot establish clinical efficacy.²⁹

Cell replacement is therefore investigational. It involves stereotactic brain surgery, uncertain long-term durability, potential graft-related complications, and—for allogeneic products—the risks of immunosuppression.

---

Conditions That Can Look Like Parkinson’s Disease

• Essential tremor: usually most evident with action or posture, though rest tremor and mixed patterns can occur.
• Drug-induced parkinsonism: associated with dopamine-blocking antipsychotics, anti-nausea drugs, and some other medications; it can be asymmetric and may unmask underlying degenerative disease.
• Progressive supranuclear palsy: early falls, axial rigidity, eye-movement abnormalities, speech or swallowing difficulty, and frontal cognitive or behavioral change.
• Multiple system atrophy: prominent autonomic failure, urinary dysfunction, orthostatic hypotension, cerebellar signs, or poor levodopa response.
• Corticobasal syndrome: markedly asymmetric cortical and movement findings, apraxia, dystonia, myoclonus, or alien-limb phenomena.
• Dementia with Lewy bodies: dementia, fluctuations, visual hallucinations, REM sleep behavior disorder, and parkinsonism; the timing of cognitive and motor symptoms helps distinguish the clinical labels.
• Vascular parkinsonism, normal-pressure hydrocephalus, structural brain disease, and functional movement disorder.

The presence of tremor or a positive DaTscan does not settle the differential diagnosis. Longitudinal follow-up is sometimes the most informative diagnostic tool.

Parkinson’s Tremor and Essential Tremor: Typical Patterns

These are tendencies, not rules. Action tremor occurs in PD, rest tremor can occur in essential tremor, and both conditions can coexist. Diagnosis depends on the complete neurological examination rather than a single tremor feature.

---

Living With Parkinson’s Disease

• Keep an accurate medication list that includes exact formulations and times.
• Track falls, freezing, off periods, dyskinesia, hallucinations, sleepiness, blood-pressure symptoms, and swallowing changes.
• Exercise consistently and revisit physical, occupational, and speech therapy before a crisis develops.
• Address driving, work, home safety, bone health, nutrition, and caregiver strain proactively.
• Review medications regularly for anticholinergic burden, sedation, hypotension, constipation, and dopamine blockade.
• Discuss advance care planning while the patient can fully express preferences; planning does not mean giving up treatment.

What Patients and Families Should Know

1. Parkinson’s is more than tremor. Slowness and stiffness are central, and non-motor symptoms may have the greatest impact.
2. A biomarker is one part of the diagnosis. CSF SAA and skin biopsy can demonstrate synuclein biology, but they do not replace the clinical evaluation or automatically identify the exact synucleinopathy.
3. Medication timing is part of safety. Bring the exact home schedule to every emergency, hospital, and surgical encounter.
4. Exercise and rehabilitation should begin early. Waiting for falls, freezing, or deconditioning makes recovery harder.
5. Advanced therapy should be discussed before function deteriorates too far. DBS, focused ultrasound, and infusion therapies help selected symptoms in selected patients; none is a cure.
6. Research headlines require context. A positive biomarker, small open-label study, or successful Phase 3 symptomatic trial does not necessarily mean disease modification or FDA approval.

---

The Best Parkinson’s Care in 2026 Is Individualized

A modern plan confirms the clinical syndrome; evaluates mimics and red flags; treats the motor symptoms that impair function; identifies non-motor symptoms; builds a sustainable exercise and rehabilitation program; monitors medication adverse effects and interactions; and considers DBS, focused ultrasound, or continuous infusion when fluctuations, dyskinesia, or tremor remain disabling.

Bottom line: Parkinson’s disease remains a clinical diagnosis and a progressive condition without a proven disease-slowing treatment. The 2026 advances are real—better biological markers, new levodopa and apomorphine delivery systems, adaptive DBS, expanded focused-ultrasound labeling, and encouraging investigational therapies—but each has important limits. The best outcomes come from precise diagnosis, timely symptom treatment, exercise, rehabilitation, hospital safety, and repeated adjustment as needs change.

At Los Altos Neurology, we provide individualized evaluation and management of Parkinson’s disease and related movement disorders, including diagnostic clarification, medication optimization, non-motor symptom treatment, rehabilitation planning, interpretation of biomarker testing when appropriate, and guidance regarding advanced therapies.

---

Tremor that doesn’t fit the Parkinson’s pattern? See our essential tremor guide. And when thinking changes accompany Parkinson’s, our memory & cognitive pathway evaluates that dimension directly.

References

1. Tanner CM, Ostrem JL. Parkinson’s Disease. N Engl J Med. 2024;391(5):442-452. doi:10.1056/NEJMra2401857.
2. Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015;30(12):1591-1601. doi:10.1002/mds.26424.
3. Tolosa E, et al. Towards biomarker-based diagnosis of Parkinson disease. Nat Rev Neurol. 2026;22(3):139-151. doi:10.1038/s41582-026-01185-z.
4. Siderowf A, Concha-Marambio L, Lafontant DE, et al. Assessment of heterogeneity among participants in the Parkinson’s Progression Markers Initiative cohort using α-synuclein seed amplification: a cross-sectional study. Lancet Neurol. 2023;22(5):407-417. doi:10.1016/S1474-4422(23)00109-6.
5. Gibbons CH, Levine T, Adler C, et al. Skin Biopsy Detection of Phosphorylated α-Synuclein in Patients With Synucleinopathies. JAMA. 2024;331(15):1298-1306. doi:10.1001/jama.2024.0792.
6. U.S. Food and Drug Administration. Letter of Support: α-Synuclein Seed Amplification Assay as a Clinical-Trial Enrichment Biomarker. 2024.
7. Simuni T, Chahine LM, Poston K, et al. A biological definition of neuronal α-synuclein disease: towards an integrated staging system for research. Lancet Neurol. 2024;23(2):178-190. doi:10.1016/S1474-4422(23)00405-2.
8. Höglinger GU, Adler CH, Berg D, et al. A biological classification of Parkinson’s disease: the SynNeurGe research diagnostic criteria. Lancet Neurol. 2024;23(2):191-204. doi:10.1016/S1474-4422(23)00404-0.
9. Horsager J, Borghammer P. Brain-first vs. body-first Parkinson’s disease: An update on recent evidence. Parkinsonism Relat Disord. 2024;122:106101. doi:10.1016/j.parkreldis.2024.106101.
10. U.S. Food and Drug Administration. DATSCAN (ioflupane I 123 injection) Prescribing Information. 2026.
11. Pringsheim T, Day GS, Smith DB, et al. Dopaminergic Therapy for Motor Symptoms in Early Parkinson Disease: Practice Guideline Summary. Neurology. 2021;97(20):942-957. doi:10.1212/WNL.0000000000012868.
12. U.S. Food and Drug Administration. CREXONT (carbidopa and levodopa) extended-release capsules Prescribing Information. 2026.
13. U.S. Food and Drug Administration. VYALEV (foscarbidopa and foslevodopa) Prescribing Information. 2026.
14. U.S. Food and Drug Administration. ONAPGO (apomorphine hydrochloride) Prescribing Information. 2026.
15. U.S. Food and Drug Administration. FDA Is Requiring Warning about Vitamin B6 Deficiency and Associated Seizures for Drug Products Containing Carbidopa/Levodopa. March 20, 2026.
16. U.S. Food and Drug Administration. Activa, Percept, and SenSight Deep Brain Stimulation Therapy System: Adaptive DBS Summary of Safety and Effectiveness Data (P960009/S478). 2025.
17. U.S. Food and Drug Administration. Exablate Neuro Staged Contralateral Pallidothalamic Tractotomy: Summary of Safety and Effectiveness Data (P150038/S037). 2025.
18. Osborne JA, Botkin R, Colon-Semenza C, et al. Physical Therapist Management of Parkinson Disease: A Clinical Practice Guideline From the American Physical Therapy Association. Phys Ther. 2022;102(4):pzab302. doi:10.1093/ptj/pzab302.
19. Seppi K, Ray Chaudhuri K, Coelho M, et al. Update on treatments for nonmotor symptoms of Parkinson’s disease—an evidence-based medicine review. Mov Disord. 2019;34(2):180-198. doi:10.1002/mds.27602.
20. U.S. Food and Drug Administration. NUPLAZID (pimavanserin) Prescribing Information. 2026.
21. Parkinson’s Foundation. Parkinson’s Foundation Hospital Care Recommendations. Accessed July 10, 2026.
22. AbbVie Inc. AbbVie Submits New Drug Application to U.S. FDA for Tavapadon for the Treatment of Parkinson’s Disease. September 26, 2025. Sponsor news release.
23. Pahwa R, Moro E, Espay AJ, et al. Fixed-Dose Tavapadon for Early Parkinson Disease: The TEMPO-1 Randomized Clinical Trial. JAMA Neurol. 2026;83(5):452-460.
24. Fernandez HH, Isaacson SH, Hauser RA, et al. Tavapadon as Adjunctive Treatment for Parkinson Disease: The TEMPO-3 Randomized Clinical Trial. JAMA Neurol. 2026;83(5):442-451. doi:10.1001/jamaneurol.2026.0577.
25. U.S. Food and Drug Administration. Novel Drug Approvals for 2026. Accessed July 10, 2026.
26. Meissner WG, Remy P, Giordana C, et al. Trial of Lixisenatide in Early Parkinson’s Disease. N Engl J Med. 2024;390:1176-1185. doi:10.1056/NEJMoa2312323.
27. The Lancet Editors. Expression of Concern: Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson’s disease in the UK. Lancet. June 22, 2026.
28. Tabar V, et al. Phase I trial of human embryonic stem cell-derived dopaminergic neurons for Parkinson’s disease. Nature. 2025;641:978-987. doi:10.1038/s41586-025-08845-y.
29. Paul G, Bjartmarz H, Kirkeby A, et al. Human embryonic stem cell-derived dopaminergic cells for Parkinson’s disease: a Phase 1/2 open-label trial. Nat Med. Published online July 9, 2026. doi:10.1038/s41591-026-04525-0.

Medical disclaimer. This article is provided for general educational and informational purposes only. It does not constitute individualized medical advice, diagnosis, treatment, a recommendation for any specific test or therapy, or informed consent. Medical information changes over time, and this article may not reflect developments occurring after its stated review date or apply to your individual circumstances. Do not disregard or delay professional medical advice, or start, stop, or change any medication or treatment, based on this article. Discuss personal medical decisions with a qualified healthcare professional who can evaluate your individual history and circumstances. Accessing or using this website does not, by itself, create a physician–patient relationship with Los Altos Neurology or any of its clinicians. Do not use this website for urgent or emergency medical concerns; call 911 or seek immediate emergency care. Although Los Altos Neurology makes reasonable efforts to provide accurate and current information, it does not guarantee that all content is complete, current, or applicable to every individual. See our full Medical Disclaimer.