Progressive Supranuclear Palsy (PSP) Treatment Guide

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Progressive Supranuclear Palsy (PSP) Treatment Guide

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Progressive Supranuclear Palsy (PSP) Treatment Guide

Overview

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">Progressive Supranuclear Palsy (PSP) Treatment Guide</th>
</tr>
<tr>
<td class="label">Medication</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Levodopa/Carbidopa</td>
<td>Dopamine precursor</td>
</tr>
<tr>
<td class="label">Amantadine</td>
<td>NMDA antagonist + dopamine release</td>
</tr>
<tr>
<td class="label">Pramipexole</td>
<td>D2/D3 agonist</td>
</tr>
<tr>
<td class="label">Rotigotine</td>
<td>D1/D2 agonist</td>
</tr>
<tr>
<td class="label">Symptom</td>
<td>First-Line Treatment</td>
</tr>
<tr>
<td class="label">Depression</td>
<td>Sertraline 50-200 mg/day</td>
</tr>
<tr>
<td class="label">Apathy</td>
<td>Methylphenidate 5-20 mg/day</td>
</tr>
<tr>
<td class="label">Pseudobulbar affect</td>
<td>Dextromethorphan/quinidine (Nuedexta)</td>
</tr>
<tr>
<td class="label">Anxiety</td>
<td>SSRIs</td>
</tr>
<tr>
<td class="label">Insomnia</td>
<td>Sleep hygiene + melatonin 3-5 mg</td>
</tr>
<tr>
<td class="label">REM sleep behavior disorder</td>
<td>Melatonin 3-12 mg at bedtime</td>
</tr>
<tr>
<td class="label">Agent</td>
<td>Company</td>
</tr>
<tr>
<td class="label">Semorinemab (RO7105685)</td>
<td>Genentech/Roche</td>
</tr>
<tr>
<td class="label">Tilavonemab (ABBV-8E12)</td>
<td>AbbVie</td>
</tr>
<tr>
<td class="label">Bepran

...

Progressive Supranuclear Palsy (PSP) Treatment Guide

Overview

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">Progressive Supranuclear Palsy (PSP) Treatment Guide</th>
</tr>
<tr>
<td class="label">Medication</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Levodopa/Carbidopa</td>
<td>Dopamine precursor</td>
</tr>
<tr>
<td class="label">Amantadine</td>
<td>NMDA antagonist + dopamine release</td>
</tr>
<tr>
<td class="label">Pramipexole</td>
<td>D2/D3 agonist</td>
</tr>
<tr>
<td class="label">Rotigotine</td>
<td>D1/D2 agonist</td>
</tr>
<tr>
<td class="label">Symptom</td>
<td>First-Line Treatment</td>
</tr>
<tr>
<td class="label">Depression</td>
<td>Sertraline 50-200 mg/day</td>
</tr>
<tr>
<td class="label">Apathy</td>
<td>Methylphenidate 5-20 mg/day</td>
</tr>
<tr>
<td class="label">Pseudobulbar affect</td>
<td>Dextromethorphan/quinidine (Nuedexta)</td>
</tr>
<tr>
<td class="label">Anxiety</td>
<td>SSRIs</td>
</tr>
<tr>
<td class="label">Insomnia</td>
<td>Sleep hygiene + melatonin 3-5 mg</td>
</tr>
<tr>
<td class="label">REM sleep behavior disorder</td>
<td>Melatonin 3-12 mg at bedtime</td>
</tr>
<tr>
<td class="label">Agent</td>
<td>Company</td>
</tr>
<tr>
<td class="label">Semorinemab (RO7105685)</td>
<td>Genentech/Roche</td>
</tr>
<tr>
<td class="label">Tilavonemab (ABBV-8E12)</td>
<td>AbbVie</td>
</tr>
<tr>
<td class="label">Bepranemab (UCB0107)</td>
<td>UCB Pharma</td>
</tr>
<tr>
<td class="label">E2814</td>
<td>Eisai</td>
</tr>
<tr>
<td class="label">JNJ-63733657</td>
<td>Janssen</td>
</tr>
<tr>
<td class="label">Intervention</td>
<td>Score</td>
</tr>
<tr>
<td class="label">Senolytics (D+Q)</td>
<td>54/80</td>
</tr>
<tr>
<td class="label">NAD+ Precursors</td>
<td>53/80</td>
</tr>
<tr>
<td class="label">Melatonin</td>
<td>53/80</td>
</tr>
<tr>
<td class="label">Urolithin A</td>
<td>53/80</td>
</tr>
<tr>
<td class="label">Methylene Blue</td>
<td>50/80</td>
</tr>
<tr>
<td class="label">CoQ10</td>
<td>48/80</td>
</tr>
<tr>
<td class="label">Omega-3 DHA/EPA</td>
<td>48/80</td>
</tr>
<tr>
<td class="label">Curcumin</td>
<td>40/80</td>
</tr>
<tr>
<td class="label">Team Member</td>
<td>Role</td>
</tr>
<tr>
<td class="label">Movement disorder neurologist</td>
<td>Diagnosis, pharmacotherapy, clinical trial enrollment</td>
</tr>
<tr>
<td class="label">Physical therapist</td>
<td>Gait, balance, exercise program</td>
</tr>
<tr>
<td class="label">Occupational therapist</td>
<td>ADL adaptation, home safety, assistive devices</td>
</tr>
<tr>
<td class="label">Speech-language pathologist</td>
<td>Voice therapy, swallowing assessment, AAC</td>
</tr>
<tr>
<td class="label">Neuropsychologist</td>
<td>Cognitive assessment, behavioral strategies</td>
</tr>
<tr>
<td class="label">Social worker</td>
<td>Care coordination, financial planning, support resources</td>
</tr>
<tr>
<td class="label">Palliative care specialist</td>
<td>Symptom management, advance directives, end-of-life planning</td>
</tr>
<tr>
<td class="label">Dietitian/nutritionist</td>
<td>Weight monitoring, diet modification, PEG timing</td>
</tr>
<tr>
<td class="label">Domain</td>
<td>Assessment Tool</td>
</tr>
<tr>
<td class="label">Motor</td>
<td>PSP Rating Scale (PSPRS), Timed Up and Go</td>
</tr>
<tr>
<td class="label">Cognitive</td>
<td>MoCA, Frontal Assessment Battery</td>
</tr>
<tr>
<td class="label">Falls</td>
<td>Fall calendar, injurious fall tracking</td>
</tr>
<tr>
<td class="label">Dysphagia</td>
<td>VFSS, weight tracking</td>
</tr>
<tr>
<td class="label">Mood</td>
<td>GDS, NPI</td>
</tr>
<tr>
<td class="label">Quality of life</td>
<td>PSP-QoL, PDQ-39</td>
</tr>
</table>

Progressive Supranuclear Palsy (PSP) is a progressive 4R tauopathy for which no FDA-approved disease-modifying therapies currently exist[@boxer2017]. This page provides a comprehensive treatment guide covering symptomatic pharmacotherapy, emerging disease-modifying approaches, and multidisciplinary management strategies for patients with PSP.

PSP, first described by Steele, Richardson, and Olszewski in 1964, is characterized by the accumulation of abnormal tau protein in the basal ganglia, brainstem, and cerebellar structures[@steele1964]. The classic Richardson's syndrome (PSP-RS) presents with vertical supranuclear gaze palsy, early postural instability with falls, and frontal cognitive dysfunction. Variant phenotypes include PSP-Parkinsonism (PSP-P), PSP with pure akinesia with gait freezing (PSP-PAGF), and corticobasal syndrome (CBS)[@litvan1996].

Treatment of PSP requires a multimodal approach combining:

Symptomatic pharmacotherapy to address motor and non-motor manifestations

Disease-modifying therapies targeting tau pathology (when available)

Evidence-based neuroprotective supplements with mechanistic rationale

Multidisciplinary rehabilitation including physical, occupational, and speech therapy

Supportive care addressing dysphagia, neuropsychiatric symptoms, and quality of life

Pathway / Interaction Diagram

Mermaid diagram (expand to render)

Symptomatic Pharmacotherapy

Dopaminergic Agents

Levodopa remains the first-line pharmacological trial for motor symptoms in PSP, though efficacy is limited compared to Parkinson's disease[@steele1964]. Approximately 20-30% of patients, particularly those with PSP-P phenotype, show modest transient benefit.

Levodopa Trial Protocol: Initiate at 25/100 mg three times daily, titrate to maximum tolerated dose (typically 600-1000 mg/day of levodopa) over 4-6 weeks. Assess response using UPDRS motor scores. If no objective improvement after adequate trial, discontinue to avoid adverse effects.

Amantadine Use: Consider amantadine 100-200 mg twice daily for patients with prominent akinesia, rigidity, or gait freezing[@chen2019]. Side effects include confusion, hallucinations, peripheral edema, and livedo reticularis. Use cautiously in elderly patients.

Botulinum Toxin for Dystonia

Botulinum toxin injections are first-line for focal dystonia symptoms in PSP[@scelzo2003][@parks2021]:

Retrocollis (neck extension dystonia):

Target muscles: splenius capitis, semispinalis capitis, trapezius
Dose: OnabotulinumtoxinA 50-200 units per session
Interval: Every 3-4 months
Evidence: Moderate - significant improvement in neck posture and pain

Blepharospasm (involuntary eye closure):

Target muscles: orbicularis oculi (pre-tarsal and pre-septal)
Dose: OnabotulinumtoxinA 20-50 units per eye
Interval: Every 3-4 months
Evidence: Strong - first-line treatment

Eyelid-opening apraxia:

Approach: Targeted pretarsal orbicularis injections
Dose: Lower doses than blepharospasm (5-15 units)
Often combined with ptosis/crutch glasses

Sialorrhea (excessive drooling):

Target: Parotid and submandibular glands
Dose: OnabotulinumtoxinA 30-50 units per gland
Evidence: Moderate - significant reduction in drooling

Limb dystonia:

EMG-guided targeting of affected muscles
Dose varies by muscle group and severity

Neuropsychiatric Symptom Management

Neuropsychiatric disturbances are common in PSP and significantly impact quality of life[@golbe2014]:

Apathy in PSP: Apathy is particularly common and often undertreated. It may be difficult to distinguish from depression. Methylphenidate requires monitoring for cardiac side effects. Modafinil may be better tolerated in some patients.

Pseudobulbar Affect: The combination of dextromethorphan/quinidine (Nuedexta) is the only FDA-approved treatment for pseudobulbar affect. Quinidine is a CYP2D6 inhibitor - check for drug interactions.

Cognitive Symptom Management

Cognitive impairment, particularly frontal/executive dysfunction, is a core feature of PSP[@lees2012]. Cholinergic deficits in the pedunculopontine nucleus (PPN) and cortical regions contribute to cognitive impairment:

Rivastigmine: Small open-label trials suggest modest gait and attention benefit
Donepezil: Case reports of mild cognitive improvement; may worsen parkinsonism
Memantine: 10-20 mg/day may provide modest benefit via NMDA modulation
Methylphenidate: May improve apathy-related cognitive dysfunction

Visual and Ocular Symptoms

Vertical supranuclear gaze palsy is the hallmark of PSP. Management strategies:

Prism glasses: Base-down prisms to compensate for downgaze palsy during reading
Lubricating eye drops: For exposure keratitis due to incomplete eyelid closure
Eyelid weights: For eyelid-opening apraxia
Speech/occupational therapy: Environmental modifications for visual limitations

Disease-Modifying Therapy Pipeline

Tau-Targeted Immunotherapies

Multiple monoclonal antibodies targeting tau are in clinical development for PSP[@shoeibi2019][@stamelou2021]:

The failure of tilavonemab and semorinemab in PSP trials highlights the challenge of treating an established neurodegenerative process. Future approaches may need to target earlier disease stages or different tau conformations.

Antisense Oligonucleotides (ASOs)

BIIB080 (IONIS-MAPTRx): Anti-MAPT ASO that reduces total tau production; 50-60% CSF tau reduction demonstrated in Phase 1
NIO752: Anti-tau ASO in development by Novartis

ASOs offer the advantage of reducing tau production at the source, potentially preventing the spread of pathology. However, delivery to the CNS requires intrathecal administration.

Tau Aggregation Inhibitors

LMTM (TRx0237): Methylene blue derivative; failed Phase 3 in AD but LUCIDITY trial in bvFTD showed positive signal as monotherapy
Gantenerumab: Anti-Aβ/tau bispecific antibody in development

GSK-3β Inhibitors

The glycogen synthase kinase-3β (GSK-3β) is a key kinase responsible for tau phosphorylation at multiple disease-relevant epitopes[@noble2005]:

Tideglusib: GSK-3β inhibitor; TAUROS trial showed non-significant trend toward slowed progression; dose-limiting hepatotoxicity[@tolosa2014]
Lithium: Natural GSK-3β inhibitor; requires careful monitoring (see Neuroprotective Strategies below)

Autophagy Enhancers

Agents that enhance autophagy-mediated tau clearance:

Rapamycin (sirolimus): mTORC1 inhibitor; intermittent dosing protocols under investigation
Trehalose: Natural disaccharide that enhances autophagy
Valproic acid: HDAC inhibitor with autophagy-enhancing properties

Evidence-Based Neuroprotective Strategies

Tier 1: Highest-Evidence Interventions (Score ≥55/80)

These interventions have the strongest mechanistic rationale and clinical evidence:

Mediterranean/MIND Diet (Score: 64/80)
The highest-ranked intervention combines Mediterranean and DASH dietary patterns, emphasizing:

Leafy greens (≥6 servings/week)
Berries (≥2 servings/week)
Nuts (≥5 servings/week)
Olive oil as primary fat source
Fish (≥1 serving/week)
Whole grains
Limited red meat, sweets, and fried foods

PREDIMED-Plus and Rush MIND studies demonstrate sustained cognitive benefit. For PSP patients with dysphagia, adapt to texture-modified preparations as needed.

Structured Exercise (Score: 62/80)
Physical exercise is the single most impactful non-pharmacological intervention:

150+ minutes/week moderate aerobic activity
2x/week resistance training
Daily balance exercises
Stage-adapted protocols for advanced disease

Evidence supports benefit in gait speed, balance, fall frequency, and quality of life.

Rasagiline (Score: 60/80)
MAO-B inhibitor with potential neuroprotective properties:

Dose: 1 mg/day
Mechanism: Propargylamine moiety activates anti-apoptotic pathways (Bcl-2 upregulation, PKC activation)
Evidence: NNIPPS trial showed suggestive but non-significant trend toward slowed progression
Note: Low tyramine interaction risk at 1 mg/day

Rapamycin (Score: 57/80)
mTORC1 inhibitor that restores autophagy-mediated tau clearance:

Protocol: 5-6 mg once weekly (intermittent dosing)
Monitoring: Lipid panel, CBC, renal function
Evidence: Geroscience longevity data; PEARL trial framework
Contraindications: Active infection, severe liver disease

Alpha-Lipoic Acid (Score: 56/80)
Mitochondrial antioxidant targeting Complex I deficiency:

Dose: R-enantiomer 600 mg/day with meals
Mechanism: Scavenges reactive oxygen species, chelates metals, regenerates other antioxidants
Evidence: Mixed results in clinical trials; strong preclinical data

TUDCA/UDCA (Score: 56/80)
Bile acid chemical chaperones:

Dose: TUDCA 500 mg/day
Mechanism: Reduce endoplasmic reticulum stress, improve mitochondrial function
Evidence: AMX0035 (CENTAUR/PHOENIX trials) provides class evidence for neuroprotection in motor neuron disease

Low-Dose Lithium (Score: 55/80)
GSK-3β inhibitor that directly reduces tau phosphorylation:

Dose: 150-300 mg/day targeting serum levels of 0.3-0.6 mEq/L
Monitoring: Thyroid function, renal function, lithium levels
Contraindications: Thyroid disease, renal impairment, cardiac disease
Evidence: Preclinical strong; clinical mixed[@noble2005]

Spermidine (Score: 55/80)
Natural polyamine that induces autophagy:

Dose: Wheat germ extract 1.2 mg/day spermidine equivalent
Mechanism: EP300 inhibition and TFEB activation
Evidence: SmartAge RCT demonstrated cognitive benefit in older adults

Tier 2: Moderate-Evidence Interventions (Score 45-54/80)

Critical Drug Interactions

Methylene blue + SSRIs: Serotonin syndrome risk — contraindicated
Lithium + NSAIDs: Increased lithium levels — monitor closely
Rapamycin + CYP3A4 inhibitors: Increased rapamycin exposure
Rasagiline + tyramine-rich foods: Hypertensive crisis (low risk at 1 mg/day)
Amantadine + anticholinergics: Increased confusion risk

Non-Pharmacological Interventions

Physical Therapy

Physical therapy is the single most impactful intervention for functional outcomes in PSP:

Gait and Balance Training:

Treadmill walking with body-weight support
Rhythmic auditory cueing for freezing episodes
Tai chi for balance improvement
Standing perturbation training
Dynamic weight shifting exercises

Fall Prevention:

Home safety assessment: grab bars, raised toilet seats, non-slip mats
Hip protectors for high-risk patients
Assistive devices: walkers, canes (adapted for vision impairment)

Neck and Spinal Exercises:

Active and passive range-of-motion for retrocollis
Isometric strengthening of cervical flexors
Postural re-education

Aerobic Conditioning:

Seated cycling for advanced stages
Aquatic therapy to reduce fall risk
Maintain cardiovascular fitness throughout disease course

Occupational Therapy

Adaptive equipment: Weighted utensils, specialized writing aids
Prism glasses: For downward gaze compensation during reading and meals
Energy conservation: Task simplification techniques
Home modification: Lighting, clutter reduction, bathroom safety
Wheelchair/ scooter assessments: For advanced disease

Speech-Language Pathology

Lee Silverman Voice Treatment (LSVT) LOUD: Gold-standard for hypophonia
Swallowing assessment: Videofluoroscopic swallowing study (VFSS)
Diet modification: Based on VFSS findings
Augmentative and alternative communication (AAC): Eye-gaze devices for advanced dysarthria
Swallowing techniques: Supraglottic swallow, effortful swallow

Cognitive Rehabilitation

Cognitive reserve strategies: intellectually stimulating activities, social engagement, music therapy
Compensatory strategies: external memory aids, structured routines
Caregiver training: communication strategies, behavioral management

Dysphagia and Nutrition Management

Dysphagia develops in most PSP patients and is the leading cause of death via aspiration pneumonia[@mller2001]:

Videofluoroscopic swallowing study (VFSS): Baseline assessment at diagnosis, repeated every 6-12 months
Diet modification: Thickened liquids, soft solids as indicated by VFSS
Swallowing techniques: Chin-tuck maneuver, supraglottic swallow technique
PEG tube discussion: Initiate early as part of advance care planning; place before severe cachexia
Weight monitoring: Monthly body mass tracking with nutritional supplementation as needed

Multidisciplinary Care Model

Optimal PSP management requires a coordinated team approach[@golbe2014]:

Biomarkers and Monitoring

Disease Progression Biomarkers

Tracking disease progression in PSP requires multimodal assessment[@respondek2019]:

Neurofilament light chain (NfL): Elevated in CSF and blood; correlates with disease severity and progression rate
Total tau and phosphorylated tau: CSF total tau elevated in PSP vs. controls; p-tau181 shows diagnostic promise
Neurogranin: Synaptic marker elevated in PSP; reflects synaptic degeneration

Clinical Monitoring

Imaging Biomarkers

MRI: Midbrain and superior cerebellar peduncle atrophy; "hummingbird sign" on midsagittal view
PET/SPECT: Dopaminergic dysfunction on FP-CIT SPECT; reduced FDG uptake in frontal cortex and brainstem
Tau PET: Emerging role in differential diagnosis and clinical trial enrollment

Clinical Trials and Future Directions

Active PSP Clinical Trials

The field of PSP therapeutics is actively evolving. Key resources for finding trials:

[ClinicalTrials.gov](https://clinicaltrials.gov/search?cond=Progressive+Supranuclear+Palsy): Search for active PSP trials
[CurePSP](https://www.psp.org/): Patient advocacy organization with trial information

Emerging Approaches

CSF1R inhibitors: Target neuroinflammation via microglial modulation
TREM2 agonists: Enhance microglial phagocytosis of pathological tau
Gene therapy: AAV-based tau siRNA delivery
Combination approaches: Multi-target therapies addressing tau, neuroinflammation, and neurodegeneration simultaneously

Precision Medicine

Future PSP treatment will likely incorporate:

Genetic stratification: MAPT mutations, risk alleles
Biomarker-guided patient selection: Tau PET, CSF biomarkers
Phenotype-specific approaches: Different treatment strategies for PSP-RS vs. PSP-P vs. CBS

Patient Resources and Support

Organizations

[CurePSP](https://www.psp.org/): Primary patient advocacy for PSP, CBS, and related disorders
[The PSP Association (UK)](https://pspassociation.org.uk/): UK-based support organization
[NINDS PSP Information](https://www.ninds.nih.gov/Disorders/All-Disorders/Progressive-Supranuclear-Palsy-Information-Page): NIH resource

Practical Resources

Advance care planning: Early discussion of directives given predictable progression
Driving assessment: Typically discontinued within 1-2 years due to gaze palsy and falls
Caregiver support: Respite services, support groups, financial assistance programs

References

[Boxer AL, et al. Advances in progressive supranuclear palsy. Lancet Neurol. 2017](https://pubmed.ncbi.nlm.nih.gov/28592453/)

[Oertel WH, et al. Therapeutic approaches to PSP. J Neural Transm. 2020](https://pubmed.ncbi.nlm.nih.gov/32890128/)

[Stamelou M, Höglinger GU. Novel therapeutics in PSP. Curr Opin Neurol. 2021](https://pubmed.ncbi.nlm.nih.gov/33938199/)

[Steele JC, et al. Progressive supranuclear palsy. Arch Neurol. 1964](https://pubmed.ncbi.nlm.nih.gov/14138406/)

[Litvan I, et al. Clinical research criteria for PSP. Neurology. 1996](https://pubmed.ncbi.nlm.nih.gov/8577393/)

[Scelzo E, et al. Botulinum toxin in PSP. J Neurol. 2003](https://pubmed.ncbi.nlm.nih.gov/14124695/)

[Lamb R, et al. PSP and CBD treatment options. Curr Treat Options Neurol. 2016](https://pubmed.ncbi.nlm.nih.gov/27629091/)

[Respondek G, et al. Current and future therapeutic approaches to PSP. Expert Rev Neurother. 2019](https://pubmed.ncbi.nlm.nih.gov/31704935/)

[Tolosa E, et al. Tideglusib in PSP. Mov Disord. 2014](https://pubmed.ncbi.nlm.nih.gov/24448240/)

[Höglinger GU, et al. Tilavonemab in PSP. Lancet Neurol. 2021](https://pubmed.ncbi.nlm.nih.gov/34118189/)

[Shoeibi A, et al. Frontrunner in PSP. Front Neurol. 2019](https://pubmed.ncbi.nlm.nih.gov/31643103/)

[Golbe LI. Progressive supranuclear palsy. Semin Neurol. 2014](https://pubmed.ncbi.nlm.nih.gov/24824798/)

[Nath U, et al. Prevalence of PSP in the UK. Brain. 2001](https://pubmed.ncbi.nlm.nih.gov/12117563/)

[Müller J, et al. Dysphagia in parkinsonian disorders. Arch Neurol. 2001](https://pubmed.ncbi.nlm.nih.gov/11585538/)

[Noble W, et al. GSK-3β inhibition and tauopathy. Proc Natl Acad Sci U S A. 2005](https://pubmed.ncbi.nlm.nih.gov/15728835/)

[Kalia LV, Lang AE. Parkinson's disease. Lancet. 2015](https://pubmed.ncbi.nlm.nih.gov/25904084/)

[Fager V, et al. Tau-targeted therapies. Lancet Neurol. 2018](https://pubmed.ncbi.nlm.nih.gov/30047449/)

[Chen L, et al. Amantadine in PSP. Park Relat Disord. 2019](https://pubmed.ncbi.nlm.nih.gov/30658932/)

[Parks A, et al. Botulinum toxin for dystonia. Toxins. 2021](https://pubmed.ncbi.nlm.nih.gov/33467023/)

[Lees AJ, et al. Clinical diagnosis of PSP. Mov Disord. 2012](https://pubmed.ncbi.nlm.nih.gov/22807184/)

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

[TREM2-mediated microglial tau clearance enhancement](/hypothesis/h-b234254c) — <span style="color:#ffd54f;font-weight:600">0.55</span> · Target: TREM2
[TREM2 Conformational Stabilizers for Synaptic Discrimination](/hypothesis/h-044ee057) — <span style="color:#ffd54f;font-weight:600">0.58</span> · Target: TREM2
[Astrocyte-Mediated Neuronal Epigenetic Rescue](/hypothesis/h-8fe389e8) — <span style="color:#81c784;font-weight:600">0.64</span> · Target: HDAC
[TFEB-PGC1α Mitochondrial-Lysosomal Decoupling](/hypothesis/h-e5a1c16b) — <span style="color:#ffd54f;font-weight:600">0.52</span> · Target: TFEB
[The Mitochondrial-Lysosomal Metabolic Coupling Dysfunction](/hypothesis/h-e3e8407c) — <span style="color:#ffd54f;font-weight:600">0.52</span> · Target: TFEB

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Progressive Supranuclear Palsy (PSP) Treatment Guide

Progressive Supranuclear Palsy (PSP) Treatment Guide

Overview

Progressive Supranuclear Palsy (PSP) Treatment Guide

Overview

Pathway / Interaction Diagram

Symptomatic Pharmacotherapy

Dopaminergic Agents

Botulinum Toxin for Dystonia

Neuropsychiatric Symptom Management

Cognitive Symptom Management

Visual and Ocular Symptoms

Disease-Modifying Therapy Pipeline

Tau-Targeted Immunotherapies

Antisense Oligonucleotides (ASOs)

Tau Aggregation Inhibitors

GSK-3β Inhibitors

Autophagy Enhancers

Evidence-Based Neuroprotective Strategies

Tier 1: Highest-Evidence Interventions (Score ≥55/80)

Tier 2: Moderate-Evidence Interventions (Score 45-54/80)

Critical Drug Interactions

Non-Pharmacological Interventions

Physical Therapy

Occupational Therapy

Speech-Language Pathology

Cognitive Rehabilitation

Dysphagia and Nutrition Management

Multidisciplinary Care Model

Biomarkers and Monitoring

Disease Progression Biomarkers

Clinical Monitoring

Imaging Biomarkers

Clinical Trials and Future Directions

Active PSP Clinical Trials

Emerging Approaches

Precision Medicine

Patient Resources and Support

Organizations

Practical Resources

See Also

References

Related Hypotheses

💬 Discussion