MSC-Exosome Therapy for Frontotemporal Dementia

A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Via Intranasal Administration in Patients With Frontotemporal Dementia

This study is testing a new treatment for Frontotemporal Dementia (FTD) - a progressive brain disease that affects personality, behavior, and language. Currently, there is no cure for FTD and no approved medication that can slow down or stop the disease. Existing treatments only help manage some symptoms temporarily.

The investigational treatment in this study is made from exosomes - tiny particles naturally released by umbilical cord stem cells. Exosomes act like "message carriers" between cells. Researchers believe they may help protect brain cells, reduce harmful protein buildup, and improve brain function.

The exosomes will be given as a nasal spray (sprayed into the nose). This method may allow the treatment to reach the brain directly without needing to pass through the blood-brain barrier (a natural protective layer that often blocks medications from entering the brain).

Study Overview

• Status: Not yet recruiting
• Conditions: Frontotemporal Dementia
• Intervention / Treatment: Other: Placebo Comparator (0.9% NaCl); Biological: Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes （Low-Dose）; Biological: Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes （High-Dose）

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Chao Gao, MD，Ph.D; Phone Number: +8618217590273; Email: anshangaochao@163.com
• Study Contact Backup: Name: Shengdi Chen, MD, Ph.D; Phone Number: +8613818018166; Email: chensd@rjh.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of probable frontotemporal dementia (FTD), including behavioral variant (bvFTD), semantic variant primary progressive aphasia (svPPA), or non-fluent variant primary progressive aphasia (nfvPPA), according to established diagnostic criteria, with supportive neuroimaging evidence showing frontal and/or temporal lobe atrophy score of 2 or higher on brain CT or MRI.
2. Age between 30 and 80 years (inclusive) at screening.
3. Study partner who agrees to participate in the study, provides at least 3 hours of daily care or visits, and can manage all study medication.
4. Frontotemporal Lobar Degeneration Clinical Dementia Rating (FTLD-CDR) score of 0-2 and Mini-Mental State Examination (MMSE) score greater than 10 at screening.
5. Stable use of cognition- or behavior-related medications (e.g., cholinesterase inhibitors, memantine, antidepressants, antipsychotics, mood stabilizers, benzodiazepines) for at least 30 days before baseline.
6. Signed informed consent form.

Exclusion Criteria:

1. History of stroke or other neurological or psychiatric disorder (other than FTD) that is considered the primary cause of behavioral symptoms.
2. Pregnancy or breastfeeding, or plan to become pregnant during the study period.
3. Use of any investigational or experimental drug or device within 60 days or 5 half-lives (whichever is longer) prior to screening.
4. Presence of speech or language impairment that severely affects the implementation of neuropsychological assessments or safety evaluations per the study protocol.
5. History of cancer, unless: (a) considered cured; (b) not actively receiving anti-cancer therapy or radiation and the investigator judges that treatment is unlikely to be needed in the next 5 years; or (c) for prostate cancer or basal cell carcinoma, no significant progression in the past 2 years.
6. Any clinically significant hematologic, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disease that would interfere with study participation. Participants may be included if the condition has been stable for at least one year and the investigator judges that it does not affect participation.
7. Known hypersensitivity to the study drug or any of its excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Comparator; Participants randomized to the placebo group will receive intranasal spray of normal saline (0.9% sodium chloride), 1 mL per administration, twice weekly for 24 consecutive weeks. The placebo is identical in appearance, packaging, and administration procedure to the active investigational product to maintain blinding.	Other: Placebo Comparator (0.9% NaCl); Participants randomized to the placebo group will receive intranasal spray of normal saline (0.9% sodium chloride), 1 mL per administration, twice weekly for 24 consecutive weeks. The placebo is identical in appearance, packaging, and administration procedure to the active investigational product to maintain blinding.
Experimental: Low-Dose Exosome Group; Participants randomized to the low-dose group will receive intranasal spray of human umbilical cord mesenchymal stem cell-derived exosomes (MSC-Exos), 1 mL per administration containing 24 × 10⁹ particles, twice weekly for 24 consecutive weeks.	Biological: Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes （Low-Dose）; Participants randomized to the low-dose group will receive intranasal spray of human umbilical cord mesenchymal stem cell-derived exosomes (MSC-Exos), 1 mL per administration containing 24 × 10⁹ particles, twice weekly for 24 consecutive weeks.
Experimental: High-Dose MSC-Exosome; Participants randomized to the high-dose group will receive intranasal spray of human umbilical cord mesenchymal stem cell-derived exosomes (MSC-Exos), 1 mL per administration containing 24 × 10⁹ particles, three times weekly for 24 consecutive weeks. Enrollment in this arm will only begin after the first 3 participants in the low-dose arm complete the 4-week safety lead-in and 21-day safety observation period without dose-limiting toxicity or serious adverse events.	Biological: Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes （High-Dose）; Participants randomized to the high-dose group will receive intranasal spray of human umbilical cord mesenchymal stem cell-derived exosomes (MSC-Exos), 1 mL per administration containing 24 × 10⁹ particles, three times weekly (e.g., Monday, Wednesday, Friday) for 24 consecutive weeks. Enrollment in this arm will only begin after the first 3 participants in the low-dose arm complete the 4-week safety lead-in and 21-day safety observation period without dose-limiting toxicity or serious adverse events.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Efficacy: Change in CDR plus NACC FTLD Score	Change from baseline in the Clinical Dementia Rating (CDR®) Dementia Staging Instrument plus the National Alzheimer's Coordinating Center Frontotemporal Lobar Degeneration (NACC FTLD) module total score at Week 24. Scale Range: Minimum = 0, Maximum = 30 Interpretation: A higher score indicates worse cognitive and behavioral function; a decrease (negative change) from baseline indicates improvement.	Baseline and Week 24
Safety and Tolerability: Incidence of Adverse Events	Number of participants with treatment-emergent adverse events (AE), serious adverse events (SAE), adverse drug reactions (ADR), and serious adverse drug reactions (SADR), including assessment of causality and severity. Adverse events include local nasal reactions (e.g., epistaxis, nasal congestion, rhinorrhea, cough, pharyngeal discomfort, sneezing, nasal dryness) and systemic reactions (e.g., rash, pruritus, facial/eyelid swelling, dyspnea, chest tightness, fever, chills). Severity graded as mild, moderate, or severe.	Baseline through Week 24 (end of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Global Cognition: MMSE Score	Change from baseline in Mini-Mental State Examination (MMSE) total score. Range: 0-30, with higher scores indicating better cognitive function.	Baseline, Week 12, Week 24
Change in Global Cognition: MoCA Score	Change from baseline in Montreal Cognitive Assessment (MoCA) Basic Version total score. Range: 0-30, with higher scores indicating better cognitive function.	Baseline, Week 12, Week 24
Change in Language Function: BNT Score	Change from baseline in Boston Naming Test (BNT) total score, measuring confrontation naming ability. Unabbreviated Scale Title: Boston Naming Test (BNT) Scale Range: Minimum = 0, Maximum = 60 Interpretation: Higher scores indicate better language function; an increase (positive change) from baseline indicates improvement.	Baseline, Week 12, Week 24
Change in Language Function: Semantic Fluency Test	Change from baseline in the number of animals named per minute on the Semantic Fluency Test, measuring verbal fluency and lexical access. Unabbreviated Scale Title: Semantic Fluency Test (Animal Naming) Scale Range: Minimum = 0, Maximum = no fixed upper limit (typical range in healthy adults: 12-25; in FTD patients: 0-15) *Note: The test is scored as the number of unique, correct animal names produced within 60 seconds. While theoretically open-ended, practical scores rarely exceed 30-40.* Interpretation: Higher scores indicate better verbal fluency and language function; an increase (positive change) from baseline indicates improvement.	Baseline, Week 12, Week 24
Change in Neuropsychiatric Symptoms: NPI Score	Change from baseline in Neuropsychiatric Inventory (NPI) total score, assessing behavioral and psychiatric symptoms in dementia. Unabbreviated Scale Title: Neuropsychiatric Inventory (NPI) Scale Range: Minimum = 0, Maximum = 144 Note: The NPI assesses 12 domains (e.g., delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, motor disturbances, sleep disturbances, appetite changes, and aberrant motor behavior). Each domain is scored as frequency (1-4) × severity (1-3), for a maximum of 12 per domain. Interpretation: Lower scores indicate fewer or less severe neuropsychiatric symptoms; a decrease (negative change) from baseline indicates improvement.	Baseline, Week 12, Week 24
Change in Neuropsychiatric Symptoms: FBI Score	Change from baseline in Frontal Behavior Inventory (FBI) total score, measuring behavioral symptoms associated with frontotemporal dysfunction. Unabbreviated Scale Title: Frontal Behavior Inventory (FBI) Scale Range: Minimum = 0, Maximum = 72 *Note: The FBI assesses 24 items (each scored 0-3), covering negative symptoms (e.g., apathy, indifference, loss of insight) and positive/disinhibited symptoms (e.g., impulsivity, perseveration, irritability, poor judgment).* Interpretation: Lower scores indicate fewer or less severe frontal behavioral symptoms; a decrease (negative change) from baseline indicates improvement.	Baseline, Week 12, Week 24
Change in Executive Function: FAB Score	Change from baseline in Frontal Assessment Battery (FAB) total score, assessing executive functions including conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. Unabbreviated Scale Title: Frontal Assessment Battery (FAB) Scale Range: Minimum = 0, Maximum = 18 Note: The FAB consists of 6 subtests, each scored from 0 to 3. Interpretation: Higher scores indicate better executive function; an increase (positive change) from baseline indicates improvement.	Baseline, Week 12, Week 24
Change in Daily Function and Behavior: ADL Score	Change from baseline in Activities of Daily Living (ADL) scale total score, measuring the participant's ability to perform daily living activities. Unabbreviated Scale Title: Barthel Index of Activities of Daily Living (or specify the actual scale used, e.g., Katz Index of Independence in Activities of Daily Living, Lawton Instrumental Activities of Daily Living Scale) Scale Range (Barthel Index): Minimum = 0, Maximum = 100 Note: The Barthel Index assesses 10 items (e.g., feeding, bathing, grooming, dressing, bowel and bladder control, toilet use, transfers, mobility, stair climbing). Alternative ADL scales may have different ranges (e.g., Katz Index: 0-6). Interpretation: Lower scores indicate worse functional status (greater dependence); higher scores indicate better functional status (greater independence). Please confirm - the provided description states "Lower scores indicate better functional status," which is atypical for most ADL scales. Usually, higher scores = better fun	Baseline, Week 12, Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brain Structure: Regional Brain Volume	Change from baseline in regional brain volume, assessed by structural magnetic resonance imaging (MRI), to evaluate the effect of intranasal exosome treatment on brain structure in FTD patients. Units of Measure: Cubic millimeters (mm³) or percentage change from baseline in specific regions of interest (e.g., frontal lobe, temporal lobe, hippocampus) Interpretation: Specific regional volume changes will be analyzed exploratory. Direction of improvement is not predefined for this exploratory outcome.	Baseline，and Week 24
Change in Brain Function: Resting-State Functional Connectivity	Change from baseline in resting-state functional connectivity, assessed by functional magnetic resonance imaging (fMRI), to evaluate the effect of intranasal exosome treatment on brain function in FTD patients. Units of Measure: Correlation coefficient (z-scored or Fisher-transformed correlation values between predefined brain networks or regions of interest) Interpretation: Changes in functional connectivity will be analyzed exploratory. Direction of improvement is not predefined for this exploratory outcome.	Baseline and Week 24
Change in Plasma Biomarker: Neurofilament Light Chain (NfL)	Exploratory outcome: Change from baseline in plasma levels of neurofilament light chain (NfL), a biomarker of axonal injury associated with frontotemporal dementia pathophysiology. Units of Measure: Picograms per milliliter (pg/mL) Interpretation: Higher levels indicate greater axonal injury; a decrease (negative change) from baseline may suggest improvement (reduced neuronal damage). This is an exploratory outcome.	Baseline，Week 24
Change in Plasma Biomarker: Tau Proteins	Exploratory outcome: Change from baseline in plasma levels of tau proteins (e.g., total tau, phosphorylated tau), biomarkers associated with frontotemporal dementia pathophysiology. Units of Measure: Picograms per milliliter (pg/mL) - please confirm based on assay used Interpretation: Higher levels may indicate greater neurodegeneration; a decrease (negative change) from baseline may suggest improvement. This is an exploratory outcome.	Baseline and Week 24

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Investigators: Principal Investigator: Shengdi Chen, MD, Ph.D, Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: June 2, 2026
• First Submitted That Met QC Criteria: June 6, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 6, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: exosomes; Frontotemporal Dementia
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Metabolic Diseases; Neurocognitive Disorders; Dementia; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Frontotemporal Lobar Degeneration; Nutritional and Metabolic Diseases; Frontotemporal Dementia
• Other Study ID Numbers: 2026-221

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No