This is a single-center, prospective, randomized, open-label, blinded outcome assessment (PROBE) study. At the end of the PROBE study, patients who have completed the study may opt to enter the open-label extension (OLE) study. The objective of the study is to evaluate the safety, tolerability and potential preliminary efficacy of ALT001 in the treatment of patients with multiple system atrophy-cerebellar type (MSA-C).

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by a blend of autonomic dysfunction, Parkinson's syndrome, and cerebellar syndrome. The incidence of MSA ranges from 1.9 to 4.9 per 100,000 individuals, with an average age of onset of 56.2 years. Among individuals aged 50 years and older, the prevalence stands at 3.0 per 100,000. The mean age of MSA onset is 56.2 years, and the median survival ranges from 6.2 to 7.5 years. The MSA-C subtype is associated with a poorer prognosis due to its predominant involvement of the cerebellum and brainstem. In patients with MSA-C, gait and balance disturbances manifest early, leading to nearly 50% of patients requiring a walking aid or physical assistance for ambulation within three years of motor symptom onset. Within five years, 60% of patients become wheelchair-dependent, and after six to eight years, most are completely bedridden, severely impacting their quality of life. Treating MSA-C, a rare neurodegenerative condition, remains a significant challenge. Current symptomatic and supportive therapies fall short of meeting the treatment requirements of MSA-C patients. Furthermore, potential adverse effects and disease progression factors restrict the use of certain drugs, highlighting the critical need for the development of disease-modifying or neuroprotective agents to decelerate disease advancement. "ALT001, a nerve repair protein created by Darwin Origin (Hubei) Biopharmaceutical Co.LTD, is derived from cellular exosomes, a set of specific microenvironmental protein polymers secreted by stem cells under emergency conditions. It boasts selective assembly, targeted delivery, highly efficient tissue repair, exceptional safety, chemical stability, and convenient storage. Previous basic research has indicated ALT001's potential for promoting endogenous neural tissue repair, exhibiting significant neuroprotective and neurorestorative effects in animal models. Therefore, building upon the ongoing study in patients with the MSA-parkinsonian subtype, this project further initiates a single-center, prospective, randomized, open-label, blinded endpoint evaluation (PROBE) study, followed by an open-label extension (OLE) study, specifically targeting patients with the MSA-C subtype. The objectives are to evaluate the safety, tolerability, and potential preliminary efficacy of ALT001 in treating MSA-C patients. This study aims to recruit 20 MSA-C subtype patients aged between 30 and 75 years. The visit content at each stage of this study includes vital signs, neurological examination, laboratory tests (such as routine blood test, blood biochemical examination, coagulation test, etc.), imaging examinations (such as MRI, bladder ultrasound), neurological assessments (such as unified multiple system atrophy rating scale [UMSARS], composite autonomic symptom score [COMPASS], scale for the assessment and rating of ataxia[SARA], quick MSA quality of life questionnaire [MSA-QoL], mini-mental state examination [MMSE]), and cerebrospinal fluid collection. Different stages of the study focus on monitoring patients' concomitant medications, adverse events, and serious adverse events. Detailed follow-up is conducted at the end of each treatment period, with face-to-face visits at specific time points. Additionally, researchers are required to promptly report and manage events when patients develop new neurological symptoms or suspicious events. The follow-up content of the study includes treatment and follow-up assessments at multiple stages. Initially, comprehensive physical examinations, laboratory tests (including blood, urine tests, etc.), multidimensional scoring assessments (such as UMSARS, COMPASS, SARA, MSA-QoL), and brain examinations through imaging techniques such as 3T MRI are performed on subjects at baseline. Subsequently, subjects enter three treatment periods and follow-up stages lasting a total of 90 days, with daily monitoring of vital signs, cerebrospinal fluid collection, laboratory tests, and adverse event documentation in each stage. Follow-up during the Open-Label Extension (OLE) phase (from day 90 to day 165 post-randomization) continues monitoring of vital signs, laboratory tests, and adverse event recording. At the follow-up visits on day 90, day 180, and day 360, comprehensive physical examinations, laboratory tests, gait analysis, bladder ultrasound, MRI, and repeat UMSARS, COMPASS, SARA, MSA-QoL scoring are conducted. Additionally, if patients experience new neurological symptoms or suspicious events, additional visits will be carried out, and researchers are required to submit and interpret relevant data within 72 hours of the event occurrence.The protocol of this study has been approved by the Ethics Committee of Beijing Tiantan Hospital. All participants will provide written informed consents before entering the study.

Inclusion Criteria:

• 1. Age between 30 and 75 years inclusive, either sex;
• 2. Clinically established or clinically probable MSA-C as defined by the 2022 MDS diagnostic criteria for multiple system atrophy;
• 3. Duration of MSA-C-related motor symptoms, including ataxia, no longer than 5 years;
• 4. Score ≤ 3 on Item 14 of the Unified Multiple System Atrophy Rating Scale (UMSARS) Part II (motor examination);
• 5. Estimated life expectancy ≥ 1 year as assessed by the investigator;
• 6. Voluntary participation in this study and provision of written informed consent

Exclusion Criteria:

• 1. Presence of other diseases that may cause ataxia at screening (e.g., infectious diseases, immune-mediated diseases, tumors, paraneoplastic conditions, hereditary disorders, trauma, nutritional deficiencies, toxic exposure, or other neurodegenerative diseases);
• 2. Dementia indicated by the Mini-Mental State Examination (MMSE) at enrollment (score ≤17 for illiterate individuals, ≤20 for primary school education, or ≤24 for junior high school or above) or a prior definitive diagnosis of dementia;
• 3. Evidence of other central nervous system pathologies on brain MRI at screening suggesting a diagnosis of neurodegenerative diseases other than MSA; or other significant pathological findings on brain MRI at screening, including but not limited to: cerebral hemorrhage, acute cerebral infarction, aneurysm, vascular malformation, infectious lesions, brain tumors, or other space-occupying lesions (meningiomas or arachnoid cysts with a maximum diameter <1 cm do not require exclusion);
• 4. Presence of immune-mediated diseases that are inadequately controlled or require treatment with biologic agents;
• 5. Known history of allergies to biologic agents, such as proteins or cell-based products;
• 6. Receipt of any vaccination within the past 1 month;
• 7. Patients with a prior definitive diagnosis of malignancy or those currently receiving anti-tumor drug therapy;
• 8. Patients with a prior definitive diagnosis of epilepsy or those currently taking anti-epileptic drugs;
• 9. Presence of lumbar spine diseases or deformities, or other contraindications to lumbar puncture;
• 10. Coagulation abnormalities at enrollment (e.g., platelet count <100 × 10⁹/L; prothrombin time [PT] >3 seconds), a prior diagnosis of coagulation disorders such as hemophilia, or current use of two or more antiplatelet agents;
• 11. Contraindications to MRI (e.g., claustrophobia, implanted cardiac pacemaker, or ferromagnetic metal);
• 12. Concurrent severe hepatic insufficiency, renal insufficiency, or severe cardiac insufficiency (severe hepatic insufficiency defined as ALT ≥1.5 times the upper limit of normal or AST ≥1.5 times the upper limit of normal; severe renal insufficiency defined as serum creatinine [CRE] ≥1.5 times the upper limit of normal or estimated glomerular filtration rate [eGFR] <40 mL/min/1.73 m²; severe cardiac insufficiency defined as NYHA class 3-4), or any significant abnormalities on physical examination, vital signs, laboratory tests, or electrocardiogram that, in the investigator's opinion, require further examination or treatment, or may interfere with the study procedures or safety;
• 13. Active hepatitis B infection (positive for hepatitis B surface antigen, recurrent/persistent ALT elevation, positive serum HBV DNA, or serum HBV DNA >2 × 10⁵ IU/mL);
• 14. Positive for hepatitis C virus antibody or a history of positive test results;
• 15. Positive for HIV or a history of positive test results;
• 16. Patients with a history of alcohol or substance abuse, or alcohol or substance dependence within the past 2 years;
• 17. Diagnosis of psychiatric disorders, severe anxiety, severe depression, or obvious suicidal ideation according to DSM-V diagnostic criteria;
• 18. Patients who are pregnant, lactating, or have the potential to become pregnant, or those planning a pregnancy;
• 19. Current participation in other interventional trials or use of other investigational biologic agents, drugs, or devices, or use of other investigational drugs within the past 1 month or within 5 half-lives of the drug;
• 20. Inability to comply with follow-up assessments due to other reasons;
• 21. Patients deemed by the investigator to be unsuitable for participation in this study.