The Study of Safety and Preliminary Efficacy of ALT001 in Patients With MultIple System Atrophy-Cerebellar Type

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?endpoint Something the study measures to judge its results, such as a symptom score, a blood test or survival. Outcomes are grouped as primary, secondary and sometimes exploratory. 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?concomitant medications Other medicines a participant takes during the study. Some must be reported; some are restricted., adverse events?adverse events Any unwanted medical problem that happens during a study, whether or not it was caused by the treatment. A 'serious' adverse event is one that meets specific criteria, such as causing death, being life-threatening, requiring or prolonging hospital admission, causing significant disability, or another medically important outcome., 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?baseline Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.. 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.