SNUG01 Successfully Completed the First Domestic AAV Gene Therapy and Three Months Follow-up of Patients with Gradual Frozen Disease

amyotrophic lateral sclerosis(ALS, also known as progressive freezing disease)is one of the top five terminally ill identified by the World Health Organization. Pathological manifestations of upper motor neurons and lower motor neurons damage, resulting in systemic muscle weakness and atrophy. The common symptom is the procedural loss of muscle control, that is, with the development of the disease, the patient's speech, swallowing, grasping, walking, moving, breathing and other functions are gradually lost. The average survival period from onset to death is 2 to 4 years, and there is still no effective treatment.

Recently, a "single-arm, open-label exploratory clinical study evaluating single intrathecal injection of SNUG01 in patients with amyotrophic lateral sclerosis" was successfully initiated and followed up in parallel with the first 3-month follow-up after compassionate medication (compassionate administration after ethical approval). This is the first clinical trial of AAV gene therapy for amyotrophic lateral sclerosis in China.

SNUG01 is a gene therapy drug with adeno-associated virus (AAV) as the carrier, using Shenji Changhua's exclusive therapeutic target SG001, in order to achieve the therapeutic effect of "one-time administration, long-term effect.SNUG01 in preclinical animal experiments, showing a significant protective effect on neurons.SNUG01 is expected to open a new field of ALS treatment, improve the situation of no cure, and bring new hope to patients and their families..

This study included 1 ALS patient with a disease course of more than 24 months and rapid disease progression in need of treatment. The patient's survival time has entered the countdown and there is a lack of effective drugs for the treatment of ALS at home and abroad. Judging that the social and scientific value of SNUG01 and the potential benefits of the subjects outweighed the risks associated with the intervention, the investigators agreed to grant compassionate gene therapy.

In terms of safety evaluation, this sympathetic administration has completed 28 days of dose-limiting toxicity DLT * observation, and no DLT events have been found. No obvious adverse events have been seen in the subject 3 months after administration. In terms of efficacy evaluation, the patient's disease progression was more stable than before, and there was no significant re-progression overall. Subjective and objective indicators such as EMG results and ALSFRS-R scores showed an improvement trend, and SG001 gene expression increased after administration. To sum up, the overall condition of the subjects is good, but the long-term safety and efficacy still need continuous follow-up observation.

During the follow-up of 3 months after the administration, the clinical expert team of Peking University Third Hospital was invited to visit the subjects in person. Professor He He of the Third Hospital of Peking University said that according to the current situation, the first sympathetic medication of SNUG01 is stable and looks forward to the following observation results. Professor Fan Dongsheng of the Third Hospital of Peking University said that the medication situation of the first subject was stable, and some indicators, especially the key electrophysiological indicators, have been improved to some extent. This study, as the first case of AAV gene therapy for gradual freezing disease in China, is of great significance to explore new treatment methods for gradual freezing disease, and looks forward to the therapeutic effect of SNUG01.

*According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0, if the subject experienced an adverse event of CTCAE grade 3 or higher toxicity that was possibly, likely, or definitely related to the study drug, accompanied by clinical symptoms and that required drug treatment (including any subject death, important clinical laboratory findings, or any severe local complications in the injection area related to the study drug).