1.The Establishment of a Virus-related Lymphoma Risk Warning System and Health Management Model Based on Traditional Chinese Medicine Conditions
Hanjing LI ; Shunan LI ; Zewei ZHUO ; Shunyong WANG ; Qiangqiang ZHENG ; Bingyu HUANG ; Yupeng YANG ; Chenxi QIU ; Ningning CHEN ; He WANG ; Tingbo LIU ; Haiying FU
Journal of Traditional Chinese Medicine 2025;66(4):335-339
Virus-related lymphoma exhibits a dual nature as both a hematologic malignancy and a viral infectious disease, making it more resistant to treatment and associated with poorer prognosis. This paper analyzes the understanding and therapeutic advantages of traditional Chinese medicine (TCM) in virus-related lymphoma. It proposes a TCM-based approach centered around syndrome differentiation, using standardized measurements of the overall TCM condition, multi-omics research of hematologic tumors, and artificial intelligence technologies to identify the "pre-condition" of virus-related lymphoma. A risk warning model will be established to early identify high-risk populations with viral infections that may develop into malignant lymphoma, thereby establishing a risk warning system for virus-related lymphoma. At the same time, a TCM health management approach will be applied to manage and regulate virus-related lymphoma, interrupting its progression and forming a human-centered, comprehensive, continuous health service model. Based on this, a standardized, integrated clinical prevention and treatment decision-making model for virus-related lymphoma, recognized by both Chinese and western medicine, will be established to provide TCM solutions for primary prevention of major malignant tumors.
2.Study on the distribution of traditional Chinese medicine syndromes and syndrome elements in lymphoma and the correlation between syndromes and Western medicine clinical indicators
Hanjing LI ; Shunan LI ; Zewei ZHUO ; Shunyong WANG ; Qiangqiang ZHENG ; Bingyu HUANG ; Yupeng YANG ; Chenxi QIU ; Ningning CHEN ; Yanyan QIU ; He WANG ; Tingbo LIU ; Haiying FU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):127-137
Objective:
To investigate the distribution of traditional Chinese medicine (TCM) syndromes and syndrome elements in lymphoma, as well as the correlation between TCM syndromes and Western clinical indicators, in order to analyze associations between TCM syndromes and these indicators.
Methods:
From January 2023 to May 2024, 216 patients with lymphoma who met the inclusion criteria in the Department of Hematology, Third People′s Hospital Affiliated to Fujian University of Traditional Chinese Medicine were enrolled. Four diagnostic methods were applied to perform TCM syndrome differentiation and extract syndrome elements. The correlations between various syndromes and blood test indicators of lactate dehydrogenase (LDH), β2-microglobulin (β2-MG), immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), white blood cell (WBC), hemoglobin (Hb), platelet count (PLT), neutrophil (NEUT), immunohistochemical markers of B-cell lymphoma-6 (BCL6), B-cell lymphoma-2 (BCL2), proto-oncogene MYC, and Ki67 protein expression, Ann Arbor staging, international prognostic index (IPI) score, bone marrow infiltration, concurrent infections during chemotherapy, and post-chemotherapy bone marrow suppression rate were analyzed.
Results:
Five TCM syndromes, ranked by frequency, were syndromes of yin deficiency with phlegm accumulation(41.67%), qi depression with phlegm obstruction(30.56%), cold-phlegm congelation and stagnation(12.96%), phlegm-blood stasis toxin(12.04%), and lingering pathogen due to deficient vital qi(2.77%). Yin deficiency(50.93%) and phlegm(45.37%) were the more prevalent syndrome elements. The TCM syndromes were correlated with β2-MG, PLT, MYC, BCL2/MYC, Ki67 protein expression, and bone marrow infiltration (P<0.05). No statistically significant differences were observed in Ann Arbor staging or IPI score across the syndromes. Compared to the syndrome of cold-phlegm congelation and stagnation, the syndrome of qi depression with phlegm obstruction exhibited higher levels of NEUT, MYC, BCL2/MYC, and Ki67 protein expression, as well as a higher rate of post-chemotherapy bone marrow suppression (P<0.05); the syndrome of phlegm-blood stasis toxin showed higher MYC and BCL2/MYC protein expression and a higher rate of post-chemotherapy bone marrow suppression rate (P<0.05); the syndrome of yin deficiency with phlegm accumulation demonstrated higher MYC and BCL2/MYC protein expression and bone marrow infiltration rates, whereas PLT level was lower (P<0.05); the syndrome of lingering pathogen due to deficient vital qi had higher MYC, BCL2/MYC, and Ki67 protein expression levels, as well as a higher rate of post-chemotherapy bone marrow suppression rate (P<0.05). Compared to the syndrome of qi depression with phlegm obstruction, the syndrome of phlegm-blood stasis toxin exhibited lower Ki67 protein expression (P<0.05); the syndrome of yin deficiency with phlegm accumulation had higher β2-MG level, bone marrow infiltration rate, and rate of concurrent infections during chemotherapy, whereas PLT and NEUT levels and the rate of post-chemotherapy bone marrow suppression rate were lower (P<0.05). Compared to the syndrome of phlegm-blood stasis toxin, the syndrome of yin deficiency with phlegm accumulation had higher β2-MG level, whereas NEUT and the rate of post-chemotherapy bone marrow suppression were lower(P<0.05); the syndrome of lingering pathogen due to deficient vital qi exhibited a higher Ki67 protein expression (P<0.05). Compared to the syndrome of yin deficiency with phlegm accumulation, the syndrome of lingering pathogen due to deficient vital qi also showed a higher Ki67 protein expression(P<0.05).
Conclusion
The syndrome of yin deficiency with phlegm accumulation is relatively common in lymphoma. There is a correlation between TCM syndromes and Western medicine clinical indicators. The presence of heat signs in the syndromes may indicate active disease and poor prognosis, while the presence of strong pathogenic factors and weak vital qi in the syndromes may indicate a severer chemotherapy-related bone marrow suppression.
3.Effect of refractive status before small incision lenticule extraction surgery on postoperative accommodative function
Meiluo ZHANG ; Chunyu TIAN ; Qinghua YANG ; Liexi JIA ; Hongtao ZHANG ; Manmei LI ; Zhengqing DU ; Zhuo ZENG ; Xue WANG ; Wei ZHANG
International Eye Science 2025;25(2):323-327
AIM: To investigate the abnormal conditions and change patterns of accommodative facility in patients with different refractive states before and after small incision lenticule extraction(SMILE)surgery.METHODS:A prospective clinical cohort study was conducted. A total of 59 patients(118 eyes)who underwent SMILE surgery and had visual function files established in our hospital from June to December 2023 were randomly selected, including 37 males and 22 females, aged 18-35 years(with an average age of 25.19±5.65 years). According to the preoperative spherical equivalent(SE), they were divided into two groups: the low-to-moderate myopia group(SE≥-6.00 DS)with 40 patients(80 eyes), and the high myopia group(SE<-6.00 DS)with 19 patients(38 eyes). The monocular and binocular accommodative facility before surgery and at 1 wk and 1 mo after surgery were compared, and the changes in accommodative facility before and after SMILE surgery in the two groups of patients were analyzed.RESULTS:All surgeries were completed successfully. In the low-to-moderate myopia group, 33 cases(66 eyes)completed the 1-month follow-up after surgery, with a loss to follow-up rate of 17.5%(7/40). In the high myopia group, 15 patients(30 eyes)completed the 1-month follow-up after surgery, with a loss to follow-up rate of 21.1%(4/19). After SMILE surgery, the uncorrected visual acuity and SE of both low-to-moderate myopia and high myopia were significantly improved(all P<0.05). The accommodative facility of the right eyes in all the patients at 1 mo after surgery was better than that before surgery and at 1 wk after surgery(P=0.002, 0.006), the accommodative facility of the left eyes was significantly increased at 1 mo after surgery than that at 1 wk after surgery(P=0.005), and the binocular accommodative facility at 1 mo after surgery was significantly increased compared with that before surgery(P<0.017). Furthermore, there were statistical significance in accommodative facility of the right eyes in the low-to-moderate group at 1 mo compared with that before surgery and at 1 wk after surgery(P=0.011, 0.004); it was significantly increased in the left eyes at 1 mo after surgery compared with that at 1 wk after surgery(P=0.001), and binocular accommodative facility at 1 mo after surgery was significantly better than that before surgery(P<0.001). Furthermore, there was no statistical significance in the right, left and binocular accommodative facility of patients in the high myopia group(all P>0.017).CONCLUSION: After SMILE surgery, the monocular accommodative facility shows a transient decrease and then exceeds the preoperative level at 1 mo after surgery, and the binocular accommodative facility gradually improves after surgery. SMILE surgery has a positive impact on the monocular and binocular accommodative facility in patients with low-to-moderate myopia, but has no significant impact on the accommodative facility in patients with high myopia. It is of clinical significance to strengthen the detection of monocular and binocular accommodative facility before and after SMILE surgery.
4.Severity Assessment Parameters and Diagnostic Technologies of Obstructive Sleep Apnea
Zhuo-Zhi FU ; Ya-Cen WU ; Mei-Xi LI ; Ping-Ping YIN ; Hai-Jun LIN ; Fu ZHANG ; Yu-Xiang YANG
Progress in Biochemistry and Biophysics 2025;52(1):147-161
Obstructive sleep apnea (OSA) is an increasingly widespread sleep-breathing disordered disease, and is an independent risk factor for many high-risk chronic diseases such as hypertension, coronary heart disease, stroke, arrhythmias and diabetes, which is potentially fatal. The key to the prevention and treatment of OSA is early diagnosis and treatment, so the assessment and diagnostic technologies of OSA have become a research hotspot. This paper reviews the research progresses of severity assessment parameters and diagnostic technologies of OSA, and discusses their future development trends. In terms of severity assessment parameters of OSA, apnea hypopnea index (AHI), as the gold standard, together with the percentage of duration of apnea hypopnea (AH%), lowest oxygen saturation (LSpO2), heart rate variability (HRV), oxygen desaturation index (ODI) and the emerging biomarkers, constitute a multi-dimensional evaluation system. Specifically, the AHI, which measures the frequency of sleep respiratory events per hour, does not fully reflect the patients’ overall sleep quality or the extent of their daytime functional impairments. To address this limitation, the AH%, which measures the proportion of the entire sleep cycle affected by apneas and hypopneas, deepens our understanding of the impact on sleep quality. The LSpO2 plays a critical role in highlighting the potential severe hypoxic episodes during sleep, while the HRV offers a different perspective by analyzing the fluctuations in heart rate thereby revealing the activity of the autonomic nervous system. The ODI provides a direct and objective measure of patients’ nocturnal oxygenation stability by calculating the number of desaturation events per hour, and the biomarkers offers novel insights into the diagnosis and management of OSA, and fosters the development of more precise and tailored OSA therapeutic strategies. In terms of diagnostic techniques of OSA, the standardized questionnaire and Epworth sleepiness scale (ESS) is a simple and effective method for preliminary screening of OSA, and the polysomnography (PSG) which is based on recording multiple physiological signals stands for gold standard, but it has limitations of complex operations, high costs and inconvenience. As a convenient alternative, the home sleep apnea testing (HSAT) allows patients to monitor their sleep with simplified equipment in the comfort of their own homes, and the cardiopulmonary coupling (CPC) offers a minimal version that simply analyzes the electrocardiogram (ECG) signals. As an emerging diagnostic technology of OSA, machine learning (ML) and artificial intelligence (AI) adeptly pinpoint respiratory incidents and expose delicate physiological changes, thus casting new light on the diagnostic approach to OSA. In addition, imaging examination utilizes detailed visual representations of the airway’s structure and assists in recognizing structural abnormalities that may result in obstructed airways, while sound monitoring technology records and analyzes snoring and breathing sounds to detect the condition subtly, and thus further expands our medical diagnostic toolkit. As for the future development directions, it can be predicted that interdisciplinary integrated researches, the construction of personalized diagnosis and treatment models, and the popularization of high-tech in clinical applications will become the development trends in the field of OSA evaluation and diagnosis.
5.Effect of Zuogui Jiangtang Jieyu Formula on hippocampal H3K18la modification in a rat model of diabetes mellitus complicated with depression and prediction of related regulatory genes
Hui YANG ; Wei LI ; Shihui LEI ; Jinxi WANG ; Zhuo LIU ; Pan MENG ; Lin LIU ; Fan JIANG ; Yuhong WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(6):791-801
Objective:
To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la.
Methods:
Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la.
Results:
Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes.
Conclusion
ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.
6.Zedoarondiol Inhibits Neovascularization in Atherosclerotic Plaques of ApoE-/- Mice by Reducing Platelet Exosomes-Derived MiR-let-7a.
Bei-Li XIE ; Bo-Ce SONG ; Ming-Wang LIU ; Wei WEN ; Yu-Xin YAN ; Meng-Jie GAO ; Lu-Lian JIANG ; Zhi-Die JIN ; Lin YANG ; Jian-Gang LIU ; Da-Zhuo SHI ; Fu-Hai ZHAO
Chinese journal of integrative medicine 2025;31(3):228-239
OBJECTIVE:
To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment.
METHODS:
ApoE-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation.
RESULTS:
Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36.
CONCLUSION
Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals
;
MicroRNAs/genetics*
;
Exosomes/drug effects*
;
Plaque, Atherosclerotic/genetics*
;
Neovascularization, Pathologic/genetics*
;
Human Umbilical Vein Endothelial Cells/metabolism*
;
Humans
;
Blood Platelets/drug effects*
;
Apolipoproteins E/deficiency*
;
Thrombospondin 1/metabolism*
;
CD36 Antigens/metabolism*
;
Platelet Activation/drug effects*
;
Male
;
Mice
;
Mice, Inbred C57BL
7.Palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis: A new target for anti-myocardial fibrosis.
Xuewen YANG ; Yanwei ZHANG ; Xiaoping LENG ; Yanying WANG ; Manyu GONG ; Dongping LIU ; Haodong LI ; Zhiyuan DU ; Zhuo WANG ; Lina XUAN ; Ting ZHANG ; Han SUN ; Xiyang ZHANG ; Jie LIU ; Tong LIU ; Tiantian GONG ; Zhengyang LI ; Shengqi LIANG ; Lihua SUN ; Lei JIAO ; Baofeng YANG ; Ying ZHANG
Acta Pharmaceutica Sinica B 2025;15(9):4789-4806
Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.
8.Expert consensus on pulpotomy in the management of mature permanent teeth with pulpitis.
Lu ZHANG ; Chen LIN ; Zhuo CHEN ; Lin YUE ; Qing YU ; Benxiang HOU ; Junqi LING ; Jingping LIANG ; Xi WEI ; Wenxia CHEN ; Lihong QIU ; Jiyao LI ; Yumei NIU ; Zhengmei LIN ; Lei CHENG ; Wenxi HE ; Xiaoyan WANG ; Dingming HUANG ; Zhengwei HUANG ; Weidong NIU ; Qi ZHANG ; Chen ZHANG ; Deqin YANG ; Jinhua YU ; Jin ZHAO ; Yihuai PAN ; Jingzhi MA ; Shuli DENG ; Xiaoli XIE ; Xiuping MENG ; Jian YANG ; Xuedong ZHOU ; Zhi CHEN
International Journal of Oral Science 2025;17(1):4-4
Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans
;
Calcium Compounds/therapeutic use*
;
Consensus
;
Dental Pulp
;
Dentition, Permanent
;
Oxides/therapeutic use*
;
Pulpitis/therapy*
;
Pulpotomy/standards*
9.Expert consensus on management of instrument separation in root canal therapy.
Yi FAN ; Yuan GAO ; Xiangzhu WANG ; Bing FAN ; Zhi CHEN ; Qing YU ; Ming XUE ; Xiaoyan WANG ; Zhengwei HUANG ; Deqin YANG ; Zhengmei LIN ; Yihuai PAN ; Jin ZHAO ; Jinhua YU ; Zhuo CHEN ; Sijing XIE ; He YUAN ; Kehua QUE ; Shuang PAN ; Xiaojing HUANG ; Jun LUO ; Xiuping MENG ; Jin ZHANG ; Yi DU ; Lei ZHANG ; Hong LI ; Wenxia CHEN ; Jiayuan WU ; Xin XU ; Jing ZOU ; Jiyao LI ; Dingming HUANG ; Lei CHENG ; Tiemei WANG ; Benxiang HOU ; Xuedong ZHOU
International Journal of Oral Science 2025;17(1):46-46
Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans
;
Root Canal Therapy/adverse effects*
;
Consensus
;
Root Canal Preparation/adverse effects*
10.Lentivirus-modified hematopoietic stem cell gene therapy for advanced symptomatic juvenile metachromatic leukodystrophy: a long-term follow-up pilot study.
Zhao ZHANG ; Hua JIANG ; Li HUANG ; Sixi LIU ; Xiaoya ZHOU ; Yun CAI ; Ming LI ; Fei GAO ; Xiaoting LIANG ; Kam-Sze TSANG ; Guangfu CHEN ; Chui-Yan MA ; Yuet-Hung CHAI ; Hongsheng LIU ; Chen YANG ; Mo YANG ; Xiaoling ZHANG ; Shuo HAN ; Xin DU ; Ling CHEN ; Wuh-Liang HWU ; Jiacai ZHUO ; Qizhou LIAN
Protein & Cell 2025;16(1):16-27
Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans
;
Leukodystrophy, Metachromatic/genetics*
;
Pilot Projects
;
Genetic Therapy/methods*
;
Hematopoietic Stem Cell Transplantation
;
Male
;
Follow-Up Studies
;
Female
;
Lentivirus/genetics*
;
Child
;
Child, Preschool
;
Hematopoietic Stem Cells/metabolism*
;
Cerebroside-Sulfatase/metabolism*
;
Adolescent


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