A Phase 1/2, Multi-regional, Single-Arm, Open-Label, Dose-Finding Clinical Trial to Evaluate the Safety, Tolerability and Efficacy of Gene Therapy for Leber's Hereditary Optic Neuropathy (LHON) Associated With ND1 Mutation

The objective of this clinical study is to evaluate the safety, tolerability and preliminary efficacy of NFS-02 in the treatment of LHON caused by mitochondrial ND1 gene mutation. This study will enroll subjects aged ≥ 18 years old and ≤ 75 years old to receive a single unilateral intravitreal (IVT) injection of NFS-02 to evaluate its safety, tolerability and preliminary efficacy. The clinical manifestations of all subjects are to be reduced visual acuity caused by LHON associated with ND1 mutation, with laboratory test showing G3460A mutation (a CLIA-certified laboratory) and reduced visual acuity lasted for > 6 months and < 10 years.

Start Date15 Aug 2023

Sponsor / Collaborator

纽福斯生物科技有限公司

CTR20232203

/ TerminatedPhase 1/2

一项评估基因治疗ND1突变相关的Leber遗传性视神经病变（LHON）的安全性、耐受性和有效性的1/2期、多区域、单臂、开放标签、剂量探索的临床研究

[Translation] A Phase 1/2, multi-regional, single-arm, open-label, dose-finding clinical study to evaluate the safety, tolerability, and efficacy of gene therapy for ND1 mutation-associated Leber hereditary optic neuropathy (LHON)

本临床研究的目的是评估 NFS-02眼用注射液治疗线粒体 ND1基因突变引起的 LHON的安全性、耐受性和初步疗效。本研究将入组年龄≥ 18岁且≤ 75岁的受试者，并让其接受单次 NFS-02单侧玻璃体内（ IVT）注射，以评估其安全性、耐受性和有效性。所有受试者的临床表现为 ND1突变相关的 LHON引起的视力下降，突变由实验室（经 CLIA认证的实验室）检测为 G3460A位点突变，且视力下降持续时间 >6个月且 <10年。目前，尚无针对LHON受试者的有效治疗。开发具有新作用机制的药物被认为对未来的临床实践具有重要意义。本研究可以为验证这种新型疗法的安全性、耐受性和有效性提供依据。

[Translation]

The purpose of this clinical study is to evaluate the safety, tolerability and preliminary efficacy of NFS-02 ophthalmic injection in the treatment of LHON caused by mitochondrial ND1 gene mutations. This study will enroll subjects aged ≥ 18 years and ≤ 75 years and allow them to receive a single unilateral intravitreal (IVT) injection of NFS-02 to evaluate its safety, tolerability and efficacy. All subjects have clinical manifestations of visual loss caused by LHON associated with ND1 mutations, and the mutation is detected by the laboratory (CLIA-certified laboratory) as G3460A site mutation, and the duration of visual loss is >6 months and <10 years. Currently, there is no effective treatment for LHON subjects. The development of drugs with new mechanisms of action is considered to be of great significance to future clinical practice. This study can provide a basis for verifying the safety, tolerability and efficacy of this new therapy.

Start Date02 Aug 2023

Sponsor / Collaborator

纽福斯生物科技有限公司

[+1]

JPRN-jRCTs041220041

/ CompletedPhase 1IIT

A study on the safety and utility of a novel mitochondrial function PET tracer [18F]BCPP-BF in healthy subjects: comparison with the first generation [18F]BCPP-EF

Start Date21 Sep 2022

Sponsor / Collaborator

Hamamatsu Photonics KK

100 Clinical Results associated with MT-ND1 x Mitochondrial complex I (NADH dehydrogenase)

100 Translational Medicine associated with MT-ND1 x Mitochondrial complex I (NADH dehydrogenase)

0 Patents (Medical) associated with MT-ND1 x Mitochondrial complex I (NADH dehydrogenase)

1,121

Literatures (Medical) associated with MT-ND1 x Mitochondrial complex I (NADH dehydrogenase)

01 Oct 2025·Parasitology International

New morphological, biological, and molecular insights into Taenia talicei (Cestoda: Taeniidae), adding the dog (Canis lupus familiaris) and Andean fox (Lycalopex culpaeus) as definitive hosts, and new records of intermediate hosts in Peru

Article

Author: Pacheco, Joel I ; Gomez-Puerta, Luis A ; Gonzalez, Armando E ; Angulo-Tisoc, José M ; Rossin, M Alejandra

Taenia talicei is a cestode endemic to South America that was originally described based on its metacestodes. The adult strobilus was described after being obtained through experimental infection in dogs. Despite this, the natural definitive host for this cestode, as well as its genetic information, remained unknown. The objective of this study is to investigate the role of the domestic dog, the Andean fox (Lycalopex culpaeus), and other species of rodents in the life cycle of T. talicei. Molecular analysis of the mitochondrial genes of cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 1 (nad1) was also carried out in the cestodes. For this, 13 adult cestodes and five metacestodes were collected from a domestic dog (n = 6), an Andean fox (n = 7), a northern viscacha (Lagidium peruanum) (n = 1), a yellow-rumped leaf-eared mouse (Phyllotis xanthopygus) (n = 3), and a robust tuco-tuco (Ctenomys tuconax) (n = 1). Various features of the scolex and rostellar hooks were analyzed using morphological methods. The molecular characterization of cox1 and nad1 was analyzed by standard PCR protocols. All parasites were identified as T. talicei by looking at their diagnostic features, e.g., size of their rostellar hooks, distribution of testes, and the shape of their metacestodes (fimbriocercus and polycephalic metacestodes). The analysis of the cox1 and nad1 mitochondrial genes showed 99 % and 100 % identity between them, respectively. The phylogenetic analysis indicated that T. talicei is closely related to Taenia polyacantha. Our findings confirm the domestic dog and the Andean fox as the definitive hosts and indicate that T. talicei has both a domestic and wild life cycle, as well as the participation of new species of rodents in their life cycle.

01 Jul 2025·Veterinary Parasitology

From selection to resistance: Mitochondrial findings in hookworm evolution under drug pressure

Article

Author: Rabelo, Élida Mara Leite ; da Silva Medeiros, Celi ; Costa, João Alexsander Silva ; Furtado, Luis Fernando Viana

Single nucleotide polymorphisms (SNPs) in codons 134, 167, 198, and 200 of the β-tubulin isotype 1 gene are associated with benzimidazole resistance in nematodes. Our group previously selected an Ancylostoma ceylanicum strain resistant to albendazole through drug-induced selective pressure, derived from a wild-type strain maintained under laboratory conditions for over 15 years. This study aimed to investigate mitochondrial genetic variability in the resistant strain compared to its wild-type counterpart. A total of 151 worms from both strains, collected during and 42 months after the selection process, were analyzed for partial sequences of the mitochondrial COI and NAD1 genes. Nucleotide variations were detected exclusively in the resistant strain, with low divergence levels of 0.16 % (1/612 bp) in COI and 0.25 % (1/398 bp) in NAD1. All COI substitutions were synonymous, while NAD1 presented one nonsynonymous mutation. Phylogenetic analyses based on Maximum Likelihood and Bayesian inference revealed strong clustering between resistant and wild-type laboratory samples (COI: 99 % bootstrap; NAD1: 96 %), distinct from field-derived sequences. These findings suggest that genetically homogeneous populations, resulting from isolation and restricted gene flow, may be more susceptible to genetic pressures, including selection, potentially leading to the establishment of resistant parasites. This study underscores the role of population genetics in the evolution of drug resistance and emphasizes the importance of managing genetic diversity to mitigate resistance development.

01 Jun 2025·Cryobiology

Ellagic acid maintains post-thaw goat sperm quality via protecting mitochondrial function from ROS damage

Article

Author: Ding, Kexin ; Kamel, Ahmed Mohamed ; Kou, Xin ; Min, Lingjiang ; Li, Wenjia ; Bastawy, Eslam M ; Zhu, Zhendong

This study aimed to investigate the effects of ellagic acid (EA), an antioxidant, on goat sperm quality after freezing and thawing. Goat semen was frozen using Tris-citric acid-glucose (TCG) extender containing 0, 1.25, 2.5, 5, and 10 μM of EA. Egg yolk represented 20 % (v/v) and glycerol represented 5 % (v/v) of the extender's final concentration. Goat sperm post-thaw motility, acrosome integrity, plasma membrane integrity, mitochondrial activity, ATP content, NADH/NAD⁺ levels, and NADH-CoQ activity were evaluated. Moreover, to elucidate how EA enhanced the goat sperm characteristics, the post-thaw sperm mitochondrial reactive oxygen species (ROS) level, malondialdehyde (MDA) level, oxidative DNA damage, apoptosis, levels of NADH dehydrogenase 1 (MT-ND1) and NADH dehydrogenase 6 (MT-ND6) proteins, and the 4-hydroxynonenal (4-HNE) level were also measured after thawing. The results demonstrated that motility, plasma membrane integrity, and acrosome integrity rates were enhanced in the group treated with 5 μM of EA compared to the other concentrations (0 μM, 1.25 μM, 2.5 μM, 5, and 10 μM). Moreover, mitochondrial activity and ATP content were notably superior in the 5 μM EA group compared to all other treatment groups, along with a considerable decrease in ROS and MDA levels. The 4-HNE level and oxidative DNA damage in sperm were also reduced by EA supplementation. Additionally, it was found that EA (5 μM) significantly (p < 0.05) decreased sperm apoptosis levels. Furthermore, the addition of 5 μM EA maintained the post-thaw sperm MT-ND1 and MT-ND6 levels and reduced the negative impact of ROS on MT-ND1 and MT-ND6, thereby sustaining mitochondrial function for ATP generation. These results suggest that ellagic acid supplementation could maintain goat post-thaw sperm quality by reducing ROS damage and maintaining mitochondrial function for ATP generation. Antioxidant treatments, such as ellagic acid are a useful tool for maintaining frozen-thawed sperm quality.

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