更新于：2024-11-01

Thymidine kinase 2 deficiency

胸苷激酶2缺乏症

更新于：2024-11-01

基本信息

别名

Thymidine kinase 2 deficiency、Thymidine kinase 2 deficiency (disorder)

简介-

关联

项与胸苷激酶2缺乏症相关的药物

Deoxythymidine/Deoxycytidine

靶点-

作用机制-

在研机构

UCB SA

原研机构

Modis Therapeutics, Inc.初创企业

在研适应症

胸苷激酶2缺乏症

非在研适应症-

最高研发阶段申请上市

首次获批国家/地区-

首次获批日期1800-01-20

Doxribtimine

靶点-

作用机制-

在研机构

Zogenix, Inc.

原研机构

Zogenix, Inc.

在研适应症

胸苷激酶2缺乏症

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

Doxecitine

靶点-

作用机制-

在研机构

Zogenix, Inc.

原研机构

Zogenix, Inc.

在研适应症

胸苷激酶2缺乏症

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

项与胸苷激酶2缺乏症相关的临床试验

NCT04581733 / Withdrawn临床3期

A Phase 3b Single Arm Clinical Study to Evaluate the Efficacy and Safety of MT1621 in Nucleos(t)Ide Treatment Naïve Pediatric and Adolescent Subjects With Thymidine Kinase 2 (TK2) Deficiency

This is a Phase 3b, prospective, single-arm, multicenter, open-label treatment study of the efficacy and safety of MT1621 in pediatric and adolescent patients with thymidine kinase 2 deficiency (TK2d). In order to be eligible for this study, participants must have genetic confirmation of TK2d and must not have ever received MT1621 or nucleos(t)ides before entering the study.

开始日期2022-09-30

申办/合作机构

Zogenix, Inc.

NCT03845712 / Active, not recruiting临床2期

A Phase 2 Open-Label Study of Continuation Treatment With Combination Pyrimidine Nucleosides in Patients With Thymidine Kinase 2 Deficiency (TK2)

This is a Phase 2 prospective open-label treatment study of the safety and efficacy of doxecitine and doxribtimine in study participants with thymidine kinase 2 (TK2) deficiency who participated in the retrospective study MT-1621-101 [NCT03701568] or who were receiving nucleos(t)ide treatment and were approved by the Sponsor.

开始日期2019-07-05

申办/合作机构

UCB BioSciences, Inc.

NCT03701568 / CompletedN/A

A RETROspective Study of the Combination of Pyrimidine Nucleos(t)Ides in Patients With Thymidine Kinase 2 Deficiency (TK2)

This is a medical chart review study to collect information for patients who have been taking pyrimidine nucleosides for treatment of TK2 deficiency. Information from the time of onset of symptoms will be collected to describe the pre treatment course of TK2 deficiency.

开始日期2018-11-19

申办/合作机构

Zogenix, Inc.

100 项与胸苷激酶2缺乏症相关的临床结果

登录后查看更多信息

100 项与胸苷激酶2缺乏症相关的转化医学

登录后查看更多信息

0 项与胸苷激酶2缺乏症相关的专利（医药）

登录后查看更多信息

项与胸苷激酶2缺乏症相关的文献（医药）

2024-05-01·Mitochondrion

Remarkable clinical improvement with oral nucleoside treatment in a patient with adult-onset TK2 deficiency: A case report

Article

作者: Hernández-Voth, Ana ; Martin-Jimenez, Paloma ; Martin, Miguel A ; Bermejo-Guerrero, Laura ; Blázquez, Alberto ; Domínguez-González, Cristina ; Serrano-Lorenzo, Pablo

OBJECTIVESThymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive mitochondrial disorder. It manifests as a continuous clinical spectrum, from fatal infantile mitochondrial DNA depletion syndromes to adult-onset mitochondrial myopathies characterized by ophthalmoplegia-plus phenotypes with early respiratory involvement. Treatment with pyrimidine nucleosides has recently shown striking effects on survival and motor outcomes in the more severe infantile-onset clinical forms. We present the response to treatment in a patient with adult-onset TK2d.METHODSAn adult with ptosis, ophthalmoplegia, facial, neck, and proximal muscle weakness, non-invasive nocturnal mechanical ventilation, and dysphagia due to biallelic pathogenic variants in TK2 received treatment with 260 mg/kg/day of deoxycytidine (dC) and deoxythymidine (dT) under a Compassionate Use Program. Prospective motor and respiratory assessments are presented.RESULTSAfter 27 months of follow-up, the North Star Ambulatory Assessment improved by 11 points, he walked 195 m more in the 6 Minute-Walking-Test, ran 10 s faster in the 100-meter time velocity test, and the Forced Vital Capacity stabilized. Growth Differentiation Factor-15 (GDF15) levels, a biomarker of respiratory chain dysfunction, normalized. The only reported side effect was dose-dependent diarrhea.DISCUSSIONTreatment with dC and dT can significantly improve motor performance and stabilize respiratory function safely in patients with adult-onset TK2d.

2024-04-01·Neurology Genetics

Clinical and Genetic Analysis of Patients With TK2 Deficiency

Article

作者: Serrano-Lorenzo, Pablo ; Paradas, Carmen ; Galán-Rodriguez, Beatriz ; Carracedo, Angel ; Quesada-Espinosa, Juan F ; Amigo, Jorge ; Domínguez-González, Cristina ; Jaijo, Teresa ; Minguez, Pablo ; Muelas, Nuria ; Martí, Ramon ; Ceballos, Francisco ; Martín, Miguel A ; Bermejo-Guerrero, Laura ; Arenas, Joaquín ; Ayuso, Carmen ; Nascimento, Andres ; García-Arumí, Elena ; Blázquez, Alberto

ObjectivesThymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive disorder that stems from a perturbation of the mitochondrial DNA maintenance. Nucleoside treatment has recently shown promise as a disease-modifying therapy. TK2d was initially associated with rapidly progressive fatal myopathy in children featuring mitochondrial DNA depletion. Subsequently, less severe variants of the disease were described, with onset of symptoms during adolescence or adulthood and associated with the presence of multiple mtDNA deletions. These less severe phenotypes have been reported in only 15% of the approximately 120 patients described worldwide. However, some reports suggest that these juvenile and adult-onset presentations may be more common. The objective of this study was to describe the clinical phenotype in a sample of patients from Spain.MethodsThis study includes 53 patients harboring biallelic TK2 pathogenic variants, compiling data retrospectively from 7 Spanish centers. We analyzed allele frequency, investigated the most recent common ancestor of core haplotypes, and used the Runs of Homozygosity approach to investigate variant coalescence.ResultsSymptom onset distribution revealed that 32 patients (60%) experienced symptoms beyond 12 years of age. Approximately 30% of patients died of respiratory insufficiency, while 56% of surviving patients needed mechanical ventilation. Genetic analysis identified 16 distinct variants in TK2. Two variants, p.Lys202del and p.Thr108Met, exhibited significantly higher prevalence in the Spanish population than that reported in gnomAD database (86-fold and 13-fold, respectively). These variants are estimated to have originated approximately 16.8 generations ago for p.Thr108Met and 95.2 generations ago for p.Lys202del within the Spanish population, with the increase in frequency attributed to various forms of inbreeding. In late-onset cases, 46.9% carried the p.Lys202del variant.DiscussionThe higher frequency of TK2d in Spain can be partially attributed to the increased prevalence of 2 variants and consanguinity. Notably, in 60% of the cohort, the disease was late-onset, emphasizing the potential underdiagnosis of this subgroup of patients in other regions. Raising awareness of this potentially treatable disorder is of utmost importance because early interventions can significantly affect the quality of life and survival of affected individuals.

2023-10-17·Neurology

Pearls & Oy-sters: Case Report of a Patient With Adult-Onset Thymidine Kinase 2 Gene Deficiency

Article

作者: Karam, Chafic ; Ljungberg, Lovisa ; Goldstein, Amy ; Morganroth, Jennifer ; Kallish, Staci ; Quinn, Colin ; Price, Raymond S. ; Asher, Stephanie B.

项与胸苷激酶2缺乏症相关的新闻（医药）

2022-08-15

·BioSpace

Nuvig Therapeutics Expands Leadership Team with the Appointment of Dr. Joanne Quan as Chief Medical Officer

Aug. 15, 2022 13:00 UTC Physician-scientist and biopharmaceutical executive with extensive experience in novel drug development and pipeline strategy REDWOOD CITY, Calif.--(BUSINESS WIRE)-- Nuvig Therapeutics, Inc. a private biotech company developing novel therapeutics to restore immune homeostasis and treat chronic autoimmune diseases, announced today the appointment of Joanne Quan, M.D., as Chief Medical Officer. Dr. Quan has more than 25 years of experience advancing novel drug candidates in all stages of development, from preclinical compounds to marketed products. “Joanne has a passion and commitment to developing new therapies for patients with high unmet medical needs and has a successful track record in advancing novel drug candidates for a wide range of therapeutic areas, including autoimmune disorders and rare and orphan diseases,” said Pamela Conley, Ph.D., Chief Executive Officer and Cofounder of Nuvig Therapeutics. “In addition, Joanne has built nimble and creative teams and has led multiple successful collaborations and partnerships to support the progression of new therapies to commercialization.” Dr. Quan added, “What attracted me to Nuvig was the incredible science and the potential to develop therapies for multiple immunologic diseases, many of which have few or no treatment options. It’s exciting to join Nuvig at this stage as we refine the scientific and clinical strategy and build the company to maximize the reach of this novel approach. I look forward to demonstrating proof-of-concept as we move into the clinic.” Prior to Nuvig, Dr. Quan was Chief Medical Officer at Modis Therapeutics, a company focused on developing disease-modifying therapies for patients with rare genetic diseases. After Modis was acquired by Zogenix, Dr. Quan, as a member of the Executive Team, continued to lead drug development for mitochondrial diseases, including advancing nucleoside therapy for thymidine kinase 2 deficiency toward filing in U.S. and Europe. Before Modis, she held positions of increasing responsibility at Eiger Biopharmaceuticals, InterMune, Arena Pharmaceuticals, Bayhill Therapeutics, ALZA Corporation (Johnson and Johnson), Genentech, and PathoGenesis. Dr. Quan received a B.A. in molecular biology at the University of California, Berkeley and an M.D. at Stanford University School of Medicine. She completed a residency in Internal Medicine at Massachusetts General Hospital and a fellowship in Pulmonary and Critical Care Medicine at the University of Washington. About Nuvig Therapeutics Nuvig Therapeutics is advancing innovative and transformational therapies that are designed to induce natural mechanisms to restore immune homeostasis, rebalance immune function following inflammation, and provide better treatments for patients. Nuvig is building a pipeline of novel immune therapeutics for chronic inflammatory and autoimmune diseases. For more info, visit .

合作