Ataxia Telangiectasia (Louis Bar Syndrome)

An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ATAXIA; TELANGIECTASIS of CONJUNCTIVA and SKIN; DYSARTHRIA; B- and T-cell immunodeficiency, and RADIOSENSITIVITY to IONIZING RADIATION. Affected individuals are prone to recurrent sinobronchopulmonary infections, lymphoreticular neoplasms, and other malignancies. Serum ALPHA-FETOPROTEINS are usually elevated. (Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23).

Also Known As:

Networked: 4175 relevant articles (54 outcomes, 226 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Neoplasms (Cancer)
2.	Breast Neoplasms (Breast Cancer)
3.	Ataxia (Dyssynergia)
4.	Atrophy
5.	Ovarian Neoplasms (Ovarian Cancer)

Experts

1.	Lavin, Martin F: 32 articles (01/2022 - 08/2002)
2.	Shiloh, Yosef: 29 articles (01/2022 - 01/2002)
3.	Paull, Tanya T: 26 articles (12/2021 - 04/2004)
4.	Gatti, Richard A: 22 articles (11/2021 - 02/2003)
5.	Lees-Miller, Susan P: 21 articles (07/2021 - 12/2002)
6.	Jeggo, Penny A: 21 articles (01/2021 - 09/2002)
7.	Chessa, Luciana: 20 articles (01/2021 - 08/2002)
8.	Khanna, Kum Kum: 18 articles (01/2017 - 02/2002)
9.	Chen, Junjie: 17 articles (11/2020 - 01/2002)
10.	Kastan, Michael B: 17 articles (01/2019 - 02/2002)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Ataxia Telangiectasia:

1.	Phosphotransferases (Kinase)IBA 10/20/2023 - "Genetic or pharmacologic disruption of the DNA damage response kinase Ataxia-telangiectasia mutated (ATM) enhanced the efficacy of focal brain irradiation, extending mouse survival. " 01/01/2018 - "During this process, ZEB1 transcriptionally activated the expression of ataxia-telangiectasia mutated (ATM) kinase by forming a ZEB1/p300/PCAF complex on its promoter, leading to increased homologous recombination (HR)-mediated DNA damage repair and the clearance of DNA breaks. " 06/01/2023 - "Ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) have been shown to be synthetic lethal with loss of function (LOF) of ataxia telangiectasia-mutated (ATM) kinase, and preclinical studies have identified ATRi-sensitizing alterations in other DNA damage response (DDR) genes. " 01/01/2021 - "By combining mass spectrometry-based analysis of the VCP interactome and phospho-signaling studies, we determined that VCP is important for ataxia telangiectasia mutated (ATM) kinase activation and subsequent DNA repair through homologous recombination in AML. " 05/01/2015 - "This study was focused on the role of two major DDR-related factors, ataxia telangiectasia-mutated (ATM) and ATM- and RAD3-related (ATR) kinases, in the maintenance of intestinal stem cells (ISCs) in the adultDrosophila midgut. "
2.	Proteins (Proteins, Gene)FDA Link 10/09/2018 - "Mechanistically, MARS preferentially bound to and modified ataxia-telangiectasia and Rad3-related protein (ATR), inhibited ATR and its downstream effectors checkpoint kinase-1 and p53, and relieved cell-cycle arrest and decreased DNA damage-induced apoptosis by disrupting the binding of ATR-interacting protein to ATR. " 01/01/2022 - "Interest in the function of ataxia-telangiectasia-mutated protein (ATM) is extensively growing as evidenced by preclinical studies that continuously link ATM with new intracellular pathways. " 08/01/2018 - "The purpose of this study was to investigate whether the protein expressions of ataxia telangiectasia mutated (ATM), p53, and ATM-mediated phosphorylated p53 are related to patient survival in ACC. " 04/01/2017 - "The goal of this paper is to study how the exposure to low dose radiation affects the human body by observing the signaling pathway associated with Ataxia Telangiectasia mutated (ATM) using Reverse-Phase Protein Array (RPPA) and isogenic human Ataxia Telangiectasia (A-T) cells under different amounts and durations of IR exposure. " 09/01/2013 - "In the present study, we investigated the changes of HR DNA repair proteins (ataxia-telangiectasia-mutated; ATM, ATM and Rad3-related; ATR), NHEJ repair proteins (Ku70/80), cell cycle regulators (Chk1, Chk2), and apoptosis marker (p53/p-p53) were determined in H. "
3.	DNA (Deoxyribonucleic Acid)IBA 06/01/2013 - "DNA molecules with the TR sequences constrained in the T-shaped HP conformation at one or both ends were subject to a loss of gene expression, which was partially relieved in ataxia telangiectasia mutated (ATM(-/-)) cells. " 01/01/2019 - "Our study furthers our understanding of neurodegeneration in A-T and highlights the role of cytosolic DNA in the innate immune response.SIGNIFICANCE STATEMENT Conventionally, the immune deficiencies found in ataxia-telangiectasia (A-T) patients are viewed as defects of the B and T cells of the acquired immune system. " 05/01/2018 - "Mechanistic studies showed that Iso triggered cell apoptosis by inducing DNA double-stranded breaks and blocking the initiation process of homologous recombination repair, which was related to the attenuation of ataxia telangiectasia mutated (ATM) activation and inhibiting the binding of phosphorylated ataxia telangiectasia mutated (pATM) and the MRE11-RAD50-NBS1 (MRN) complex. " 03/26/2015 - "In this study, we show that high levels of TACC3 lead to the accumulation of DNA double-strand breaks (DSBs) and disrupt the normal cellular response to DNA damage, at least in part, by negatively regulating the expression of ataxia telangiectasia mutated (ATM) and the subsequent DNA damage response (DDR) signaling cascade. " 11/01/2011 - "Ataxia telangiectasia mutated (ATM) has multiple functions in homologous recombination (HR) and nonhomologous end joining (NHEJ), which lead to conflicting data regarding its DNA double-strand break-repair (DSBR) functions in previous studies. "
4.	DNA-Activated Protein KinaseIBA 11/01/2022 - "Combined ataxia telangiectasia mutated and DNA-dependent protein kinase inhibition radiosensitizes Madin-Darby canine kidney cells." 12/01/2021 - "This is especially true for drugs targeting the catalytic subunit of DNA-dependent protein kinase, which is a core component of the nonhomologous end-joining DNA repair pathway, and ataxia telangiectasia mutated, which coordinates cell cycle arrest, apoptosis, and DNA repair functionalities after radiation exposure. " 01/01/2018 - "Targeted knockdown of ATM (ataxia telangiectasia mutated) and ATR (ataxia telangiectasia and Rad3 related; HR regulators) and DNA-dependent protein kinase (NHEJ regulator) mRNAs revealed that the attenuation of HR or both HR and NHEJ regulators severely impaired blastocyst formation and quality. " 01/01/2016 - "Dephosphorylated NPM impairs the signaling of oxidative stress-induced DNA damage via inhibition of the phosphorylation of ataxia-telangiectasia mutated and DNA-dependent protein kinase catalytic subunit. " 09/01/2013 - "Under these conditions, ataxia-telangiectasia mutated activation and accumulation of DNA-dependent protein kinase, catalytic subunit pS2056 foci suggested an increased number of DSBs processed by nonhomologous end-joining (NHEJ). "
5.	Poly(ADP-ribose) Polymerase InhibitorsIBA 01/01/2023 - "We found that MAPK inhibitor resistant melanoma cells are particularly sensitive to PARP inhibitor treatment due to a lower basal expression of the DNA damage sensor ataxia-telangiectasia mutated (ATM). " 01/01/2016 - "Deficiency in the DNA damage response factor ataxia-telangiectasia mutated (ATM) can also sensitize tumors to PARP inhibitors, raising the question of whether the presence or absence of 53BP1 can predict sensitivity of ATM-deficient breast cancer to these inhibitors. " 12/15/2018 - "Furthermore, the authors explore the efficacy of combined ataxia telangiectasia and Rad3-related kinase and PARP inhibitors as a strategy to leverage these mechanisms and overcome radiation resistance.See" 09/01/2021 - "These studies revealed that loss of ATRX confers sensitivity to poly(ADP)-ribose polymerase (PARP) inhibitors, which was linked to an increase in replication stress, as detected by increased activation of the ataxia telangiectasia and Rad3-related (ATR) signaling axis. " 12/01/2023 - "PARP inhibitors may also increase exogenous replication stress and thereby increase sensitivity to inhibitors of ataxia telangiectasia and Rad3-related (ATR) protein. "
6.	Betamethasone (Celestone)FDA Link 04/01/2011 - "This study provides Class IIIA evidence that betamethasone at very low dosage is effective in improving neurological signs of patients affected with ataxia-telangiectasia." 04/01/2011 - "Efficacy of very-low-dose betamethasone on neurological symptoms in ataxia-telangiectasia." 02/01/2021 - "In Ataxia-Telangiectasia, Oral Betamethasone Administration Ameliorates Lymphocytes Functionality through Modulation of the IL-7/IL-7Rα Axis Paralleling the Neurological Behavior: A Comparative Report of Two Cases." 11/01/2019 - "Although these findings are in agreement with previous studies suggesting that short-term betamethasone treatment transiently benefits patients with ataxia telangiectasia, the long-term benefits and risks should be carefully considered." 11/01/2019 - "The aim of this study was to evaluate the long-term effects, benefits, and adverse effects of low-dose betamethasone in ataxia telangiectasia. "
7.	nicotinamide-beta-ribosideIBA 10/29/2023 - "Supplementation of nicotinamide riboside (NR) ameliorates neuropathology in animal models of ataxia telangiectasia (A-T). " 12/01/2021 - "Treatment of animal models with ataxia telangiectasia (A-T) with nicotinamide riboside (NR) improved their neurological outcome and survival. " 01/01/2023 - " the effects on motor and speech improvement might be partly explained by development, our study replicates the previous finding of a positive effect of nicotinamide riboside treatment in ataxia telangiectasia. " 10/29/2023 - "Long-Term Nicotinamide Riboside Use Improves Coordination and Eye Movements in Ataxia Telangiectasia." 01/01/2023 - "Given the absence of adverse effects, we strongly encourage to consider nicotinamide riboside in all individuals with ataxia telangiectasia."
8.	Ataxia Telangiectasia Mutated ProteinsIBA 12/01/2003 - "Improved diagnostic testing for ataxia-telangiectasia by immunoblotting of nuclear lysates for ATM protein expression." 01/01/2021 - "A large number of studies have shown that DNA damage response (DDR) transducer ataxia-telangiectasia mutated (ATM) protein can also be activated by ROS, and its downstream signaling pathway is involved in autophagy regulation. " 10/30/2020 - "A major finding of our study was the intense and highly specific nuclear expression of Ataxia Telangiectasia Mutated (ATM) protein within melanocytes in anagen hair follicle bulbs. " 06/01/2000 - "Previous studies on a limited number of ataxia-telangiectasia (A-T) patients with detectable levels of intracellular ATM protein have suggested a genotype/phenotype correlation. " 06/01/2000 - "Ataxia-telangiectasia: phenotype/genotype studies of ATM protein expression, mutations, and radiosensitivity."
9.	Protein Kinases (Protein Kinase)IBA 03/01/2016 - "ATM, mutation of which causes Ataxia telangiectasia, has emerged as a cardinal multifunctional protein kinase during past two decades as evidenced by various studies from around the globe. " 02/01/2015 - "In the present study, we identified Fe65 Ser(228) as a novel target of the ATM (ataxia telangiectasia mutated) and ATR (ataxia-telangiectasia- and Rad3-related protein) protein kinases, in a reaction that occurred independently of APP. " 04/01/2006 - "Insight into the functions of Nbs1 in the DNA damage response mediated by the protein kinase, ataxia telangiectasia mutated, has been provided by recent studies. " 11/05/1999 - "Results from this study indicate that the checkpoint protein kinase ATM (mutated in ataxia telangiectasia) was required for phosphorylation of Brca1 in response to ionizing radiation. " 01/01/2023 - "Yeast Mec1, and its mammalian ortholog, Ataxia-Telangiectasia and Rad3-related, are giant protein kinases central to replication stress and double strand DNA break repair. "
10.	Histones (Histone)IBA 04/24/2007 - "We find that gamma-irradiation activates the ataxia telangiectasia mutated-associated DNA damage response pathway in the HPECs but that the clearance of phosphorylated histone H2AX (gammaH2AX) foci is delayed. " 01/15/2023 - "Moreover, a decrease in E2F4 expression increased phosphorylated H2A.X variant histones and activated ataxia telangiectasia mutated (ATM) and p53-p21 pathway. " 01/01/2018 - "Here, we report that linker histone H1.2 is an essential regulator of ataxia telangiectasia mutated (ATM) activation. " 01/01/2016 - "The expression of gamma-H2A histone family, member X (γH2AX) was dramatically elevated in the CD147-negative cell lines after irradiation, but the expression of ataxia-telangiectasia mutated (ATM) was not different between the two groups. " 10/01/2012 - "The cytotoxicity of these combinations correlates with the activation of the ataxia telangiectasia mutated-CHK2 pathway, phosphorylation of KRAB-associated protein-1, epigenetic changes such as methylation and acetylation of histone 3, and activation of apoptosis. "

Therapies and Procedures

1.	Therapeutics 03/01/2015 - "T-cell ALL in ataxia telangiectasia cured with only 7 weeks of anti-leukemic therapy." 12/01/2019 - "Ataxia-telangiectasia is a progressive disease with no established therapy; so, it necessitates early diagnosis and follow-up of the patients. " 10/25/2016 - "To identify genetic targets that can sensitize AML cells to killing by FLT3 inhibitors, we performed a genome-wide RNA interference (RNAi)-based screen that identified ATM (ataxia telangiectasia mutated) as being synthetic lethal with FLT3 inhibitor therapy. " 01/01/2012 - "A recent challenge for investigators studying the progressive neurological disease ataxia-telangiectasia (A-T) is to identify mutations whose effects might be alleviated by mutation-targeted therapies. " 03/01/2010 - "As their actions are independent of p53 or ataxia telangiectasia mutated (ATM) function, agents that act by such mechanisms are promising to overcome resistance to current CLL therapy. "
2.	Radiotherapy 04/01/2016 - "Studies on associations between ataxia telangiectasia-mutated (ATM) polymorphisms and late radiotherapy-induced adverse events vary in clinical settings, and the results are inconsistent.We" 10/01/2021 - "In combination, the clinical cases and laboratory experiments are valuable information in the discussion whether radiotherapy is absolutely contraindicated in BS, which is the Case in other DNA repair syndromes like Ataxia Telangiectasia and Artemis." 10/01/2020 - "Severe reaction to radiotherapy provoked by hypomorphic germline mutations in ATM (ataxia-telangiectasia mutated gene)." 09/02/2017 - "Evidences suggested the activation of Ataxia telangiectasia mutated (ATM) pathway and Smad pathway are 2 of the important crucial mediators in the function of radiotherapy. " 07/11/2017 - "Severe Late Toxicity After Adjuvant Breast Radiotherapy in a Patient with a Germline Ataxia Telangiectasia Mutated Gene: Future Treatment Decisions."
3.	Drug Therapy (Chemotherapy) 09/01/1988 - "Children with ataxia telangiectasia have a high probability of developing acute lymphoblastic leukaemia, and have increased sensitivity to chemotherapy and irradiation. " 07/01/2017 - "Western blotting results showed that intermittent LDIR pretreatment apparently activated the ATM/p53 (ataxia telangiectasia mutated, ATM) pathway in radiotherapy; it also activated ERK and p38MAPK pathways in chemotherapy. " 07/29/2005 - "Further, BM transplantation restores oocyte production in wild-type mice sterilized by chemotherapy, as well as in ataxia telangiectasia-mutated gene-deficient mice, which are otherwise incapable of making oocytes. " 11/01/2022 - "Ataxia-telangiectasia-mutated and Rad3-related (ATR) is master regulator of the DNA-damage response that, through multiple mechanisms, can promote cancer cell survival in response to replication stress from sources, including chemotherapy and radiation. " 01/01/2019 - "Although the mechanism by which EBV manipulates ataxia telangiectasia mutation (ATM)-mediated DNA damage response in NPC has been extensively studied, the relationship between ATR (ATM and Rad-3 related) and EBV infection is largely unexplored, and also the role of ATR in chemotherapy resistance in EBV-positive NPC has not been specifically reported. "
4.	Investigational Therapies (Experimental Therapy) 11/01/2022 - "The discovery of innovative therapies targeting essential components of DNA damage signaling and repair pathways such as ataxia telangiectasia mutated and Rad3 related Checkpoint kinase 1 (ATR-CHK1)has offered a possibility of significant therapeutic improvement in oncology. "
5.	Phototherapy (Light Therapy) 12/01/2016 - "The aim of this project was to investigate whether inhibition of Ataxia Telangiectasia and Rad3 related kinase (ATR) may enhance efficacy of phototherapy. "