30 results about "Ataxia-telangiectasia" patented technology

Novel methods are provided for identifying heterozygous carriers of autosomal recessive disorders such as Ataxia telangiectasia.

Disclosed are compounds and pharmaceutically acceptable salts thereof that may be used in the treatment of subjects in need thereof. The compounds disclosed herein may be inhibitors of Ataxia-telangiectasia and RAD-3-related protein kinase (ATR). Also disclosed are pharmaceutical compositions containing the compounds or pharmaceutically acceptable salts thereof and methods of their preparation and use.

ATM kinase is shown to regulate proteasome-mediated protein turnover through suppression of the expression of the ubiquitin-like protein ISG15 (Interferon Stimulated Gene 15). Silencing of the ISG15 pathway restored both the ubiquitin and autophagy pathways, and the UV-mediated degradation of their substrates in A-T cells. The ATM kinase negatively regulates the ISG15 pathway, and the constitutively elevated ISG15 pathway induces proteinopathy in A-T cells, and in A-T patients. These findings indicate that proteasome-mediated protein degradation is impaired in A-T cells due to elevated expression of the ISG15 conjugation pathway, which contributes to progressive neurodegeneration in A-T patients. The ISG15 pathway is a new target for both detection and treatment of A-T Inhibitors if ISG15 expression can be used to inhibit or attenuate neurodegeneration in A-T patients. In addition, an inhibitor of the early phase of autophagy, 3-MA, was shown to be effective in decreasing the impaired proteasome-mediated protein degradation in A-T cells, and thus would be effective in decreasing the neurodegeneration in A-T patients.

The current invention provides new methods and means for the prevention and treatment of ageing-related symptoms and diseases. The invention discloses Mannitol 5 and / or proline containing compositions that are particularly useful for the treatment of premature ageing related symptoms in mammalian subjects suffering from genetic defects in DNA damage response and genome maintenance pathways. Humans suffering from Cockayne syndrome (CS), Xerodema pigmentosum (XP), combined XPCS, trichothiodystrophy (TTD), COFS (cerebro-oculo-facio-skeletal syndrome), 10 XFE disorder (Xpf-Erccl syndrome), Bloom Syndrome (BS), Werner Syndrome (WS), Ataxia telangiectasia (AT), Fanconi Anemia (FA), Hutchinson Guilford Progeria (HGP) may be treated with pharmaceutical compositions comprising mannitol and / or proline according to this invention.

Disclosed is treatment of genetic neurodegenerative or neurodevelopmental diseases that are caused by or associated with nonsense mutations or premature termination codons using macrolides. Further disclosed are methods for identifying agents that induce read-through of nonsense mutations and premature termination codons and uses thereof.

In some embodiments, disclosed herein are oligomeric compounds which include one or more tricyclo-deoxyribonucleic acid (tc-DNA) nucleosides and one or more 2′-modified ribonucleic acid (2′-modified-RNA) nucleosides, and which optionally also include one or more non-nucleotides, each of which is joined by a plurality of internucleoside linkages, including pharmaceutical compositions and methods of using the pharmaceutical compositions for the treatment of diseases including Duchenne muscular dystrophy treatment of familial dysautonomia, spinal muscular atrophy, ataxia telangiectasia, congenital disorder of glycosylation, fronto-temporal dementia, Parkinsonism linked to chromosome 17, Niemann-Pick disease type C, neurofibromatosis type 1, neurofibromatosis type 2, megalencephalic leukoencephalopathy with subcortical cysts type 1, Pelizaeus-Merzbacher disease, Pompe disease, myotonic dystrophy type 2 (DM2 or proximal myotonic myopathy), and myotonic dystrophy type 1 (DM1 or Steinert disease).

The present invention relates to a process for preparing erythrocytes loaded with one or more substance of pharmaceutical interest. The present invention is also directed to loaded erythrocytes thus obtained and pharmaceutical compositions comprising said population of loaded erythrocytes as well as therapeutic application thereof, in particular in the treatment of Ataxia telangiectasia.

The present invention relates to a novel procedure for evaluating the response of patients affected by Ataxia Talangiectasia (A-T) to glucocorticoids treatment. In particular, the procedure provides a step of qualitative and / or quantitative identification in the blood of said patients of the expression of a mRNA variant of the ATM (Ataxia-Talangiectasia-Mutated) gene produced by non-canonical splicing induced by glucocorticoid (GC). In fact, it was demonstrated that mRNA variant expression is present in the blood of patients who responded positively to treatment with GC.

Disclosed are compounds of formula (I) or a pharmaceutically acceptable salt thereof wherein-is a single bond and each Y is N or CR4; or-absent and each Y is NRY, carbonyl or C (RY) 2 wherein each R1 is H or optionally substituted C1-6 alkyl; r1 is optionally substituted C1-6 alkyl or H; r3 is an optionally substituted heteroaryl group with 1 to 9 carbon atoms or an optionally substituted heteroaryl group with 1 to 6 alkyl groups with 1 to 9 carbon atoms; each R4 is hydrogen, halogen, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, or an optionally substituted C2-6 alkynyl group; x is hydrogen or halogen; and R2 is as defined in claim 1. Also disclosed are pharmaceutical compositions containing the compounds of formula (I) and methods of making the same. The compounds of formula (I) may be inhibitors of ataxia telangiectasia and RAD-3 associated protein kinase (ATR) and are useful in the treatment of diseases or conditions such as cancer.

The invention provides crystals, pharmaceutical compositions and applications of the compound N-butyl-2,2'-imino-bis(8-quinolinamine). The crystalline compound N-butyl-2,2'-imino-bis(8-quinolinamine) of the present invention has good medicinal properties, and can be used to treat diseases related to metal ion metabolic imbalance, as well as disorders including Tau protein metabolism, Beta-amyloid-related disorders such as amyotrophic lateral sclerosis, spinal muscular atrophy, ataxia-telangiectasia, Creutzfeldt-Jakob disease, Huntington's disease, cerebellar atrophy, multiple sclerosis , Parkinson's disease, Alzheimer's disease, primary lateral sclerosis and other diseases including neurodegenerative diseases.