Sentences with phrase «mutant huntingtin in»

Given the adult onset and dysfunction and death of adult neurons characterizing HD, most studies have focused on the toxic effects elicited by mutant huntingtin in post-mitotic neurons.

The phase 1 / 2a study of IONIS - HTTRx was recently completed and showed the therapy to be safe and well - tolerated but also showed it's ability to reduce the level of mutant huntingtin in a dose dependent manner in Huntington's Disease patients.

In an announcement likely to stand as one of the biggest breakthroughs in Huntington's disease since the discovery of the HD gene in 1993, Ionis and Roche today announced that the first human trial of a huntingtin - lowering drug, IONIS - HTTRx, demonstrates that it reduces mutant huntingtin in the nervous system, and is safe and well - tolerated.

The international team of scientists from University College London, IRBM Promidis, University of British Columbia, and CHDI Foundation developed a new ultra-sensitive test using the Singulex SMC Technology Erenna Immunoassay system that is able to detect mutant huntingtin in the cerebrospinal fluid (CSF) of HD patients, including some who carry the HD mutation but have not yet developed symptoms.

2015 will see the start of the first human clinical trial of a gene silencing or huntingtin - lowering drug, which specifically aims to reduce production of mutant huntingtin in the brains of HD patients.

Not exact matches

In humans, Huntington's is an inherited disease caused by a gene encoding a toxic protein, called mutant huntingtin, which causes brain cells to die.

In a nonhuman primate model geneticist Anthony Chan DVM, PhD, and his colleagues at Yerkes developed, rhesus macaques carry a gene encoding a fragment of mutant human huntingtin.

University of California, Irvine neurobiologists Leslie Thompson and Joseph Ochaba with the Departments of Neurobiology & Behavior and Psychiatry & Human Behavior and their colleagues from UCI and from Children's Hospital of Philadelphia have shown that reducing the aberrant accumulation of a particular form of the mutant Huntingtin protein corresponds to improvement in symptoms and neuroinflammation in HD mice.

«The damage caused by the mutant huntingtin protein radiates out through the cell, like a pebble dropped in a pond.

Mochly - Rosen and colleagues identified several other potential biomarkers that were elevated in HD model mice, including the levels of 8 - hydroxy - deoxy - guanosine, a product of oxidative DNA damage, in the urine and the presence of mutant huntingtin aggregates and oxidative damage in muscle and skin cells.

«Because mitochondrial dysfunction has been proposed to play an important role in the pathogenesis of Huntington's disease,» said Qi, «we investigated the binding proteins of mutant huntingtin on mitochondria.»

The study successfully countered harmful effects of mutant huntingtin and protected nerve cells in several models of Huntington's disease.

In March Chris Ross and his colleagues reported that cells bearing mutant huntingtin could survive if they produced extra CBP.

Being able to detect and measure the amount of mutant huntingtin present in the nervous system will be a valuable way of seeing whether the gene - silencing drug is hitting its target and has the intended effect, lowering the amount of disease causing mHTT protein.

In July, Elena Cattaneo and her colleagues at the University of Milan reported that mutant huntingtin affects another key neuron - survival protein called brain - derived neurotrophic factor (BDNF).

What's more, the concentration of mutant huntingtin predicted the severity of movement and cognitive problems in patients.

The mutant Huntingtin gene is thought to cause toxic levels of protein to aggregate in the brain.

Next, Grima looked at cell death in cultured neurons with a healthy or a mutant form of Huntingtin, or with a mutant form of Huntingtin that was treated with small amounts of an experimental drug called KPT - 350, one that prevents a nuclear export protein, Exportin - 1, from shuttling proteins and RNA out of the nucleus.

Blocking nuclear export seemed to prevent cells from dying and counteracted the defects in neurons with mutant Huntingtin, the researchers say.

To further explore nuclear transport's role in Huntington's disease, Grima took lab - grown mouse neurons and used chemical switches to a) turn on both an additional healthy copy of the RanGAP1 gene and a mutant version of Huntingtin; b) just turn on the mutant Huntingtin; or c) just turn on a healthy version of Huntingtin.

When caspases chopped off small peptides from the mutant region of huntingtin, they thought, the peptides accumulated into the abnormal globs seen in the neurons of Huntington's victims.

Juliette Gafni, Theodora Papanikolaou, Francesco DeGiacomo, Jennifer Holcomb, Sylvia Chen, Menalled L.; Kudwa A.; Jon Fitzpatrick, Miller S.; Ramboz S.; Pasi Tuunanen, Kimmo Lehtimaki, Xiangdong William Yang, Seung Kwak, Larry Park, David Howland, Hyunsun Park, and Lisa Ellerby Caspase - 6 activity in a BAC HD mouse modulates steady state levels of mutant huntingtin protein but is not necessary for production of a 586 amino acid proteolytic fragment.

Showed that the nucleus is a critical subcellular site in which mutant huntingtin induces neurodegeneration.

Clumps of mutant huntingtin protein in brain cells are a hallmark of HD, and they build up slowly, occupying more and more cells over time.

Activity of the mutant huntingtin gene was reduced by around 50 % in the brain near the injection site.

While everyone agrees that the mutant huntingtin protein is the main cause of harm in Huntington's disease, some researchers think that huntingtin RNA could be an additional source of damage.

Cytotoxicity of a mutant huntingtin fragment in yeast involves early alterations in mitochondrial OXPHOS complexes II and III.

When a person has too many CAGs in a row near the start of the huntingtin gene, a harmful «mutant» form of the protein is produced based on the instructions in the gene.

S - Nitrosylation of Drp1 Mediates Mutant Huntingtin - Induced Mitochondrial Fragmentation and Neuronal Injury in Huntington's Disease.

In this study, we employed a method called optical pulse - labeling, or OPL, which allowed us to see how the mutant huntingtin ravaged the brain over time — neuron by neuron.»

There are many ways of achieving the goal of lowering mutant huntingtin, expected to start new trials soon or already in early trials.

«Huntington's — an inherited and fatal disorder that leads to problems with muscle coordination, cognition and personality — is characterized by the toxic buildup of a mutant form of the huntingtin protein in the brain,» explained Dr. Finkbeiner, who directs the Taube - Koret Center for Neurodegenerative Disease Research at Gladstone.

Plus, there are other drugs being developed and tested that aim to slow or prevent HD in other ways, by helping restore normal functioning of the brain in the presence of the mutant huntingtin protein.

Surprisingly, the research team noticed clear differences in the ability of different types of neurons to clear mutant huntingtin.

Emphasising their desire to move the drug forward, in a separate announcement made directly to the HD community, Ionis said «Upon study completion, the next step for this program will be to conduct a study to investigate if decreasing mutant huntingtin protein with IONIS - HTTRx can slow the progression of this terrible disease.»

We hope this will allow WAVE to actually measure what they're trying to do, which is to reduce the levels of the mutant huntingtin protein in the brain.

That's not what we expect when patients are given huntingtin - lowering drugs, which might produce around 50 - 75 % reductions in the mutant and healthy protein.

We know that lowering the level of mutant huntingtin protein in HD mouse models significantly improves symptoms reminiscent of HD, providing hope that similar treatments in people may be effective.

If we could do it in people, it'd mean that extra-long or «mutant» huntingtin would never even have a chance to make neurons sick.

The huntingtin protein, which in its mutant form causes Huntington's disease, is difficult to study because it forms clumps rather than neat crystals.

Gafni J, Papanikolaou T, DeGiacomo F, Holcomb J, Chen S, Menalled L, Kudwa A, Fitzpatrick J, Miller S, Ramboz S, Tuunanen P, Lehtimaki K, William YX, Kwak S, Park L, Howland D, Park H, Ellerby L.Caspase - 6 activity in a BACHD mouse modulates steady - state levels of mutant huntingtin protein but is not necessary for production of a 586 amino acid proteolytic fragment.

In HD, scientists know that the mutant huntingtin protein builds up in cellIn HD, scientists know that the mutant huntingtin protein builds up in cellin cells.

For example, if we block mutant huntingtin production in cells or animals with «gene silencing» techniques, how can we confirm that this treatment actually does what it's supposed to do in the brains of patients with HD?

The 120 repeat R6 / 2 mouse model of HD expresses a human transgene containing exon 1 of the mutant huntingtin gene and faithfully replicates many of the symptoms of the disease, including progressive loss of body weight, marked impairments in cognition, and severe motor deficits.

Project Title: In vivo genome - wide genetic screening for modifiers of mutant Huntingtin toxicity