hdac

Gene expression changes with meditation

With evidence growing that meditation can have beneficial health effects, scientists have sought to understand how these practices physically affect the body.

A new study by researchers in Wisconsin, Spain, and France reports the first evidence of specific molecular changes in the body following a period of mindfulness meditation.

The study investigated the effects of a day of intensive mindfulness practice in a group of experienced meditators, compared to a group of untrained control subjects who engaged in quiet non-meditative activities. After eight hours of mindfulness practice, the meditators showed a range of genetic and molecular differences, including altered levels of gene-regulating machinery and reduced levels of pro-inflammatory genes, which in turn correlated with faster physical recovery from a stressful situation.

“To the best of our knowledge, this is the first paper that shows rapid alterations in gene expression within subjects associated with mindfulness meditation practice,” says study author Richard J. Davidson, founder of the Center for Investigating Healthy Minds and the William James and Vilas Professor of Psychology and Psychiatry at the University of Wisconsin-Madison.

“Most interestingly, the changes were observed in genes that are the current targets of anti-inflammatory and analgesic drugs,” says Perla Kaliman, first author of the article and a researcher at the Institute of Biomedical Research of Barcelona, Spain (IIBB-CSIC-IDIBAPS), where the molecular analyses were conducted.

The study was published in the journal Psychoneuroendocrinology.

Mindfulness-based trainings have shown beneficial effects on inflammatory disorders in prior clinical studies and are endorsed by the American Heart Association as a preventative intervention. The new results provide a possible biological mechanism for therapeutic effects.

The results show a down-regulation of genes that have been implicated in inflammation. The affected genes include the pro-inflammatory genes RIPK2 and COX2 as well as several histone deacetylase (HDAC) genes, which regulate the activity of other genes epigenetically by removing a type of chemical tag. What’s more, the extent to which some of those genes were downregulated was associated with faster cortisol recovery to a social stress test involving an impromptu speech and tasks requiring mental calculations performed in front of an audience and video camera.

Perhaps surprisingly, the researchers say, there was no difference in the tested genes between the two groups of people at the start of the study. The observed effects were seen only in the meditators following mindfulness practice. In addition, several other DNA-modifying genes showed no differences between groups, suggesting that the mindfulness practice specifically affected certain regulatory pathways.

However, it is important to note that the study was not designed to distinguish any effects of long-term meditation training from those of a single day of practice. Instead, the key result is that meditators experienced genetic changes following mindfulness practice that were not seen in the non-meditating group after other quiet activities — an outcome providing proof of principle that mindfulness practice can lead to epigenetic alterations of the genome.

Previous studies in rodents and in people have shown dynamic epigenetic responses to physical stimuli such as stress, diet, or exercise within just a few hours.

“Our genes are quite dynamic in their expression and these results suggest that the calmness of our mind can actually have a potential influence on their expression,” Davidson says.

“The regulation of HDACs and inflammatory pathways may represent some of the mechanisms underlying the therapeutic potential of mindfulness-based interventions,” Kaliman says. “Our findings set the foundation for future studies to further assess meditation strategies for the treatment of chronic inflammatory conditions.”

Danish Scientists On Verge of HIV Cure

Researchers in Denmark are calling a new treatment that could eradicate HIV from infected cells “promising.”

Scientists in Denmark are reporting that they are just months away from unveiling a breakthrough treatment that could functionally cure HIV, reports U.K. newspaper the Telegraph.

The researchers are currently conducting clinical trials of a “novel strategy” that strips the HIV virus from human DNA, allowing the immune system to permanently destroy the virus. The treatment involves releasing the HIV virus from “reservoirs” it forms within DNA, bringing the virus to the surface of the cell. Researchers contend that once the virus has been brought to the cell’s surface, the body’s immune system — boosted by a vaccine — can kill the HIV.

Lead researchers studying the treatment told Telegraph that initial signs are “promising.”

“I am almost certain that we will be successful in releasing the reservoirs of HIV,” said Dr. Ole Søgaard, a senior researcher at Denmark’s Aarhus University Hospital.  “The challenge will be getting the patients’ immune system to recognize the virus and destroy it. This depends on the strength and sensitivity of individual immune systems.”

The Telegraph reports that 15 patients are currently enrolled in clinical trials for the treatment, and if they are successfully cured of HIV, the treatment will be rolled out on a larger scale, administered in combination with an immune-system booster. 

The treatment uses HDAC inhibitors, which are most commonly used to treat cancer, according to theTelegraph. The Danish researchers are experimenting with a particularly potent HDAC inhibitor called Panobinostat. 

The technique has already been proven effective in laboratory trials, including those that use human cells, reports the Telegraph. British scientists are currently researching a similar treatment method, but have yet to advance to the clinical trials stage of the process.

Danish researchers are also optimistic that if these human trials prove effective, the treatment could be made available on a large scale at an affordable cost, providing an alternative to gene therapy, the costly and complex treatment that aims to make a patient’s immune system resistant to HIV. 

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Depoimento de Beatriz Pacheco em “um” dos muitos dias de luta contra a AIDS

Study confirms safety, cancer-targeting ability of nutrient in Study confirms safety, cancer-targeting ability of nutrient in broccoli

Study confirms safety, cancer-targeting ability of nutrient in Study confirms safety, cancer-targeting ability of nutrient in broccoli

Public release date: 9-Jun-2011

External image

English: Broccoli Deutsch: Broccoli (Photo credit: Wikipedia)

CORVALLIS, Ore. – Sulforaphane, one of the primary phytochemicals in broccoli and other cruciferous vegetables that helps them prevent cancer, has been shown for the first time to selectively target and kill cancer cells while leaving normal prostate cells healthy and unaffected.

The findings, made by…

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Hunting the genes in male pattern alopecia: How important are they, how close are we, and what will they tell us?

Abstract

Androgenetic alopecia (AGA) is a highly heritable condition, and the most common form of hair loss in men. The phenotype is characterized by an androgen-dependent, progressive loss of hair from the scalp, which may commence during puberty. Up to 80% of European men experience some degree of androgen-dependent hair loss during their lifetime. Current treatment options for AGA have limited efficacy, and improved understanding of the underlying biological causes is required to facilitate novel therapeutic approaches. To date, molecular genetic studies have implicated 12 genomic regions in AGA, and identified a number of candidate genes. The latter include those encoding the androgen receptor (AR); the histone-deacetylases (HDAC) 4 and 9; and the WNT-molecule WNT10A. However, the majority of contributing genetic risk factors still await identification. This review describes the current status of AGA genetic research. We discuss the strength of the genetic approach and anticipated developments in the field, and how these will facilitate the systematic unravelling of AGA pathobiology, a process which may lead to the identification of new therapeutic targets.

This article is protected by copyright. All rights reserved.

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The safety profile of vorinostat (suberoylanilide hydroxamic acid) in hematologic malignancies: A review of clinical studies.

The safety profile of vorinostat (suberoylanilide hydroxamic acid) in hematologic malignancies: A review of clinical studies.

Cancer Treat Rev. 2016 Feb;43:58-66

Authors: Duvic M, Dimopoulos M

Abstract
Histone acetyltransferases and histone deacetylases (HDACs) are multifunctional enzymes that posttranslationally modify both histone and nonhistone acetylation sites, affecting a broad range of cellular processes (e.g., cell cycle, apoptosis, and protein folding) often dysregulated in cancer. HDAC inhibitors are small molecules that directly interact with HDAC catalytic sites preventing the removal of acetyl groups, thereby counteracting the effects of HDACs. Since the first HDAC inhibitor, valproic acid, was investigated as a potential antitumor agent, there have been a number of other HDAC inhibitors developed to improve efficacy and safety. Despite significant progress in the management of patients with hematologic malignancies, overall survival is still poor. The discovery that HDACs may play a role in hematologic malignancies and preclinical studies showing promising activity with HDAC inhibitors in various tumor types, led to clinical evaluation of HDAC inhibitors as potential treatment options for patients with advanced hematologic malignancies. The Food and Drug Administration has approved two HDAC inhibitors, vorinostat (2006) and romidepsin (2009), for the treatment of cutaneous T-cell lymphoma. This review highlights the safety of HDAC inhibitors currently approved or being investigated for the treatment of hematologic malignancies, with a specific focus on the safety experience with vorinostat in cutaneous T-cell lymphoma.

PMID: 26827693 [PubMed - in process]



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Eisai Acquires Exclusive License from Huya Bioscience International to Develop and Market HDAC Inhibitor HBI-8000 in Japan and Other Asian Countries

TOKYO, Feb 1, 2016 - (JCN Newswire) - Eisai Co., Ltd. announced today that Eisai has entered into an exclusive license agreement with HUYA Bioscience International, LLC (San Diego, CA, USA) to develop and market the oral histone deacetylase (HDAC) inhibitor HBI-8000 in Japan, South Korea, Thailand, Malaysia, Indonesia, Philippines, Vietnam and Singapore.

HBI-8000 is an oral HDAC inhibitor approved in China for use in the treatment of peripheral T-cell lymphoma (PTCL). Non-clinical data suggest HBI-8000 has epigenetic properties that work to regulate tumor cell growth, and the agent is believed to have immunomodulatory properties as well. HBI-8000 is at the clinical stage of testing in Japan as a treatment for PTCL, a type of non-Hodgkin’s lymphoma, under orphan drug designation from the regulatory authority in Japan. Meanwhile, a Phase I clinical study of the agent in solid tumors has been completed in the United States.

Under the agreement, Eisai has exclusive rights to develop and market HBI-8000 in the licensed territories. However, for PTCL and adult T-cell leukemia-lymphoma, HUYA will complete development of the agent for these indications and Eisai will be responsible for commercialization. According to the agreement, Eisai will pay HUYA upfront, development and commercial milestone payments as well as royalties over the term of the license, respectively.

Eisai positions oncology as a key franchise area, and is committed to providing new treatment options for patients with cancer in order to further contribute to addressing unmet medical needs that exist in the treatment of cancer as well as increase the benefits provided to patients and their families.

About HUYA Bioscience International, LLC

HUYA Bioscience International, LLC (United States; President, CEO, Executive Chairman & Founder: Dr. Mireille Gillings) is the leader in enabling and accelerating the global development of novel pharmaceutical product opportunities originating in China. Extensive collaborations are established with Chinese biopharmaceutical, academic and commercial organizations to speed development and value creation in worldwide markets for China-sourced product candidates. With the largest Chinese compound portfolio covering all therapeutic areas, HUYA has emerged as the partner-of-choice for maximizing the value of biopharmaceutical innovation in China. HUYA has offices in the United States, Japan, South Korea and eight strategic locations across China. With the largest team of scientists working with Chinese innovators, HUYA identifies and advances promising drug candidates globally. HUYA received the Asia-Pacific Stevie Award in the Health Products and Services & Pharmaceuticals category and Dr. Mireille Gillings received the Gold Stevie Award in the Woman of the Year 2015 American Business Award category. For more information, please visitwww.huyabio.com

About HBI-8000

HBI-8000 is a member of the benzamide class of histone deacetylase (HDAC) inhibitors designed to block the catalytic pocket of Class I HDACs. HBI-8000 is an orally bioavailable, low-nanomolar inhibitor of cancer-associated HDAC enzymes with favorable pharmacology and safety profiles. HBI-8000 inhibits cancer-associated Class I HDAC1, HDAC2, HDAC3, as well as Class IIb HDAC10 at nanomolar concentrations and stimulates accumulation of acetylated histones H3 and H4 in tumor cells. Studies with human-derived tumor cell lines suggest that HBI-8000 inhibits the growth of many tumor cell lines via multiple mechanisms of action, including epigenetic regulation of tumor cell growth and apoptosis as well as immunomodulatory effects regulating antitumor activity.

To date, HBI-8000 has been dosed in various types of hematological and solid tumors in several clinical trials, including a Phase I trial completed in the United States. HBI-8000 is approved for the treatment of peripheral T-cell lymphoma (PTCL) in China. A Phase I clinical study of the agent in non-Hodgkin’s lymphoma is underway in Japan under orphan drug designation as a treatment for PTCL by the regulatory authority in Japan.

About HDAC

Removing acetyl groups from lysine amino acids on histones to encourage stronger binding of chromatin structures to suppress gene transcription, and adding acetyl groups to weaken binding of chromatin structures to promote transcriptional activity play an important role in regulation of gene transcription on histones. HDAC are enzymes that remove acetyl groups from lysine amino acids on histones, and it is thought that by inhibiting HDAC to allow acetyl groups to accumulate on histones and relax chromatin structures promotes gene transcription activity. In tumor cells, inhibiting HDAC suppresses tumor growth by facilitating the transcriptional activity of cancer suppressing genes and inducing both apoptosis in tumor cells as well as cell cycle arrest.

About Epigenetics

The study of epigenetics involves research into the processes that bring about changes in gene expression without modifying DNA sequencing. It is said that tumor cells have an accumulation of various epigenetic defects in addition to genetic aberrations.

About Eisai

Eisai Co., Ltd. (TSE: 4523; ADR: ESALY) is a research-based human health care (hhc) company that discovers, develops and markets products throughout the world. Eisai focuses its efforts in three therapeutic areas: integrative neuroscience, including neurology and psychiatric medicines; integrative oncology, which encompasses oncotherapy and supportive-care treatments; and vascular/immunological reaction. Through a global network of research facilities, manufacturing sites and marketing subsidiaries, Eisai actively participates in all aspects of the worldwide healthcare system. For more information about Eisai Co., Ltd., please visitwww.eisai.com.

Contact:

Eisai Co., Ltd.
Public Relations Department,
Tokyo, Japan
Tel: +81-3-3817-5120

Copyright 2016 ACN Newswire . All rights reserved.

The cell- and tissue-specific transcription mechanism of the TATA-less syntaxin 1A gene Research Communication

Syntaxin 1A (Stx1a) plays an important role in regulation of neuronal synaptic function. To clarify the mechanism of basic transcriptional regulation and neuron-specific transcription of Stx1a we cloned the Stx1a gene from rat, in which knowledge of the expression profile was accumulated, and elucidated that Stx1a consisting of 10 exons, possesses multiple transcription initiation sites and a 204-bp core promoter region (CPR) essential for transcription in PC12 cells. The TATA-less, conserved, GC-rich CPR has 2 specific protein (SP) sites that bind SP1 and are responsible for 65% of promoter activity. The endogenous CPR, including 23 CpG sites, is not methylated in PC12 cells, which express Stx1a and fetal rat skin keratinocyte (FRSK) cells, which do not, although an exogenous methylated CPR suppresses reporter activity in both lines. Trichostatin A (TSA) and class I histone deacetylase (HDAC) inhibitors, but not 5-azacytidine, induce Stx1a in FRSK cells. Acetylated histone H3 only associates to the CPR in FRSK cells after TSA addition, whereas the high acetylated histone H3–CPR association in PC12 cells was unchanged following treatment. HDAC inhibitor induction of Stx1a was negated by mithramycin A and deletion/mutation of 2 SP sites. HDAC1, HDAC2, and HDAC8 detach from the CPR when treated with TSA in FRSK cells and are associated with the CPR in lungs, and acetylated histone H3 associates to this region in the brain. In the first study characterizing a syntaxin promoter, we show that association of SP1 and acetylated histone H3 to CPR is important for Stx1a transcription and that HDAC1, HDAC2, and HDAC8 decide cell/tissue specificity in a suppressive manner.—Nakayama, T., Mikoshiba, K., Akagawa, K. The cell- and tissue-specific transcription mechanism of the TATA-less syntaxin 1A gene.

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PubMed: Dissecting structure-activity-relationships of crebinostat: Brain penetrant HDAC inhibitors for neuroepigenetic regulation.: Dissecting structure-activity-relationships of crebinostat: Brain penetrant HDAC inhibitors for neuroepigenetic regulation.

Bioorg Med Chem Lett. 2016 Jan 11;

Authors: Ghosh B, Zhao WN, Reis SA, Patnaik D, Fass DM, Tsai LH, Mazitschek R, Haggarty SJ

Abstract
Targeting chromatin-mediated epigenetic regulation has emerged as a potential avenue for developing novel therapeutics for a wide range of central nervous system disorders, including cognitive disorders and depression. Histone deacetylase (HDAC) inhibitors have been pursued as cognitive enhancers that impact the regulation of gene expression and other mechanisms integral to neuroplasticity. Through systematic modification of the structure of crebinostat, a previously discovered cognitive enhancer that affects genes critical to memory and enhances synaptogenesis, combined with biochemical and neuronal cell-based screening, we identified a novel hydroxamate-based HDAC inhibitor, here named neurinostat, with increased potency compared to crebinostat in inducing neuronal histone acetylation. In addition, neurinostat was found to have a pharmacokinetic profile in mouse brain modestly improved over that of crebinostat. This discovery of neurinostat and demonstration of its effects on neuronal HDACs adds to the available pharmacological toolkit for dissecting the molecular and cellular mechanisms of neuroepigenetic regulation in health and disease.

PMID: 26804233 [PubMed - as supplied by publisher] http://dlvr.it/KKdm6Z

The Hereditary Neuropathy Foundation Announces New Partnership with Acetylon Pharmaceuticals to Explore Potential Therapies for Charcot-Marie-Tooth Disease

NEW YORK–(BUSINESSWIRE)–

The Hereditary Neuropathy Foundation (HNF) today announced a new partnership with Acetylon Pharmaceuticals, Inc., a leader in the development of selective histone deacetylase (HDAC) inhibitors for enhanced therapeutic outcomes. As a supplement to HNF’s long-standing collaboration with University of Sheffield, Acetylon will provide an HDAC6 inhibitor compound for testing in a preclinical model of Charcot-Marie-Tooth (CMT), the most common inherited peripheral neuropathy.

To date, HNF has committed $1.5 million to CMT research as part of their Therapeutic Research In Accelerated Discovery (TRIAD) program, which fosters collaboration among academics, government and industry to accelerate potential treatments for CMT. In addition to the Acetylon partnership, HNF will continue to approve expenditures to expedite the search for treatments and cures.

Dr. Andy Grierson, a group leader from the Sheffield Institute for Translational Neuroscience (SITraN) at the University of Sheffield UK, has developed a zebrafish model of CMT2A, the second most common form of CMT, and is using this as a platform to test therapeutic compounds that may lead to potential treatments for CMT patients.

“HNF recognizes the sense of urgency to get treatments to patients and families as quickly as possible,” said Sean Ekins, Chief Science Officer of HNF. “Whenever possible, we try to connect companies with researchers who are pushing the envelope to find potential treatments for CMT. Whether it is a focus on drug development, high throughput screens with FDA approved drugs, or novel compounds that could lead to new targets, we are constantly searching for ways to help accelerate this process.”

“In addition, HNF continues to support the development of their patient-centered programs and clinical trials,” said Allison Moore, Founder and Chief Executive Officer of HNF. “We are committed to expanding our programs to facilitate the long process of therapy development by identifying new endpoints for clinical trials, providing robust patient data, supporting regulatory processes, and completing human trials.”

About Charcot-Marie-Tooth (CMT)

Charcot-Marie-Tooth (CMT) is a progressive disease affecting close to 3 million people worldwide, with early signs including high arched feet, curled toes, and claw-like hands. Many of these signs begin subtly and may go undiagnosed for years, leading to legs and arms becoming deformed and difficult to use. Those with CMT often lose the ability to walk and may become dependent upon assistive devices to remain mobile. Severe, chronic pain is common, and there is no cure. To date, over 80 mutated genes associated with CMT have been identified, with more being discovered each year. The most common form of CMT is CMT1A, for which a treatment is currently being tested in a Phase 3 clinical trial. CMT2A, caused by a mutation in MFN2, is the second most common form of CMT.

About The Hereditary Neuropathy Foundation (HNF)

Hereditary Neuropathy Foundation (HNF) is a non-profit 501©3 organization whose mission is to increase awareness and accurate diagnosis of Charcot-Marie-Tooth disease (CMT) and related inherited neuropathies, support patients and families with critical information to improve quality of life, and support research that will lead to treatments and cures. HNF and partner organization Hannah’s Hope Fund co-sponsor the Global Registry for Inherited Neuropathies (GRIN) to collect clinical and genetic information on patients diagnosed with the various forms of inherited neuropathies in order to advance therapy development for these debilitating disorders. To join the patient registry, visit www.neuropathyreg.org For further information, visit www.hnf-cure.org.

About The Sheffield Institute for Translational Neuroscience (SITraN)

SITraN is a world-leading research center at the University of Sheffield, purpose-built and dedicated to research into neurodegenerative diseases. The state-of-the art research facility was opened in 2010 by HM The Queen and uniquely allows the multidisciplinary collaboration of clinicians, scientists and health professionals to develop new treatments for the benefit of patients.

To find out more visit www.sheffield.ac.uk/sitran/.

About Acetylon

Acetylon Pharmaceuticals, Inc., based in Boston, Massachusetts, is a leader in the development of novel small molecule drugs targeting epigenetic mechanisms for the enhancement of therapeutic outcomes in cancer and other critical human diseases. The Company’s epigenetic drug discovery platform has yielded a proprietary portfolio of optimized, orally-administered Class I and Class II histone deacetylase (HDAC) selective compounds. Alteration of HDAC regulation through selective HDAC inhibition is thought to be applicable to a broad range of diseases including cancer, sickle cell disease and beta-thalassemia, and autoimmune and neurodegenerative diseases. Acetylon’s lead drug candidate, ricolinostat (ACY-1215), is a selective HDAC6 inhibitor currently in Phase 2 clinical development for the treatment of multiple myeloma. In 2013, the Company announced a strategic collaboration agreement with Celgene Corporation, which includes an exclusive option for the future acquisition of Acetylon by Celgene. Acetylon’s scientific founders are affiliated with Harvard University, the Dana-Farber Cancer Institute, the Massachusetts General Hospital, and Harvard Medical School. www.acetylon.com

View source version on businesswire.com: http://www.businesswire.com/news/home/20160126005245/en/

Contact

Hereditary Neuropathy Foundation
Courtney Hollett, 212-722-8396
courtney@hnf-cure.org
or
MacDougall Biomedical Communications on Behalf of Acetylon
Kari Watson, 781-235-3060
kwatson@macbiocom.com

The Hereditary Neuropathy Foundation Announces New Partnership with Acetylon Pharmaceuticals to Explore Potential Therapies for Charcot-Marie-Tooth Disease

NEW YORK–(BUSINESS WIRE)–

The Hereditary Neuropathy Foundation (HNF) today announced a new partnership with Acetylon Pharmaceuticals, Inc., a leader in the development of selective histone deacetylase (HDAC) inhibitors for enhanced therapeutic outcomes. As a supplement to HNF’s long-standing collaboration with University of Sheffield, Acetylon will provide an HDAC6 inhibitor compound for testing in a preclinical model of Charcot-Marie-Tooth (CMT), the most common inherited peripheral neuropathy.

To date, HNF has committed $1.5 million to CMT research as part of their Therapeutic Research In Accelerated Discovery (TRIAD) program, which fosters collaboration among academics, government and industry to accelerate potential treatments for CMT. In addition to the Acetylon partnership, HNF will continue to approve expenditures to expedite the search for treatments and cures.

Dr. Andy Grierson, a group leader from the Sheffield Institute for Translational Neuroscience (SITraN) at the University of Sheffield UK, has developed a zebrafish model of CMT2A, the second most common form of CMT, and is using this as a platform to test therapeutic compounds that may lead to potential treatments for CMT patients.

“HNF recognizes the sense of urgency to get treatments to patients and families as quickly as possible,” said Sean Ekins, Chief Science Officer of HNF. “Whenever possible, we try to connect companies with researchers who are pushing the envelope to find potential treatments for CMT. Whether it is a focus on drug development, high throughput screens with FDA approved drugs, or novel compounds that could lead to new targets, we are constantly searching for ways to help accelerate this process.”

“In addition, HNF continues to support the development of their patient-centered programs and clinical trials,” said Allison Moore, Founder and Chief Executive Officer of HNF. “We are committed to expanding our programs to facilitate the long process of therapy development by identifying new endpoints for clinical trials, providing robust patient data, supporting regulatory processes, and completing human trials.”

About Charcot-Marie-Tooth (CMT)

Charcot-Marie-Tooth (CMT) is a progressive disease affecting close to 3 million people worldwide, with early signs including high arched feet, curled toes, and claw-like hands. Many of these signs begin subtly and may go undiagnosed for years, leading to legs and arms becoming deformed and difficult to use. Those with CMT often lose the ability to walk and may become dependent upon assistive devices to remain mobile. Severe, chronic pain is common, and there is no cure. To date, over 80 mutated genes associated with CMT have been identified, with more being discovered each year. The most common form of CMT is CMT1A, for which a treatment is currently being tested in a Phase 3 clinical trial. CMT2A, caused by a mutation in MFN2, is the second most common form of CMT.

About The Hereditary Neuropathy Foundation (HNF)

Hereditary Neuropathy Foundation (HNF) is a non-profit 501©3 organization whose mission is to increase awareness and accurate diagnosis of Charcot-Marie-Tooth disease (CMT) and related inherited neuropathies, support patients and families with critical information to improve quality of life, and support research that will lead to treatments and cures. HNF and partner organization Hannah’s Hope Fund co-sponsor the Global Registry for Inherited Neuropathies (GRIN) to collect clinical and genetic information on patients diagnosed with the various forms of inherited neuropathies in order to advance therapy development for these debilitating disorders. To join the patient registry, visit www.neuropathyreg.org For further information, visit www.hnf-cure.org.

About The Sheffield Institute for Translational Neuroscience (SITraN)

SITraN is a world-leading research center at the University of Sheffield, purpose-built and dedicated to research into neurodegenerative diseases. The state-of-the art research facility was opened in 2010 by HM The Queen and uniquely allows the multidisciplinary collaboration of clinicians, scientists and health professionals to develop new treatments for the benefit of patients.

To find out more visit www.sheffield.ac.uk/sitran/.

About Acetylon

Acetylon Pharmaceuticals, Inc., based in Boston, Massachusetts, is a leader in the development of novel small molecule drugs targeting epigenetic mechanisms for the enhancement of therapeutic outcomes in cancer and other critical human diseases. The Company’s epigenetic drug discovery platform has yielded a proprietary portfolio of optimized, orally-administered Class I and Class II histone deacetylase (HDAC) selective compounds. Alteration of HDAC regulation through selective HDAC inhibition is thought to be applicable to a broad range of diseases including cancer, sickle cell disease and beta-thalassemia, and autoimmune and neurodegenerative diseases. Acetylon’s lead drug candidate, ricolinostat (ACY-1215), is a selective HDAC6 inhibitor currently in Phase 2 clinical development for the treatment of multiple myeloma. In 2013, the Company announced a strategic collaboration agreement with Celgene Corporation, which includes an exclusive option for the future acquisition of Acetylon by Celgene. Acetylon’s scientific founders are affiliated with Harvard University, the Dana-Farber Cancer Institute, the Massachusetts General Hospital, and Harvard Medical School. www.acetylon.com

View source version on businesswire.com: http://www.businesswire.com/news/home/20160126005245/en/

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Lost in translation? Ten years of development of histone deacetylase inhibitors in acute myeloid leukemia and myelodysplastic syndromes.

Lost in translation? Ten years of development of histone deacetylase inhibitors in acute myeloid leukemia and myelodysplastic syndromes.

Expert Opin Investig Drugs. 2016 Jan 25;

Authors: Stahl M, Gore SD, Vey N, Prebet T

Abstract
INTRODUCTION: Epigenetic changes and mutations in epigenetic modifiers characterize and likely drive many cases of acute myeloid leukemia and myelodysplastic syndrome. Development of DNA methyltransferase inhibitors has been most successful in these diseases. While many epigenetic marks are potential targets of cancer therapies, histone deacetylase inhibitors (HDACi) have undergone the most advanced development to date. Area Covered: In this review, the authors describe and discuss the biology and the clinical results of HDAC inhibitors in the settings of myeloid malignancies. Expert opinion: While significant results have been achieved in lymphoma and myeloma, efficacy remains limited in myeloid malignancies for both single agent and HDACi based combination regimens. The redundancy and the pleiotropic activity of HDACi (on both histone and non-histone proteins) are key factors that have limited to date the selection of patients and the design of robust biomarkers. Recent advances in biology (mechanisms of resistance, immunology) and the design of a more specific third generation of HDACi are two important features that will drive the future clinical development of HDACi in myeloid malignancies.

PMID: 26807602 [PubMed - as supplied by publisher]



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