MedWorm: Huntington's Disease

Late-onset Huntington disease with intermediate CAG repeats: true or false?

Journal of Neurology, Neurosurgery & Psychiatry — Tue, 09 Feb 2010 15:00:05 +0100

Huntington disease (HD) is a neurodegenerative disorder associated with an expanded CAG trinucleotide repeat length in the huntingtin gene. ‘Intermediate alleles’ with 27 to 35 CAG repeats generally do not cause HD but are unstable upon germ-line transmission. Insights in CAG repeat mosaicism and enhanced trinucleotide expansion in postmitotic neurons indicate that in the intermediate range, other factors than the CAG repeat length in diagnostic tests have to be considered. Here, we report two patients with mild, late onset HD and an intermediate repeat allele. The authors anticipate that intermediate repeats can cause late-onset HD due to disease modifiers and may be more common than previously stated. (Source: Journal of Neurology, Neurosurgery & Psychiatry)

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Huntington Drug Produces Slight Benefit (CME/CE)

MedPage Today Neurology — Tue, 09 Feb 2010 13:43:08 +0100

An investigational drug that protects mitochondria in nerve cells helped restore some cognitive function in patients with Huntington's disease, researchers said. (Source: MedPage Today Neurology)

Health News of the Day

Clinical Cases and Images — Tue, 09 Feb 2010 13:01:00 +0100

is a daily summary made from the selected links I post on Twitter. It is in bullet-point format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day: Spending on health care in US is 17.3% of GDP, up from 16.2% in 2008 - largest percentage increase in 5 decades http://goo.gl/IZE4 People who drank 2 or more soft drinks a week had an 87% increased risk of pancreatic cancer http://goo.gl/DcXd Thirdhand Smoke (tobacco smoke residue) Creates Indoor Cancer Risk. Nicotine reacts with indoor air pollutant to form carcinogenic compounds called tobacco-specific nitrosamines (TSNAs) http://bit.ly/cRpb4r Mediterranean diet may help prevent dementia - CNN http://bit.ly/a9lGLb Latrepirdine (Dimebon) - oral medication developed for Alzheimer's - may ...

Drug shows promise for Huntington's disease

ScienceDaily Headlines — Tue, 09 Feb 2010 13:00:00 +0100

An early stage clinical trial of the experimental drug dimebon (latrepirdine) in people with Huntington's disease appears to be safe and may improve cognition. (Source: ScienceDaily Headlines)

Drug Shows Promise For Huntington's Disease

Health News from Medical News Today — Tue, 09 Feb 2010 10:00:00 +0100

An early stage clinical trial of the experimental drug dimebon (latrepirdine) in people with Huntington's disease appears to be safe and may improve cognition. That is the conclusion of a study published in the Archives of Neurology. "This is the first clinical trial that has focused on what is perhaps the most disabling aspect of the disease," said University of Rochester Medical Center neurologist Karl Kieburtz, M.D., the lead author of the study... (Source: Health News from Medical News Today)

Drug Shows Promise For Huntington's Disease

Alzheimer's / Dementia News From Medical News Today — Tue, 09 Feb 2010 10:00:00 +0100

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Medication Appears Well Tolerated And May Have Beneficial Effects In Patients With Huntington's Disease

Health News from Medical News Today — Tue, 09 Feb 2010 09:00:00 +0100

A medication previously studied in patients with Alzheimer's disease (latrepirdine) appears well tolerated and may improve thinking, learning and memory skills among individuals with Huntington's disease, according to a report in the February issue of Archives of Neurology, one of the JAMA/Archives journals. "Huntington's disease is a hereditary neurodegenerative disorder that affects movement, behavior and cognition and leads to death within 20 years of disease onset," the authors write as background information in the article... (Source: Health News from Medical News Today)

Medication Appears Well Tolerated And May Have Beneficial Effects In Patients With Huntington's Disease

Huntingtons Disease News From Medical News Today — Tue, 09 Feb 2010 09:00:00 +0100

Alzheimer's drug Dimebon helps Huntington's: study

Reuters: Health — Mon, 08 Feb 2010 22:47:51 +0100

WASHINGTON (Reuters) - Dimebon, a pill being developed for Alzheimer's disease, helped people with Huntington's disease improve their thinking, learning and memory skills, U.S. researchers said on Monday. (Source: Reuters: Health)

Alzheimer's Drug Dimebon Helps Huntington's

MedlinePlus Health News — Mon, 08 Feb 2010 22:47:51 +0100

Dimebon, a pill being developed for Alzheimer's disease, helped people with Huntington's disease improve their thinking, learning and memory skills, U.S. researchers said on Monday. Source: Reuters Health Related MedlinePlus Topics: Alzheimer's Disease, Huntington's Disease (Source: MedlinePlus Health News)

A Randomized, Placebo-Controlled Trial of Latrepirdine in Huntington Disease [Clinical Trials]

Archives of Neurology — Mon, 08 Feb 2010 20:51:01 +0100

Conclusions Short-term administration of latrepirdine is well tolerated in patients with HD and may have a beneficial effect on cognition. Further investigation of latrepirdine is warranted in this population with HD. Trial Registration clinicaltrials.gov Identifier: NCT00497159 (Source: Archives of Neurology)

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New Data Point To Huntington's Disease Hope

NPR Health and Science — Mon, 08 Feb 2010 20:00:00 +0100

A study being published Monday offers hope for those with Huntington's disease. The Archives of Neurology has a report about a drug aimed at the serious cognitive deficits that people with Huntington's also suffer.» E-Mail This » Add to Del.icio.us (Source: NPR Health and Science)

Drug shows promise for Huntington's disease

EurekAlert! - Medicine and Health — Mon, 08 Feb 2010 05:00:00 +0100

(University of Rochester Medical Center) An early stage clinical trial of the experimental drug dimebon (latrepirdine) in people with Huntington's disease appears to be safe and may improve cognition. That is the conclusion of a study published today in the Archives of Neurology. (Source: EurekAlert! - Medicine and Health)

Medication appears well-tolerated, beneficial in Huntington's disease patients

EurekAlert! - Medicine and Health — Mon, 08 Feb 2010 05:00:00 +0100

(JAMA and Archives Journals) A medication previously studied in patients with Alzheimer's disease (latrepirdine) appears well tolerated and may improve thinking, learning and memory skills among individuals with Huntington's disease, according to a report in the February issue of Archives of Neurology, one of the JAMA/Archives journals. (Source: EurekAlert! - Medicine and Health)

Identification of novel 1,4-benzoxazine compounds that are protective in tissue culture and in vivo models of neurodegeneration

Journal of Neuroscience Research — Mon, 08 Feb 2010 00:00:00 +0100

We report that several 2-arylidine and 2-hetarylidin derivatives of the 1,4-benzoxazines class of compounds are highly protective in tissue culture models of neurodegeneration. Results obtained using pharmcalogical inhibitors indicate that neuroprotection by these compounds does not involve the Raf-MEK-ERK or PI-3 kinase-Akt signaling pathways nor other survival-promoting molecules such as protein kinase A (PKA), calcium calmodulin kinase A (CaMK), and histone deacetylases (HDACs). We tested one of these compounds, (Z)-6-amino-2-(3[prime],5[prime]-dibromo-4[prime]-hydroxybenzylidene)-2H-benzo[b][1,4]oxazin-3(4H)-one, designated as HSB-13, in the 3-nitropropionic acid (3-NP)-induced mouse model of Huntington's disease. HSB-13 reduced striatal degeneration and improved behavioral performance...

Directed Evolution Reveals Hidden Properties of VMAT, a Neurotransmitter Transporter [Membrane Biology]

Journal of Biological Chemistry — Fri, 05 Feb 2010 14:38:44 +0100

The vesicular neurotransmitter transporter VMAT2 is responsible for the transport of monoamines into synaptic and storage vesicles. VMAT2 is the target of many psychoactive drugs and is essential for proper neurotransmission and survival. Here we describe a new expression system in Saccharomyces cerevisiae that takes advantage of the polyspecificity of VMAT2. Expression of rVMAT2 confers resistance to acriflavine and to the parkinsonian toxin 1-methyl-4-phenylpyridinium (MPP+) by their removal into the yeast vacuole. This expression system allowed identification of a new substrate, acriflavine, and isolation of mutants with modified affinity to tetrabenazine (TBZ), a non-competitive inhibitor of VMAT2 that is used in the treatment of various movement disorders including Tourette syndrome a...

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Deletion of the Huntingtin Polyglutamine Stretch Enhances Neuronal Autophagy and Longevity in Mice

PLoS Genetics — Fri, 05 Feb 2010 00:00:00 +0100

Author Summary Expansion of a stretch of glutamines near the amino-terminus of huntingtin (htt), the protein product of the IT15 gene, is a deleterious mutation that causes Huntington's disease (HD). Here we show, in contrast, that deletion of htt's normal polyglutamine stretch (ΔQ-htt) is a potentially beneficial mutation that can ameliorate HD mouse model phenotypes when ΔQ-htt is expressed together with a version of htt with the HD mutation. In addition, ΔQ-htt expression can enhance longevity when expressed in either an HD mouse model or in non–HD mice. ΔQ-htt's effects on both lifespan and HD model phenotypes are likely due to an increase in autophagy, a major recycling pathway in cells that is involved in the turnover of cellular components, and aggregated protein. Based on ou...

Monkey hybrid stem cells develop cellular features of Huntington's disease

BMC Cell Biology - Latest articles — Fri, 05 Feb 2010 00:00:00 +0100

Conclusions: Huntington's disease cellular features is influenced by neural developmental events.These results are the first to demonstrate that a pluripotent stem cell line is able to mimic Huntington's disease progression that parallels neural development, which could be a useful cell model for investigating the developmental impact on Huntington's disease pathogenesis. (Source: BMC Cell Biology - Latest articles)

Top-Line Phase 3 Results Positive for Pridopidine in Huntington's

Medscape Med Students Headlines — Thu, 04 Feb 2010 13:53:15 +0100

The dopaminergic stabilizer appears to improve motor function with an adverse event profile, the manufacturers say, similar to placebo. Medscape Medical News (Source: Medscape Med Students Headlines)

Positive top-line results announced from phase III study of pridopidine (Huntexil®) in Huntington's disease

NeLM - News — Thu, 04 Feb 2010 00:00:00 +0100

Source: BioSpace Area: News Positive top-line results have been announced from the MermaiHD study, a European phase III study of pridopidine (Huntexil®) for Huntington's disease (n= 437). Six months treatment with 45mg twice daily demonstrated statistically and clinically significant improvements compared to placebo in measures of motor symptoms, the primary endpoint. Treatment with 45mg once daily showed some improvements on motor function domains, but did not reach statistical significance. Treatment was reported to be generally very well tolerated with an adverse event profile similar to placebo, and there was no associated worsening of signs and symptoms of the disease. Patients who completed the six months' randomised study treatment have been offered the option of open-label treatm...

Three Brain Diseases Linked to Same Neural Protein

Medicineworld.org: New Article Alert — Wed, 03 Feb 2010 14:04:47 +0100

For the first time, scientists from the University of Pennsylvania School of Medicine have observed that three different degenerative brain disorders are linked by a toxic form of the same protein. The protein, called Elk-1, was found in clumps of misshaped proteins that are the hallmarks of Parkinson's disease, Alzheimer's disease, and Huntington's disease........ (Source: Medicineworld.org: New Article Alert)

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Three Brain Diseases Linked By Toxic Form Of Same Neural Protein

Health News from Medical News Today — Wed, 03 Feb 2010 10:00:00 +0100

For the first time, researchers from the University of Pennsylvania School of Medicine have found that three different degenerative brain disorders are linked by a toxic form of the same protein. The protein, called Elk-1, was found in clumps of misshaped proteins that are the hallmarks of Parkinson's disease, Alzheimer's disease, and Huntington's disease... (Source: Health News from Medical News Today)

Three Brain Diseases Linked By Toxic Form Of Same Neural Protein

Biology / Biochemistry News From Medical News Today — Wed, 03 Feb 2010 10:00:00 +0100

Early Detection of Huntington's Disease

Medscape Neurology & Neurosurgery Headlines — Tue, 02 Feb 2010 17:00:00 +0100

Huntington's disease is a devastating illness, although its autosomal-dominant genetic transmission allows a unique opportunity to study apparently healthy individuals before manifest disease. Future Neurology (Source: Medscape Neurology & Neurosurgery Headlines)

3 brain diseases linked by toxic form of same neural protein

EurekAlert! - Medicine and Health — Tue, 02 Feb 2010 05:00:00 +0100

(University of Pennsylvania School of Medicine) Researchers have found that three different degenerative brain disorders are linked by a toxic form of the same protein. Elk-1 was found in clumps of misshaped proteins that are the hallmarks of Parkinson's disease, Alzheimer's disease, and Huntington's disease. This suggests a molecular link between the presence of inclusions and neuronal loss that is shared across a spectrum of neurodegenerative disease. Identifying these links could open up novel avenues for therapeutic intervention. (Source: EurekAlert! - Medicine and Health)

Discovery of mechanism in brain cell injury in Huntington's offers new treatment approaches

ScienceDaily Headlines — Mon, 01 Feb 2010 13:00:00 +0100

Scientists have uncovered a key cellular mechanism that alters brain cell function in Huntington's disease, and identified a possible treatment for the disease. (Source: ScienceDaily Headlines)

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Multifactorial Intervention to Reduce Cardiovascular Events in Type 2 Diabetes

Current Diabetes Reports — Mon, 01 Feb 2010 06:48:04 +0100

Abstract Type 2 diabetes is associated with a significantly increased risk of cardiovascular disease (CVD) morbidity and mortality. Although several clinical trials have evaluated the effects of interventions to reduce CVD risk in people with diabetes, such studies are primarily conducted to target individual risk factors such as hypertension, hyperglycemia, and dyslipidemia rather than using a multifactorial interventional approach. Existing clinical trial data suggest that intensive multifactorial interventions that target several important risk factors simultaneously result in a significantly greater risk reduction in CVD risk compared with single risk factor interventions. However, few studies have evaluated the efficacy and effectiveness of such interventions on CVD h...

Huntington adds international fund

bizjournals.com Health Care:Health Insurance headlines — Mon, 01 Feb 2010 05:00:00 +0100

Huntington Asset Advisors has launched a second international equity mutual fund. (Source: bizjournals.com Health Care:Health Insurance headlines)

Notice of Intent to Publish a Program Announcement for Research Grant Applications Supporting Validation of Novel Therapeutic Targets for Huntingtons Disease (R01)

NIH Funding Opportunities (Notices, PA, RFA) — Fri, 29 Jan 2010 17:00:00 +0100

Notice from the NIH Guide for Grants and Contracts (Source: NIH Funding Opportunities (Notices, PA, RFA))

Can Neurodegenerative Diseases be Cured by Chaperone Induction?

About.com Biotech Biomedical — Fri, 29 Jan 2010 00:00:00 +0100

Several neurodegenerative diseases, such as Parkinson's and Huntington's have been linked to the misfolding of proteins. The improper folding might not only reduce the specific activity of the protein, but may cause them to actually become neurotoxic. Research groups like Neef et al. have theorized that these diseases might be stopped in their tracks if protein folding could be improved. One of the transcription factors involved in protein folding, Heat Shock Transcription Factor 1 (HSF1), a critical regulator of chaperone production, has been found to be poorly processed in neurons, meaning the active form is not efficiently made. Neef et al. set out to fix this by finding a small molecule that could induce proper HSF1 formation and promote chaperone expression, first in yeast, then rat n...

Huntington's Disease: Discovery Of Mechanism In Brain Cell Injury Offers New Treatment Approaches

Health News from Medical News Today — Thu, 28 Jan 2010 13:00:00 +0100

Scientists at the Brain Research Centre and Centre for Molecular Medicine and Therapeutics have uncovered a key cellular mechanism that alters brain cell function in Huntington's disease, and identified a possible treatment for the disease. The results of the study were published online today and will appear in the January 28 edition of the journal Neuron. Huntington's disease is an inherited degenerative brain disease that causes cognitive and motor impairment, and eventually death. One in 10,000 Canadians suffers from Huntington's disease... (Source: Health News from Medical News Today)

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Huntington's Disease: Discovery Of Mechanism In Brain Cell Injury Offers New Treatment Approaches

Neurology / Neuroscience News From Medical News Today — Thu, 28 Jan 2010 13:00:00 +0100

Scientists at the Brain Research Centre and Centre for Molecular Medicine and Therapeutics have uncovered a key cellular mechanism that alters brain cell function in Huntington's disease, and identified a possible treatment for the disease. The results of the study were published online today and will appear in the January 28 edition of the journal Neuron... (Source: Neurology / Neuroscience News From Medical News Today)

Mitochondrial haplogroup H correlates with ATP levels and age at onset in Huntington disease

Journal of Molecular Medicine — Thu, 28 Jan 2010 07:04:20 +0100

Abstract Mitochondrial dysfunction has been implicated in the pathogenesis of Huntington disease (HD), a primarily neurodegenerative disorder that results from an expansion in the polymorphic trinucleotide CAG tract in the HD gene. In order to evaluate whether mitochondrial DNA (mtDNA) variation contributes to HD phenotype we genotyped 13 single nucleotide polymorphisms (SNPs) that define the major European mtDNA haplogroups in 404 HD patients. Genotype-dependent functional effects on intracellular ATP concentrations were assessed in peripheral leukocytes. In patients carrying the most common haplogroup H (48.3%), we demonstrate a significantly lower age at onset (AO). In combination with PGC-1alpha genotypes, 3.8% additional residual variance in HD AO can be explained. Intr...

Discovery of mechanism in brain cell injury in Huntington's offers new treatment approaches

EurekAlert! - Medicine and Health — Wed, 27 Jan 2010 05:00:00 +0100

(University of British Columbia) Scientists at the Brain Research Centre and Centre for Molecular Medicine and Therapeutics have uncovered a key cellular mechanism that alters brain cell function in Huntington's disease, and identified a possible treatment for the disease. (Source: EurekAlert! - Medicine and Health)

The Montreal Cognitive Assessment as a screening tool for cognitive dysfunction in Huntington's disease

Movement Disorders — Wed, 27 Jan 2010 00:00:00 +0100

In this study, we compare the MoCA with the mini-mental state examination (MMSE) as a screening tool for cognitive dysfunction among 53 patients with HD. The mean MMSE score was 26 ± 2.4, and mean MoCA score was 21 ± 4.4. Twenty-one patients (81%) of those who scored [ge]26 on the MMSE had the MoCA score (Source: Movement Disorders)

Legal settlements seen as ripe business for Huntington

bizjournals.com Health Care:Health Insurance headlines — Mon, 25 Jan 2010 05:00:00 +0100

Huntington Bancshares Inc. is looking to tap into the hundreds of millions of dollars in legal settlement payments that change hands every year. (Source: bizjournals.com Health Care:Health Insurance headlines)

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Protective Effect of Sesamol against 3-Nitropropionic Acid-Induced Cognitive Dysfunction and Altered Glutathione Redox Balance in Rats

Basic and Clinical Pharmacology and Toxicology — Mon, 25 Jan 2010 00:00:00 +0100

Abstract: Sesamol (SML) (Sesamum indicum, Linn, Pedaliaceae) has been used traditionally as a health supplement in India and other countries for a long time. It is a well-known antioxidant, currently being tried against several neurological disorders. The present study was designed to evaluate the potential of sesamol treatment against 3-nitropropionic acid (3-NP)-induced cognitive impairment and oxidative damage in striatal, cortex and hippocampal regions of the rat. The memory performance was assessed by Morris water maze and elevated plus maze paradigms. The oxidative damage was assessed by estimating the total glutathione, reduced glutathione, oxidized glutathione levels and glutathione redox ratio. Glutathione-S-transferase and lactate dehydrogenase enzymes were also measured in diffe...

Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB and BDNF.

Neurobiology of Disease — Mon, 25 Jan 2010 00:00:00 +0100

In this study we tested whether phosphodiesterase 5 (PDE5) inhibitors, sildenafil and vardenafil, would afford protection against 3-nitropropionic acid (3NP), which produces striatal lesions that closely mimic some of the neuropathological features of Huntington's Disease (HD). The neurotoxin was given over 5 days by constant systemic infusion using osmotic minipumps. Animals treated with PDE5 inhibitors (sildenafil or vardenafil) showed improved neurologic scores, reduced the loss of striatal DARPP-32 protein levels and lesion volumes and decreased calpain activation produced by 3NP. This protective effect was independent of changes in 3NP-induced succinate dehydrogenase inhibition. Furthermore, striatal p-CREB levels along with the expression of BDNF were significantly increased in silde...

New Gene Involved In Autophagy, The Cellular Recycling Programme, Identified By Researchers

Huntingtons Disease News From Medical News Today — Sat, 23 Jan 2010 08:00:00 +0100

All cells are equipped with a recycling programme to collect and remove unnecessary cellular components. Autophagy sequesters and digests aged organelles, damaged proteins and other components, which, if not disintegrated and recycled, threaten cell viability... (Source: Huntingtons Disease News From Medical News Today)

Huntington Bank red ink mounts in 4Q

bizjournals.com Health Care:Pharmaceuticals headlines — Fri, 22 Jan 2010 14:08:44 +0100

Continued building of reserves against troubled loans pushed Huntington Bancshares Inc. to another loss in the fourth quarter, but the bank told investors Friday it could post a quarterly profit this year if economic conditions don’t deteriorate. (HBAN) (Source: bizjournals.com Health Care:Pharmaceuticals headlines)

Compounds that help protect nerve cells discovered

ScienceDaily Headlines — Thu, 21 Jan 2010 13:00:00 +0100

Scientists have found some compounds that improve a cell's ability to properly "fold" proteins and could lead to promising drugs for degenerative nerve diseases, including Huntington's disease, Alzheimer's disease and Parkinson's disease. (Source: ScienceDaily Headlines)

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Alnylam and Collaborators Present Data from Multiple Pre-Clinical and Clinical Programs at RNAi Keystone Symposium

Drugs.com - Clinical Trials — Thu, 21 Jan 2010 12:50:32 +0100

– New Data Include Progress in Delivery, TTR-Mediated Amyloidosis, and Huntington's Disease Programs – – Additionally, Comprehensive Studies Show Superior Performance of “Canonical” siRNAs Compared... (Source: Drugs.com - Clinical Trials)

Discovery Of Compounds That Help Protect Nerve Cells

Health News from Medical News Today — Thu, 21 Jan 2010 08:00:00 +0100

Scientists at Duke University Medical Center have found some compounds that improve a cell's ability to properly "fold" proteins and could lead to promising drugs for degenerative nerve diseases, including Huntington's disease, Alzheimer's disease and Parkinson's disease. Misfolded proteins in nerve cells (neurons) are a common factor in all of these diseases. The Duke team has identified many new chemicals that activate a master regulator to increase the supply of "protein chaperone" molecules that help fold proteins properly... (Source: Health News from Medical News Today)

Discovery Of Compounds That Help Protect Nerve Cells

Alzheimer's / Dementia News From Medical News Today — Thu, 21 Jan 2010 08:00:00 +0100

Scientists at Duke University Medical Center have found some compounds that improve a cell's ability to properly "fold" proteins and could lead to promising drugs for degenerative nerve diseases, including Huntington's disease, Alzheimer's disease and Parkinson's disease. Misfolded proteins in nerve cells (neurons) are a common factor in all of these diseases... (Source: Alzheimer's / Dementia News From Medical News Today)

Alnylam And Collaborators Present Data From Multiple Pre-Clinical And Clinical Programs At RNAi Keystone Symposium

Health News from Medical News Today — Thu, 21 Jan 2010 04:00:00 +0100

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced that it presented data from multiple pre-clinical and clinical programs at the "RNA Silencing: Mechanism, Biology, and Application" Keystone Symposium held January 14-19, 2010 in Keystone, Colorado. Alnylam and its collaborators presented data from Alnylam's therapeutic programs including transthyretin (TTR)-mediated amyloidosis and Huntington's disease, as well as new data on delivery approaches for the systemic delivery of RNAi therapeutics... (Source: Health News from Medical News Today)

Alnylam And Collaborators Present Data From Multiple Pre-Clinical And Clinical Programs At RNAi Keystone Symposium

Huntingtons Disease News From Medical News Today — Thu, 21 Jan 2010 04:00:00 +0100

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Stem Cells: An Overview of the Current Status of Therapies for Central and Peripheral Nervous System Diseases.

Current Medicinal Chemistry — Thu, 21 Jan 2010 00:00:00 +0100

Authors: Orlacchio A, Bernardi G, Orlacchio A, Martino S In regenerative medicine, stem cells are currently considered ideal candidates for the treatment of diseases and injuries of the nervous system, for which, at present, there are no effective treatments. Promising results have been shown by clinical trials for neurodegenerative diseases such as Parkinson's diseases, but also for demyelinising disorders and traumatic lesions of the brain and spinal cord. The proof-of-principle is that the replacement of damaged cells and the restoration of function can be accomplished by the transplantation of embryonic or adult stem cells. Advancements in stem cell biology were recently propelled by the ability to generate induced pluripotent stem (iPS) cells from fibroblasts of several neurodegen...

Induced Pluripotent Stem Cells as a Model for Accelerated Patient- and Disease-specific Drug Discovery.

Current Medicinal Chemistry — Thu, 21 Jan 2010 00:00:00 +0100

Authors: Gunaseeli I, Doss MX, Antzelevitch C, Hescheler J, Sachinidis A Human induced pluripotent stem (iPS) cells hold great promise for therapy of a number of degenerative diseases such as ischemic heart failure, Parkinson's disease, Alzheimer's disease, diabetes mellitus, sickle cell anemia and Huntington disease. They also have the potential to accelerate drug discovery in 3 ways. The first involves the delineation of chemical components for efficient reprogramming of patient's blood cells or cells from biopsies, obviating the need for cellular delivery of reprogramming exogenous transgenes, thereby converting hope into reality for patients suffering from degenerative diseases. Patients worldwide stand to benefit from the clinical applicability of iPS cell-based cell replacement t...

Loss of cannabinoid CB(1) receptor expression in the 6-hydroxydopamine-induced nigrostriatal terminal lesion model of Parkinson's disease in the rat.

Brain Research Bulletin — Thu, 21 Jan 2010 00:00:00 +0100

This study sought to determine if expression of the CB(1) subtype of cannabinoid receptor is altered in the two most commonly-used rat models of Parkinson's disease. Parkinsonian lesions were induced by stereotaxic injection of 6-hydroxydopamine into the axons (medial forebrain bundle) or terminals (striatum) of the nigrostriatal pathway. On days 1, 3, 7, 14 and 28 post-lesion, rats were sacrificed and brains were processed for tyrosine hydroxylase and CB(1) receptor immunohistochemistry. The CB(1) receptor was expressed strongly in the substantia nigra pars reticulata, minimally overlapping with tyrosine hydroxylase immunoreactivity in the pars compacta. Interestingly, while there was little change in CB(1) receptor expression following axonal lesion, expression of the receptor was signif...

Anesthetic management of patients with Huntington disease.

Anesthesia and Analgesia — Wed, 20 Jan 2010 22:22:39 +0100

CONCLUSION: Contrary to previous case reports, we found that patients with HD have normal responses to general anesthesia. However, the anesthesiologist should be aware of interactions between anesthetics and psychiatric medications frequently used by these patients. Measures should also be taken to minimize the risk of pulmonary aspiration because bulbar dysfunction may be a manifestation of this disease. PMID: 20081136 [PubMed - in process] (Source: Anesthesia and Analgesia)

Broadening the therapeutic scope for rapamycin treatment.

Autophagy — Wed, 20 Jan 2010 18:46:12 +0100

Authors: Menzies FM, Rubinsztein DC The role of autophagy in the degradation of aggregate-prone proteins has been well established. As a result, autophagy upregulation has become an attractive therapeutic strategy for the treatment of proteinopathies, a group of diseases caused by the accumulation of mutant misfolded proteins. We have previously shown that rapamycin attenuates the phenotype in a mouse model of Huntington disease when administered pre-symptomatically and have recently extended this to demonstrate the effectiveness of rapamycin in a transgenic mouse model of spinocerebellar ataxia type 3, a polyglutamine disorder caused by mutations in the ataxin-3 gene. Rapamycin, administered from the initial onset of disease signs, improves motor coordination and results in a decrease...

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Comprehension of complex discourse in different stages of Huntington's disease.

International Journal of Language and Communication Disorders — Wed, 20 Jan 2010 00:00:00 +0100

Conclusions & Implications: It is likely that, in complex discourse tasks, individual differences in cognitive capacity may contribute and override other differences related to stage of disease. These results indicate that it is important to assess comprehension even in early stages of Huntington's disease, with tests that are sensitive to subtle language disorders, to reduce communication problems for the individuals concerned and their conversational partners. PMID: 20085535 [PubMed - as supplied by publisher] (Source: International Journal of Language and Communication Disorders)

Huntington beef products recalled

Health News - UPI.com — Tue, 19 Jan 2010 15:43:45 +0100

MONTEBELLO, Calif., Jan. 19 (UPI) -- Huntington Meat Packing Inc., of Montebello, Calif., is recalling about 864,000 pounds of beef that may be tainted with E. coli, inspectors said. (Source: Health News - UPI.com)

Compounds that help protect nerve cells discovered by Duke team

EurekAlert! - Medicine and Health — Tue, 19 Jan 2010 05:00:00 +0100

(Duke University Medical Center) Scientists at Duke University Medical Center have found some compounds that improve a cell's ability to properly "fold" proteins and could lead to promising drugs for degenerative nerve diseases, including Huntington's disease, Alzheimer's disease and Parkinson's disease. (Source: EurekAlert! - Medicine and Health)

Evotec And CHDI Foundation, Inc. Extend Collaboration To Fight Huntington's Disease

Health News from Medical News Today — Sun, 17 Jan 2010 08:00:00 +0100

Evotec AG (Frankfurt Stock Exchange: EVT, TecDAX) announced the extension of its collaboration with CHDI Foundation, Inc. (CHDI) through to the end of 2012. The collaboration, which is aimed at finding new treatments for Huntington's disease and represents one of the largest joint innovation drug discovery CNS alliances within Evotec, will provide Evotec with up to US$ 37.5 million in research funding over the next three years. Evotec has been providing research and innovation support to CHDI since 2006... (Source: Health News from Medical News Today)

Evotec And CHDI Foundation, Inc. Extend Collaboration To Fight Huntington's Disease

Huntingtons Disease News From Medical News Today — Sun, 17 Jan 2010 08:00:00 +0100

Evotec AG (Frankfurt Stock Exchange: EVT, TecDAX) announced the extension of its collaboration with CHDI Foundation, Inc. (CHDI) through to the end of 2012. The collaboration, which is aimed at finding new treatments for Huntington's disease and represents one of the largest joint innovation drug discovery CNS alliances within Evotec, will provide Evotec with up to US$ 37... (Source: Huntingtons Disease News From Medical News Today)

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Alzheimer's disease, Down syndrome and Atherosclerosis Linked

Disabled World — Sat, 16 Jan 2010 01:36:39 +0100

Nearly 20 years ago Huntington Potter kicked up a storm of controversy with the idea that Down syndrome and Alzheimer’s were the same disease. Now the evidence is in: He was right. (Source: Disabled World)

FDA Gives TCA Cellular Therapy Green Light To Proceed With First ALS Adult Stem Cell Trial Using Patient's Own Stem Cells

Health News from Medical News Today — Fri, 15 Jan 2010 03:00:00 +0100

TCA Cellular Therapy, LLC (TCA-CT) announced that the U.S. Food and Drug Administration (FDA) has approved its adult stem cell protocol to conduct Phase I clinical trials to treat Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's disease). This is the second FDA-approved protocol for the treatment of ALS using stem cells in the country; and the first using adult stem cells from the same patient. The aim of the Phase I study will assess safety. ALS afflicts approximately 30,000 Americans. More people die of ALS than Huntington's disease; and the fatalities nearly equal Multiple Sclerosis... (Source: Health News from Medical News Today)

Early defect of transforming growth factor beta-1 formation in Huntington's disease.

J Cell Mol Med — Fri, 15 Jan 2010 00:00:00 +0100

We examined the pharmacological regulation of TGF-beta1 formation in asymptomatic R6/2 mice, where blood TGF-beta1 levels were also reduced. In these R6/2 mice, both the mGlu2/3 metabotropic glutamate receptor agonist, LY379268, and riluzole failed to increase TGF-beta1 formation in the cerebral cortex and corpus striatum, suggesting that a defect in the regulation of TGF-beta1 production is associated with HD. Accordingly, reduced TGF-beta1 mRNA and protein levels were found in cultured astrocytes transfected with mutated exon 1 of the human huntingtin gene, and in striatal knock-in cell lines expressing full-lenght huntingtin with an expanded glutamine repeat. Taken together, our data suggest that plasma TGF-beta1 levels are potential biomarkers of HD development during the asymptomatic ...

Genomic And Personalized Medicine Conference

Genetics News From Medical News Today — Thu, 14 Jan 2010 12:00:00 +0100

Genomic And Personalized Medicine Conference

Health News from Medical News Today — Thu, 14 Jan 2010 12:00:00 +0100

Elsevier have announced the Genomic and Personalized Medicine Conference in Arlington, VA, USA from May 16 -18, 2010, which is supported by The Lancet and organized in association with the book 'Genomic and Personalized Medicine' by Huntington Willard and Geoffrey Ginsburg. The conference will serve the needs of a wide group of stakeholders - practicing physicians, physician-scientists, industry leaders, policy makers, and other health care professionals and trainees at all levels... (Source: Health News from Medical News Today)

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Molecular basis of factor IXa recognition by heparin-activated antithrombin revealed by a 1.7-A structure of the ternary complex [Biochemistry]

Proceedings of the National Academy of Sciences — Tue, 12 Jan 2010 18:26:07 +0100

Factor (f) IXa is a critical enzyme for the formation of stable blood clots, and its deficiency results in hemophilia.... (Source: Proceedings of the National Academy of Sciences)

Mitochondrial-dependent apoptosis in Huntington's disease human cybrids.

Experimental Neurology — Tue, 12 Jan 2010 00:00:00 +0100

Authors: Ferreira IL, Nascimento MV, Ribeiro M, Almeida S, Cardoso SM, Grazina M, Pratas J, Santos MJ, Januário C, Oliveira CR, Rego AC We investigated the involvement of mitochondrial-dependent apoptosis in Huntington's disease (HD) versus control (CTR) cybrids, obtained from the fusion of human platelets with mitochondrial DNA-depleted NT2 cells, and further exposed to 3-nitropropionic acid (3-NP) or staurosporine (STS). Untreated HD cybrids did not exhibit significant modifications in the activity of mitochondrial respiratory chain complexes I-IV or in mtDNA sequence variations suggestive of a primary role in mitochondrial susceptibility in the subpopulation of HD carriers studied. However, a slight decrease in mitochondrial membrane potential and increased formation of intrace...

Elixir Announces First Sirtuin Inhibitor Clinical Trial

Health News from Medical News Today — Mon, 11 Jan 2010 12:00:00 +0100

Elixir Pharmaceuticals, Inc. announced that its partner, Siena Biotech S.p.A., has commenced Phase 1 clinical testing of Elixir's potent, first-in-class SIRT1 (sirtuin-1) inhibitor for the treatment of Huntington's Disease. EX-527, also known as SEN0014196, is currently in a Phase 1a combined single and multiple ascending dose study in the European Union to assess safety, tolerability and pharmacokinetics in healthy volunteers... (Source: Health News from Medical News Today)

Elixir Announces First Sirtuin Inhibitor Clinical Trial

Huntingtons Disease News From Medical News Today — Mon, 11 Jan 2010 12:00:00 +0100

Identification of Phenylbutyrate-Generated Metabolites in Huntington Disease Patients using Parallel LC/EC-array/MS and Off-line Tandem MS.

Analytical Biochemistry — Mon, 11 Jan 2010 00:00:00 +0100

We report here the details of this method and its use for identification of 10 plasma and urinary metabolites in treated subjects, including indole species in urine that are not themselves metabolites of SPB. This approach thus contributes to understanding metabolic pathways that differ among HD individuals being treated with SPB. PMID: 20074541 [PubMed - as supplied by publisher] (Source: Analytical Biochemistry)

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Huntington's disease: tagged for clearance

Nature Medicine — Fri, 08 Jan 2010 14:31:03 +0100

Nature Medicine 16, 32 (2010). doi:10.1038/nm0110-32 Author: Dimitri Krainc The neuronal accumulation of mutant huntingtin is a hallmark of Huntington's disease. New research shows that post-translational modifications of the mutant protein promote its clearance, uncovering new therapeutic targets for this disorder. (Source: Nature Medicine)

AIDS Denialism and Public Health Practice

AIDS and Behavior — Fri, 08 Jan 2010 09:13:24 +0100

Abstract In this paper, we respond to AIDS denialist arguments that HIV does not cause AIDS, that antiretroviral drugs are not useful, and that there is no evidence of large-scale deaths from AIDS, and discuss the key implications of the relationship between AIDS denialism and public health practice. We provide a brief history of how the cause of AIDS was investigated, of how HIV fulfills Koch’s postulates and Sir Bradford Hill’s criteria for causation, and of the inconsistencies in alternatives offered by denialists. We highlight clinical trials as the standard for assessing efficacy of drugs, rather than anecdotal cases or discussions of mechanism of action, and show the unanimous data demonstrating antiretroviral drug efficacy. We then show how statistics on mortali...

Psychogenic chorea associated with family history of Huntington disease

Movement Disorders — Fri, 08 Jan 2010 00:00:00 +0100

No abstract. (Source: Movement Disorders)

The relationship between uric acid levels and Huntington's disease progression

Movement Disorders — Fri, 08 Jan 2010 00:00:00 +0100

Uric acid (UA) may be associated with the progression of Parkinson's disease and related neurodegenerative conditions; however, its association with Huntington's disease (HD) progression has not been explored. A secondary analysis of 347 subjects from the CARE-HD clinical trial was performed to examine the relationship between baseline UA levels and the level of functional decline in HD. Outcomes included change in scores at 30 months for the Unified Huntington's Disease Rating Scale components. There was less worsening of total functional capacity over time with increasing baseline UA levels (adjusted mean worsening in scores: 3.17, 2.99, 2.95, 2.28, 2.21, from lowest to highest UA quintile, P = 0.03). These data suggest a possible association between higher UA levels and slower HD progre...

Modulation of mitochondrial function and morphology by interaction of Omi/HtrA2 with the mitochondrial fusion factor OPA1.

Experimental Cell Research — Fri, 08 Jan 2010 00:00:00 +0100

Authors: Kieper N, Holmström KM, Ciceri D, Fiesel FC, Wolburg H, Ziviani E, Whitworth AJ, Martins LM, Kahle PJ, Krüger R Loss of Omi/HtrA2 function leads to nerve cell loss in mouse models and has been linked to neurodegeneration in Parkinson's and Huntington's disease. Omi/HtrA2 is a serine protease released as a pro-apoptotic factor from the mitochondrial intermembrane space into the cytosol. Under physiological conditions, Omi/HtrA2 is thought to be involved in protection against cellular stress, but the cytological and molecular mechanisms are not clear. Omi/HtrA2 deficiency caused an accumulation of reactive oxygen species and reduced mitochondrial membrane potential. In Omi/HtrA2 knockout mouse embryonic fibroblasts, as well as in Omi/HtrA2 silenced human HeLa cells and...

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Electric Field Propels Worms To Test New Drugs

Health News from Medical News Today — Thu, 07 Jan 2010 09:00:00 +0100

A Nobel-winning process for testing new drugs to treat diseases such as Huntington's, Parkinson's, and muscular dystrophy is getting an electrical charge. Researchers at McMaster University have developed a way to propel and direct microscopic-sized worms (C. elegans nematodes) along a narrow channel using a mild electric field. The discovery opens up significant possibilities for developing high-throughput micro-screening devices for drug discovery and other applications... (Source: Health News from Medical News Today)

Electric Field Propels Worms To Test New Drugs

Medical Devices News From Medical News Today — Thu, 07 Jan 2010 09:00:00 +0100

A Nobel-winning process for testing new drugs to treat diseases such as Huntington's, Parkinson's, and muscular dystrophy is getting an electrical charge. Researchers at McMaster University have developed a way to propel and direct microscopic-sized worms (C. elegans nematodes) along a narrow channel using a mild electric field... (Source: Medical Devices News From Medical News Today)

Birth weight, breast cancer susceptibility loci, and breast cancer risk

Cancer Causes and Control — Wed, 06 Jan 2010 18:06:44 +0100

Conclusions Although our findings require confirmation, we found suggestive evidence that genetic susceptibility modifies the positive association of birth weight with breast cancer. Content Type Journal ArticleCategory Original paperDOI 10.1007/s10552-009-9496-7Authors Rulla M. Tamimi, Harvard School of Public Health Department of Epidemiology 677 Huntington Avenue Boston MA 02115 USAPagona Lagiou, Harvard School of Public Health Department of Epidemiology 677 Huntington Avenue Boston MA 02115 USAKamila Czene, Karolinska Institutet Department of Medical Epidemiology and Biostatistics Box 281 171 77 Stockholm SwedenJianjun Liu, Genome Institute of Singapore Population Genetics Singapore 138672 SingaporeAnders Ekbom, Karolinska Institutet/Karolinska University Hospital ...

Electric field propels worms to test new drugs

ScienceDaily Headlines — Wed, 06 Jan 2010 15:49:54 +0100

Researchers have developed a way to view the effects of a proposed drug treatment in real time using a mild electrical field to stimulate C. elegans nematodes. The discovery opens up significant possibilities for developing high-throughput micro-screening devices for drug discovery and other applications for treating diseases such as Huntington's, Parkinson's and muscular dystrophy. (Source: ScienceDaily Headlines)

Cholesterol homeostasis markers are localized to mouse hippocampal pyramidal and granule layers

Hippocampus — Wed, 06 Jan 2010 00:00:00 +0100

Changes in brain cholesterol homeostasis are associated with multiple diseases, such as Alzheimer's and Huntington's; however, controversy persists as to whether adult neurons produce their own cholesterol, or if it is outsourced to astrocytes. To address this issue, we analyzed 25 genes most immediately involved in cholesterol homeostasis from in situ data provided by the Allen Brain Mouse Atlas. We compared the relative mRNA expression in the pyramidal and granule layers, populated with neurons, with the rest of the hippocampus which is populated with neuronal processes and glia. Comparing the expression of the individual genes to markers for neurons and astrocytes, we found that cholesterol homeostasis genes are preferentially targeted to neuronal layers. Therefore, changes in gene expr...

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DnaK/DnaJ/GrpE of Hsp70 system have differing effects on alpha-synuclein fibrillation involved in Parkinson's disease.

International Journal of Biological Macromolecules — Wed, 06 Jan 2010 00:00:00 +0100

We present for the first time, in vitro characterization of the effect of each component of Hsp70 system on alpha-synuclein (involved in Parkinson's) using SEC and ThT assay. Our results show while some components enhance the aggregation others seem to stabilize alpha-synuclein against aggregation. Keeping whole Hsp70 system intact, the factor responsible for triggering aggregation seemed to be initial alpha-synuclein conformation. PMID: 20060408 [PubMed - as supplied by publisher] (Source: International Journal of Biological Macromolecules)

Electric field propels worms to test new drugs

EurekAlert! - Medicine and Health — Tue, 05 Jan 2010 05:00:00 +0100

(McMaster University) Researchers at McMaster University have developed a way to view the effects of a proposed drug treatment in real time using a mild electrical field to stimulate C. elegans nematodes. The discovery opens up significant possibilities for developing high-throughput micro-screening devices for drug discovery and other applications for treating diseases such as Huntington's, Parkinson's and muscular dystrophy. (Source: EurekAlert! - Medicine and Health)

The influence of cognitive impairment on health-related quality of life in neurological disease

Acta Neuropsychiatrica — Tue, 05 Jan 2010 00:00:00 +0100

Conclusions: We recommend further development of simple tools to screen for cognitive impairments in each neurological condition. We also recommend that a thorough cognitive assessment should be a part of routine clinical practice in those caring for individuals with neurological disorders. (Source: Acta Neuropsychiatrica)

Study Eyes Epileptics' Use of Generic Drugs

Drugs.com - Pharma News — Mon, 04 Jan 2010 14:40:50 +0100

Jan. 4--A blow to her head 20 years ago during a mugging left Thia Moore of Huntington with epilepsy. Until the state began picking up her drug costs, she had been paying $1,200 a month out of pocket for brand-name drugs that kept her... (Source: Drugs.com - Pharma News)

Embryonic stem cell-derived L1 overexpressing neural aggregates enhance recovery in Parkinsonian mice

Brain — Mon, 04 Jan 2010 12:35:23 +0100

Parkinson's disease is the second most common neurodegenerative disease, after Alzheimer's disease, and the most common movement disorder. Drug treatment and deep brain stimulation can ameliorate symptoms, but the progressive degeneration of dopaminergic neurons in the substantia nigra eventually leads to severe motor dysfunction. The transplantation of stem cells has emerged as a promising approach to replace lost neurons in order to restore dopamine levels in the striatum and reactivate functional circuits. We have generated substrate-adherent embryonic stem cell-derived neural aggregates overexpressing the neural cell adhesion molecule L1, because it has shown beneficial functions after central nervous system injury. L1 enhances neurite outgrowth and neuronal migration, differentiation ...

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Small changes in protein chemistry play large role in Huntington's disease

ScienceDaily Headlines — Sun, 03 Jan 2010 10:00:00 +0100

Investigators studying the toxic protein at the root of Huntington's disease have found that small biochemical changes to the protein have a large effect on its toxicity. These changes could be exploited or mimicked to develop a drug treatment for Huntington's. (Source: ScienceDaily Headlines)

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