Published online December 9 in Nature Genetics, the findings describe the GNAL gene, the first primary torsion dystonia gene that directly points to signal transduction pathways in the dopamine system as the origin of pathophysiology. Genetic testing in volunteers from two dystonia families revealed mutations in GNAL. Further screening of 39 additional families identified another six mutations in this gene. This discovery will help development of genetic tests to confirm diagnosis, identify unaffected adult carriers, and provide greater reproductive health options for affected families. The research also unveils a new potential therapeutic target and thus an opportunity for developing new treatments.

“The technique used for the identification of the GNAL gene-called exome sequencing-is a powerful and efficient tool that will accelerate the pace of dystonia gene discovery and, consequently, our understanding of the pathways involved in primary torsion dystonia.” says Laurie Ozelius, PhD, of Mount Sinai School of Medicine, who led the research team. “Any new gene offers the potential to develop new therapeutics, but because GNAL belongs to a well-studied pathway, other components in this pathway may also be targets for drug development” adds Tania Fuchs, PhD, Instructor in the Department of Genetics and Genomic Sciences of Mount Sinai School of Medicine, who is first author of the paper.

Jan Teller, MA, PhD, Science Officer of the DMRF says, “Every time researchers identify a gene, another piece of the puzzle falls into place to clarify our understanding of dystonia. The protein associated with the GNAL gene may hold important clues about how dystonia originates in the brain and potential new strategies for treatment. ”

Primary torsion dystonia is a movement disorder characterized by repetitive twisting muscle contractions and postures that can affect the face, neck, arms, legs, or torso. Common symptoms include tremors, voice problems, or a dragging foot. Primary torsion dystonia may be adult onset or childhood onset. Symptoms can be focal, segmental or generalized. The disorder is dominantly inherited with reduced penetrance, making it difficult to predict which family members may at risk without genetic screening. Three additional genes associated with primary torsion dystonia have been identified: DYT1, THAP1, and CIZI.

Visit The Dystonia Foundation to learn more about their research efforts.

One review of four trials that comprised nearly 9000 participants looked at how well antihypertensive drugs prevent cardiovascular events and death in people with mild hypertension, defined as systolic blood pressure of 140–159 mm Hg or diastolic pressure 90–99 mm Hg (or both). All participants were free of cardiovascular disease at baseline.

No effects were seen over four to five years, compared with placebo, for overall mortality (relative risk 0.85, 95% CI 0.63 to 1.15), coronary heart disease (1.12, 0.80 to 1.57), stroke (0.51, 0.24 to 1.08), or total cardiovascular events (0.97, 0.72 to 1.32). One in 10 people stopped taking antihypertensives because of adverse effects, a fivefold increase over placebo. The review did not report effects of drugs on blood pressure, if any. Another review found two small trials that compared garlic powder with placebo in people with mild hypertension. Garlic might help reduce blood pressure—possibly by about 10 mm Hg for systolic blood pressure and a little less for diastolic blood pressure. However, the confidence intervals were wide, and no data were available on which to assess the potency of garlic to prevent cardiovascular events. Cocoa is rich in flavanols, which cause blood vessel dilatation and are thought to reduce blood pressure. Most of the 20 trials (about 850 participants) tested a daily dose of 500–750 mg of flavanols ingested through chocolate or cocoa products. Most participants were healthy and normotensive at baseline, and most trials lasted only about a month.

Small reductions in blood pressure were seen with cocoa, compared with placebo: −2.77 (−4.72 to −0.82) mm Hg for systolic pressure and −2.20 (−3.46 to −0.93) mm Hg for diastolic blood pressure. One in 20 people allocated cocoa had adverse effects, compared with one in 100 of those receiving placebo. Gastrointestinal effects and a dislike of the product’s taste were the most common problems.

Information sourced from BMJ:

Cochrane Database Syst Rev2012;8:CD006742

Cochrane Database Syst Rev2012;8:CD008893

As calendar winter winds down, the weather can be at its coldest and it is exactly the kind of environment that is not very conducive to good health. Fresh vegetables may not be available as much and the motivation to exercise tends to drop. It is tempting to prepare for winter colds and other health problems, but not all remedies have been able to withstand scientific scrutiny. Dr. Moshe Lewis in a recent article distinguishes between common health supplements that are shown to be health boosters and supplements that don’t quite live up to the hype.

In general there are many obstacles to determine if an herbal product is effective or not. Most patients and physicians are not aware that products available under the same herbal name, for example supplements with the name Echinacea differ considerably in their composition (including different plants, e.g. Echinacea purpurea versus Echinacea angustifolia), use of variable plant parts (e.g. roots versus leaves) extraction methods (e.g. drying versus alcohol extractions) and the addition of other components. These obstacles are also seen in studies testing different things but calling it the same and then generalizing the results.

The survey was conducted by Harris Interactive® on behalf of the Advancing Parkinson’s Trials campaign, sponsored by major Parkinson’s disease and movement disorders groups, including WE MOVE. The survey was funded by The Michael J. Fox Foundation, and was conducted in the United States between January 17, 2005 and March 2, 2005. Five hundred physicians who treat patients with Parkinson’s disease, including 250 neurologists and 250 primary care physicians/gerontologists, responded online, while 518 patients responded via mail. Sampling errors were 5–9%, and samples were not necessarily representative of patients or physicians as a whole.

Results from the survey showed:

• 96% of physicians and 95% of patients agree that clinical trials are necessary to find better treatments for the disease.

• 65% of neurologists and 54% of PCPs/gerontologists have discussed clinical trials with 10% or fewer of their patients with Parkinson’s disease.

• 53% of neurologists and 83% of PCPs/gerontologists have never referred a patient to a clinical trial.

• 11% of patients report that their doctor ever suggested that they participate in a trial.

• Patient awareness of clinical trials comes primarily from support groups (40%) and other people with Parkinson’s disease (27%), rather than their doctors (11%).

• 14% of primary care physicians, 21% of neurologists and 18% of patients surveyed indicated that they are somewhat or very satisfied with the amount of information available about clinical trials for Parkinson’s disease.

• 52% of physicians would not recommend that a patient enroll in a trial if their disease is well-controlled.

• 72% of patients expressed concern about continued access to medication once the trial has stopped.

To learn more about clinical trials visit The Micheal J. Fox website and read Clinical Trials 101. Learn about the facts of clinical trials and how it can help you and others that share medical condition you or your family might have.

If you’re interested in clinical trials going on in your area click on the following links:

Southern California Movement Disorder Specialists Clinical Trials

Neurosearch-USA Clinical Trials

Micheal J. Fox Clinical Trial Finder

Most medications for Parkinson’s disease address the hallmark issue of dopamine deficiency–most specifically the drugs levodopa and carbidopa. However, because treatments do not consistently control PD symptoms, “off time” occurs when the beneficial effects of the drug wear off and symptoms begin to return. While off time in Parkinson’s patients can be difficult to manage, there are improvements in the works. A trial found that levodopa-carbidopa intestinal gel (LCIG) reduced off time by an average of two hours per day when compared to standard oral levodopa-carbidopa.

A key element of the positive results is the mechanism by which this treatment works. “’Off’ time was reduced because the infusion of levodopa-carbidopa intestinal gel (LCIG) helps to deliver levodopa-carbidopa continuously, thereby avoiding the fluctuating levels that occur with standard oral levodopa-carbidopa therapy and that are thought to contribute to the development of wearing off,” said study author C. Warren Olanow, MD, Professor of Neurology and Neuroscience at the Mount Sinai School of Medicine in New York and a Fellow of the American Academy of Neurology.

Recently presented at the American Academy of Neurology’s 64th Annual Meeting in New Orleans, this study offers progress towards improving the quality of life for many PD patients. To read more about it, read the full press release at the American Academy of Neurology.

There are always new treatments for Parkinson’s disease on the horizon and with so many minds working on this, developments are inevitable. A particular drug, dipraglurant, has shown promising results when tested for the treatment of levodopa-induced dyskinesia (PD-LID). The approach is to block a specific glutamate receptor that has previously been linked to excess glutamate activity in those with Parkinson’s disease. A recent trial of 72 patients studied aspects such as safety and the results were reportedly positive. According to a recent press release, “dipraglurant appears to reduce dystonia severity in addition to chorea, the two major LID components.”

Since no drug has yet been approved by the FDA to treat dyskinesia, progress here is welcomed. For more details, see a summary at Addex Therapeutics.

The results are out on a new drug called teriflunomide that has been shown to slow the progression of multiple sclerosis, specifically slowing the time to a first relapse, and has also been approved to treat rheumatoid arthritis. A study, published in the New England Journal of Medicine, (showed) that the drug performed superior to placebo and has a few definite advantages when compared to similar drugs such as fingolimod. According to the lead author isof the study, Paul O’Connor, MD, “it’s safe, and it’s oral, it’s easier to use than fingolimod… and can be washed out of the patient within days — for example, if the patient becomes pregnant,” as opposed to the 45 days fingolimod requires. The drug reduced disease progression by 30 percent and produced no deaths or opportunistic infections.

Its most common side effects include diarrhea, nausea, and hair thinning. There is also some concern about the drug’s interaction with the immune system. Because it inhibits T cell activity, there is a possibility of infection. However, due to the drug’s ability to be washed from the body so quickly, the safety of the drug is improved and as previously mentioned, no infections have yet been observed.

Ultimately it will be beneficial for patients to have more treatment options on the table because everyone’s body reacts differently and this may work better for some than what is currently available. For further reading, visit Neurology Today.

Prior to the decline in cognitive skills that is often the first symptom of Alzheimer’s, it is widely believed that beta-amyloid plaque builds up in the brain. Pfizer Inc has researched a drug, bapineuzumab, that they believe is the best treatment for Alzheimer’s because it is an antibody designed to bind to and clear this plaque from the brain. Bapineuzumab will be used early in the disease process with the aim of slowing Alzheimer’s degenerative effects. Although phase III data had not yet been released, according to Pfizer Inc’s Mikael Dolsten, “this is so far the best chance the industry has for disease modification in Alzheimer’s."

Although these results seem promising, mixed results were observed among patients in smaller, earlier studies such as brain swelling seen in those that received a higher dose. This brain swelling can lead to other effects such as headaches, weakness, memory loss, and hallucinations. In addition to mixed results, the drug may not turn out to be a viable treatment upon further scrutiny because it treats patients that already have developed symptoms and therefore they may have potentially permanent damage inflicted on brain tissue and the neurons themselves.

One study looked at possible trends around amyloid-related imaging abnormalities (ARIA) that seem to be treatment-related:

The authors aimed to investigate the incidence of ARIA during treatment with bapineuzumab. They conducted a systematic, central review of all MRI data from studies (two phase 2 and one ongoing open label) to assess the incidence of ARIA during bapineuzumab treatment, and their associated risk factors and clinical characteristics. The results of the analysis found that ARIA was detected in 36 of 210 (17%) patients treated with bapineuzumab and most cases were clinically silent. The authors conclude, “The increased risk of ARIA among APOE ɛ4 carriers, its association with high bapineuzumab dose, and its timecourse in relation to dosing suggest an association between ARIA and alterations in vascular amyloid burden.” They note that their findings have important implications for elucidation of the mechanisms underlying ARIA and warrant the close monitoring of ARIA in the development of anti-amyloid therapies for Alzheimer’s disease.

Despite these concerns, however, there are indications that the drug may be safer than previously thought:

New longer-term safety data on bapineuzumab suggest that although the brain swelling may be more common than first reported, the risk appears to decline the longer a person is taking the drug. Also, the brain swelling is often mild, causing no symptoms, according to the research presented here at the Alzheimer’s Association International Conference. In animal research and early human studies, bapineuzumab appeared to work just as it was supposed to. But as the side effect of brain swelling surfaced – formerly called vascular edema and now known as amyloid-related imaging abnormalities, or ARIA – so did safety concerns. Encouraging. Dolsten predicts that within the next five years it will be possible for Alzheimer’s patients to receive bapineuzumab treatment, used at earlier stages of the disease for the most beneficial results. Phase III data is expected to be released in the second half of this year.

For further reading, visit The Huffington Post, WebMD, or NELM.

ProteoTech, Inc., a privately held biotechnology company, has entered into a drug development agreement with GlaxoSmithKline R&D Company Limited to collaborate on ProteoTech’s small molecule technology platform against misfolded proteins to specifically advance work on its alpha-synuclein therapeutic program for the treatment of Parkinson’s disease and other synucleinopathies.

Steve Runnels, CEO of ProteoTech, stated “We are pleased to be working with GlaxoSmithKline on the identification and optimization of new therapeutic compounds for Parkinson’s and other synucleinopathies, such as Lewy Body Dementia and Multiple System Atrophy. We are excited to be working with this leading pharmaceutical company on this important project which further validates ProteoTech’s small molecule approach for developing therapies against diseases caused by misfolded proteins.”

Initial support for ProteoTech’s alpha-synuclein therapeutic research program was funded over a four- year period by the Michael J. Fox Foundation for Parkinson’s Research (MJFF). Todd Sherer, PhD, the Chief Executive Officer of the MJFF commented, “We have followed ProteoTech’s success on this therapeutic development program over the years and are extremely pleased to see this collaboration between them and GlaxoSmithKline to accelerate the development of a potential disease modifying treatment for this debilitating disease. This is what we all hoped to see when ProteoTech was initially granted the LEAPS award from our Foundation.”

About ProteoTech: ProteoTech is a private drug development company located in the Seattle, WA area (Kirkland, WA), and is focused on targeting amyloid diseases caused by protein misfolding. Besides the Company’s SynuclereTM program, in late pre-clinical development for the treatment of Parkinson’s disease, ProteoTech is developing Exebryl–1® for the treatment of diseases caused by beta-amyloid protein and tau protein aggregates and fibrils; and is in early human clinical studies with SystebrylTM for the treatment of Systemic AA Amyloidosis. The Company is also in late pre-clinical development for a novel small peptide (PepticlereTM) for the treatment of Alzheimer’s disease beta-amyloid protein aggregates. For more information please see the Company web site at Proteotech.com.

Impax, the Hayward and technology-based generic pharmaceuticals company, in collaboration with GlaxoSmithKline, announced their new treatment for idiopathic Parkinson’s disease on December 21st, 2011. It is currently being reviewed by the U.S. Food and Drug Administration (FDA). Titled “IPX066,” this extended release capsule “is intended to maintain consistent plasma concentration of levodopa for a longer duration versus immediate release levodopa, which may have an impact on fluctuations in clinical response.”

IPX066 has been researched for three and a half years “through multiple clinical studies of efficacy and safety.” IPX066 has been studied in early and advanced U.S. and European Parkinson’s patients.

Caribdopa/levodopa, also known as Sinemet, was one of the first major drugs used to treat Parkinson’s disease and is currently widely used. This drug is converted to dopamine voa a natural enzyme to reduce the symptoms of Parkinson’s disease with less side-effects.

Read this press release at ImpaxLabs.com.

New evidence has been released finding Goteng, a Chinese herb, has healing effects on Parkinson’s Disease patients. The study is strong, and this new evidence could potentially lead to safer and more effective treatments for Parkinson’s Disease. The research team is currently looking for individuals with Parkinson’s Disease who want to participate in future studies.

A pilot clinical study in Hong Kong has found the Chinese herbal medicine Uncaria rhynchophylla (Gouteng), or prescriptions containing Gouteng, to be effective in treating Parkinson’s disease.

Researchers at the Hong Kong Baptist University (HKBU) School of Chinese Medicine, led by Associate Professor Dr. Li Min, have applied for a US patent for this research result, and will soon start the second phase of the clinical study with a US $70,000 research grant from the Food and Health Bureau of the Hong Kong SAR Government.

The researchers identified an active compound Isorhynchophylline (IsoRhy) in the Chinese herb Uncaria rhynchophylla as a potential neuronal autophagy inducer which promoted the clearance of the pathogenic protein alpha-synuclein in the neurons of Parkinson's patients. This unique property of IsoRhy could contribute to the therapeutic action of Uncaria rhynchophylla.

From 2007 to 2009, researchers observed the therapeutic efficacy on 47 patients aged from 50 to 74 years old, who had been suffering from the disease for 18 months to 11 years, and who had been taking the same type of Western medicine. The study revealed that patients who had received the Chinese medicine treatment showed improved communication skills and reduced non-motor symptoms such as depression, anxiety, sleeping difficulties, constipation and poor appetite. In addition, no obvious side effects were found in both groups during the study period.

The department has already begun inviting Parkinson’s disease patients aged between 18 and 80 to participate in a 40-week, second phase clinical research trial.

Read the entire article at AsianScientist.com