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Saturday, January 7, 2012

URINARY DYSFUNCTION IN PARKINSON'S DISEASE

7th January 2012 - New research


Journal of Neurological and Neurosurgical Psychiatry [2011] 82 (12) : 1382-1386 (T.Uchiyama, R.Sakakibara, T.Yamamoto, T.Ito, C.Yamaguchi, Y.Awa, M.Yanagisawa, Y.Higuchi, Y.Sato, T.Ichikawa, T.Yamanishi, T.Hattori, S.Kuwabara)

Urinary dysfunction is common in Parkinson's Disease, but little is known about urinary dysfunction in early and untreated Parkinson's Disease. Nearly two thirds (64%) of people with Parkinson's Disease complain of urinary symptoms. However, there were found to be actual urinary problems in 85% of people with Parkinson's Disease. All of the 64% of people complaining of urinary symptoms had difficulty controlling the retention of urine, or lost control of urinary retention (storage abnormalities). Over a quarter (28%) had difficulty in urinating (voiding difficulties). Over half (58%) had detrusor overactivity. The detrusor muscle is the muscle that contracts when urinating to squeeze out urine. However, whilst urinating, detrusor underactivity rather than overactivity occurred in half of people.

These urinary symptoms were not correlated with gender, severity of Parkinson's Disease, or the type of motor symptom. Urinary dysfunction, manifested primarily as storage abnormalities, and with subclinical voiding difficulties commonly occurs in early and untreated Parkinson's Disease.

Friday, January 6, 2012

New Genetic Mutation Linked to Parkinson's

Using a new, cutting-edge technology for gene sequencing, researchers funded in part by the Parkinson’s Disease Foundation (PDF), have discovered a new gene called vesicular sorting protein complex 35 (VPS35) that is linked to Parkinson’s disease (PD) in people with familial PD. The results appear in the July 14 issue of the American Journal of Human Genetics.
In recent years, researchers have identified about a dozen genes that either cause PD or increase the risk of developing the disease. In general, the motor symptoms of PD begin at a young age in people who have mutations in genes that cause PD. People with mutations in the newly discovered gene, however, were diagnosed with PD around the age of 50.
To search for a new PD gene, an international team of researchers led by Carles Vilariño-Güell, Ph.D., and Matthew J. Farrer, Ph.D., at the University of British Columbia, Vancouver, focused on a family from Switzerland in which 11 people in three generations were diagnosed with PD. They compared the DNA of family members with PD to that of unaffected family members to search for differences that could explain why some developed PD and others did not.
In the past, this type of DNA analysis has been very difficult, requiring examination and DNA collection from large numbers of affected families. The University of British Columbia researchers instead used a new and efficient technique called whole exome sequencing, which focuses on small, but important, sentence-like sections of DNA. These sections govern the production of proteins. Since mutated proteins are most often the cause of genetic diseases, they reasoned that mutations linked to inherited PD would be found here.

Results

  • In all 11 members of the Swiss family who had PD, the scientists identified a mutation in the VPS35 gene.
  • Among 190 additional families that had many cases of PD, the researchers found the same VPS35 mutation in eight members of three families from the United States, Tunisia, and Israel (Yemenite Jews).
  • The VPS35 mutation was found in one person with no family history of PD.
  • The researchers tested DNA samples from more than 3,000 healthy individuals from several countries and found no mutations in VPS35.

What Does it Mean?

Like most other genetic causes of PD, this newly identified genetic mutation is exceedingly rare, resulting in very few cases of PD. However, these rare mutations have helped scientists generate key insights into the disease and a broad understanding of why people may develop PD. This new study is the first to implicate VPS35 in PD. Consequently, these results will need to be replicated in other populations in order to confirm this finding and assess the frequency of this mutation.
Nevertheless, VPS35 is already known to play a role in disease. The gene plays a central role in a neuron’s protein recycling center as part of the so-called retromer system. Breakdowns in the retromer pathway have already been linked to neurodegenerative diseases such as Alzheimer’s and Charcot-Marie-Tooth, the latter is a disease of the peripheral motor and sensory nerves. Therefore, a better understanding of how a VPS35 mutation causes cellular processes to go awry may help scientists unravel the causes of PD and other neurodegenerative diseases.
Reference: Carles Vilariño-Güell, Christian Wider, Owen A. Ross, Justus C. Dachsel, Jennifer M. Kachergus, Sarah J. Lincoln, Alexandra I. Soto-Ortolaza, Stephanie A. Cobb, Greggory J. Wilhoite, Justin A. Bacon, Bahareh Behrouz, Heather L. Melrose, Emna Hentati, Andreas Puschmann, Daniel M. Evans, Elizabeth Conibear, Wyeth W. Wasserman, Jan O. Aasly, Pierre R. Burkhard, Ruth Djaldetti, Joseph Ghika, Faycal Hentati, Anna Krygowska-Wajs, Tim Lynch, Eldad Melamed, Alex Rajput, Ali H. Rajput, Alessandra Solida, Ruey-Meei Wu, Ryan J. Uitti, Zbigniew K. Wszolek, François Vingerhoets, Matthew J. Farrer. VPS35 Mutations in Parkinson Disease. The American Journal of Human Genetics - 15 July 2011 (Vol. 89, Issue 1, pp. 162-167). www.cell.com/AJHG/abstract/S0002-9297(11)00242-4
Source Date: Jul 15 2011

BOXING LEGEND DIAGNOSED WITH PARKINSON'S DISEASE

9th December 2011 - News report


The former world boxing champion, the Colombian Antonio Cervantes, has been diagnosed with Parkinson's Disease. After Muhammad Ali he is the most successful boxer ever to have Parkinson's Disease. Antonio Cervantes grew up in Colombia shining shoes and selling contraband cigarettes in order to survive. He became a professional boxer whilst still only 18. He became the World Light Welterweight champion in 1972. He held the world title twice, from 1972 to 1976 and 1977 to 1980. He successfully defended his world title 16 times, and had a total of 21 world championship contests. He retired from boxing in 1983 having had 106 contests. Doctors said that he had serious health problems, including difficulties in communicating and eating. He is 65 years old.

NEW INHALED VERSION OF L-DOPA

2nd December 2011 - News release



The Michael J. Fox Foundation has awarded a grant to Civitas Therapeutics for clinical trials of CVT-301, which is a new inhaled version of L-dopa. It is claimed that CVT-301 has the potential to produce rapid, consistent and durable relief from the motor fluctuations associated with Parkinson’s Disease. Civitas has conducted a range of preclinical studies demonstrating CVT-301’s ability to deliver more rapid and consistent systemic exposure of L-dopa compared to the oral administration of L-dopa. The efficacy of oral L-dopa is significantly compromised by delayed absorption and excessive variability in the circulating drug concentrations. It is anticipated that the inhaled version of L-dopa would be used alongside the use of oral L-dopa. 

CVT-301 uses the ARCUS inhalation technology, which delivers a reliable and consistent drug dose with a compact, breath actuated inhaler. It uses a proprietary dry powder and inhaler combination that is unique in its ability to deliver a large, precise dose independent of inspiratory flow rate from a simple, easy-to-use device suitable for convenient self-administration. The platform has successfully delivered more than one million doses to patients incorporating active agents ranging from small molecules to large proteins.

PRAMIPEXOLE (MIRAPEX) INCREASES THE RISK OF HEART FAILURE

7th December 2011 - New research



Pharmacological Research [2011] Nov 23 [Epub ahead of print] (Mokhles MM, Trifirò G, Dieleman JP, Haag MD, van Soest EM, Verhamme KM, Mazzaglia G, Herings R, de Luise C, Ross D, Brusselle G, Colao A, Haverkamp W, Schade R, van Camp G, Zanettini R, Sturkenboom MC.)  The use of pramipexole by people with Parkinson's Disease has been found to increase the risk of heart failure. Pramipexole is a dopamine agonist that is also known as Mirapex, Mirapexin, or Sifrol. For more information go to Mirapex. Pramipexole increased the risk of heart failure in people with Parkinson's Disease by 61%. In the first three months of therapy, the risk of using pramipexole was far greater, as it trebled the risk of heart failure. The risk also increased with age, as the risk of heart failure in those people with Parkinson's Disease over 80 years old taking pramipexole was also trebled. When other dopamine agonists were assessed the researchers found no risk of an increase in heart failure in people with Parkinson's Disease.

INFLUENZA TREBLES THE RISK OF PARKINSON SYMPTOMS


15th December 2011 - New research



Influenza and other respiratory viruses [2011] 5 (5) : 328-333 (S.Toovey, S.S.Jick, C.R.Meier)

Influenza has been found to treble the risk of Parkinson symptoms. Influenza has been associated with Encephalitis Lethargica, a medical disorder causing the symptoms of Parkinson's Disease following the 1918 influenza pandemic.

Recent influenza (influenza in the past month) was associated with a trebling of the likelihood of Parkinson symptoms. Influenza some time in the past year was associated with only a small increase in the likelihood of Parkinson symptoms. The number of previous attacks progressively increased the likelihood of Parkinson symptoms. However, influenza did not increase the likelihood of actual Parkinson's Disease. The relevance of this research may be that people could be wrongly diagnosed with Parkinson's Disease, when what they have actually had is influenza. Around 25% of people are wrongly diagnosed with Parkinson's Disease and do not actually have it.

WORLD'S BEST EVER SQUASH PLAYER DIAGNOSED WITH PARKINSON'S DISEASE

9th October 2011 - News release


Jansher Khan, who is arguably the world's best ever squash player has been diagnosed with Parkinson's Disease at the age of 42, following a series of tests. During his career, Jansher Khan won the World Open a record eight times, and the British Open six times. Jansher Khan officially announced his retirement from squash in 2001. He had won 99 professional titles and was ranked the World No.1 for over six years. Jansher Khan has been showing signs of a mystery illness since last year. His hands would start shaking suddenly. Sometimes he used to act strangely as he his mind went out of control.

WIRELESS SENSOR FOR MEASURING PARKINSON'S DISEASE TREMOR

13th October 2011 - New product

Kinesia HomeView device has been developed to assess Parkinson's Disease tremor. It has been approved for sale in the U.S.A. and several other countries. It combines wireless sensors and a touch-screen tablet to help patients and physicians assess whether medications or neurostimulation therapy are working properly. The patient takes home a motion sensor worn on the finger, plus a touch-screen tablet that includes videos explaining how to take Unified Parkinson’s Disease Rating Scale tests. The tablet gives reminders to take the test several times a day. It measures tremors and, with a built-in camera, records videos of patients whilst taking the test. Patients can keep a diary of their symptoms on the tablet. Via a Web portal, physicians get a report from the system showing the types of tremors and the time of day of each test. Users can also watch videos of the tremors.

AZILECT FAILS TO SLOW PARKINSON'S DISEASE PROGRESSION

19th October 2011 - News release

In It has been claimed by the FDA (the U.S. drug administrators) that Azilect fails to slow the progression of Parkinson's Disease. Azilect is the brand name of Rasagiline, which is an MAO-B inhibitor. MAO-B inhibitors increase dopamine levels by inhibiting Monoamine Oxidase B, which is an enzyme that metabolizes dopamine. Rasagiline is used either on its own or alongside other methods.

The manufacturer, TEVA, claimed that the 1 mg dose of rasagiline (in the ADAGIO clinical study) and the 2 mg dose of rasagiline (in the TEMPO clinical study) could demonstrate a disease modifying benefit in patients with early untreated idiopathic Parkinson’s disease. However, the FDA's analyses "do not support the claim for a disease modifying benefit associated with either dose of rasagiline based on the primary protocol specified analyses or when sensitivity / secondary analyses are applied to the study data sets." For more information go to the FDA report.

In fifteen previous studies Rasagiline caused a moderate reduction in symptoms. It caused a moderate reduction in "off" time in four of those studies. The treatment effect was still evident six weeks after drug discontinuation. One of those studies found Rasagiline to be more effective than Selegiline, which is another MAO-B inhibitor. However, these studies did not demonstrate any slowing of Parkinson's Disease progression. Rasagiline caused infrequent cardiovascular or psychiatric side effects.

PROSAVIN CLINICAL TRIAL RESULTS FOR PARKINSON'S DISEASE

18th December 2011 - News release



Oxford BioMedica, a gene therapy company, have announced updated clinical data from a Phase I/II clinical trial of ProSavin for the treatment of Parkinson’s Disease. ProSavin uses Oxford BioMedica's own LentiVector gene delivery technology to deliver the genes for three enzymes that they suggest are required for the formation of dopamine, the substance whose deficiency causes Parkinson's Disease. The product is administered locally to the relevant region of the brain in order to increase the brain's own capacity for the formation of dopamine. For more information go to ProSavin.

The degree of efficacy is quite moderate and declines after six months. The average improvement in Parkinson's Disease symptoms for all the dosages was about 27% after 3 months. This improved slightly to about 31% after 6 months. The improvements started to decline after that down to 29% after 1 year, and declined further down to only 23% after 2 years. Three dosages were assessed : 1x, 2x and 5x. The level of efficacy declined when the higher 5x dosage was used. More results are expected in 2012 for the 5x dose. An enhanced administration procedure that facilitates higher dosing was used with some patients, but failed to demonstrate any additional benefit.

The safety profile was described as being favourable with no serious adverse events, but details of the side effects were not provided. Oxford BioMedica have claimed that the method could potentially provide more than a 10-fold increase in dopamine formation. However, the moderate improvement in efficacy is entirely inconsistent with that suggestion. Although they have claimed that three genes and enzymes are required for dopamine formation, only two of them are actually needed. Stimulating gene and enzyme levels artificially as they are doing reduces a person's own formation of those genes and enzymes, which is probably why the results start to deteriorate after six months.