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High Uric Acid Levels Correlate with Slower PD Progression

Men living with Parkinson’s disease (PD) who have naturally high blood levels of urate (uric acid), the agent that causes gout, may experience a slower progression of Parkinson’s and its symptoms, according to a report in the April 14 online edition of Archives of Neurology.

Because urate is an antioxidant, similar in effects to ascorbic acid (Vitamin C), researchers speculate that it can prevent cell damage that results from oxidative stress, which is thought to contribute to PD.

Michael A. Schwarzschild, M.D., Ph.D., and researchers from Massachusetts General Hospital Institute for Neurodegenerative Disease (MGH-MIND) and Harvard School of Public Health (HSPH) performed a prospective study using data from a clinical trial (known as PRECEPT), which enrolled 804 participants between 2002 and 2004. All participants were newly diagnosed with PD at the start of the trial, and took no Parkinson’s medication when their urate levels were first measured.

Dr. Schwarzchild and his colleagues compared participants’ baseline urate levels to the rate of their disease progression. Disease progression was determined by clinical evaluations as well as by a single photon emission computed tomography (or SPECT) scan that measured brain dopamine. The team found that men with the highest baseline levels of urate showed a slower progression of symptoms and required PD medication at approximately half the rate of those with lower baseline urate. According to the SPECT scans, the same group of men showed a slower decline of dopamine cells in the brain. Among women, who generally have lower urate levels than men, the study produced no significant findings.

For some time, scientists have been aware that high levels of urate are associated with a decreased risk of developing PD. The new study shows a correlation between urate levels and slower disease progression in men with early, mild PD.

Although no medication or vitamin has yet been shown to slow the rate of PD progression, the new study offers a new potential treatment approach: drugs that may have effects on urate and its precursors, such as inosine. The authors stress, however, that any benefits must be weighed against urate’s potentially negative effects, such as high blood pressure, stroke, coronary disease, kidney stones, gout and arthritis. They advise people with PD to avoid taking urate supplements until more is known about the balance of its risks and benefits.

Cell Transplants Survive Long Term and May Ease PD Symptoms

Cell transplants used in the experimental treatment of Parkinson’s disease (PD) may survive for many years and may improve some symptoms of the disease. According to three separate studies published in the April 6 issue of Nature Medicine, some brain cell implants may be vulnerable to the effects of PD, while others are not.

The first study, led by Olle Lindvall, M.D., Ph.D., and Patrik Brundin, M.D., Ph.D., of Wallenberg Neuroscience Center in Sweden, studied the brains of two people with PD who had received implants 12 and 16 years prior. Another study, led by Jeffrey H. Kordower, Ph.D., of Rush University Medical Center in Chicago, IL, examined the effects of grafted neurons in a person who had received the treatment 14 years earlier. In all three cases, the person with the implant had died and donated his or her brain to science.

In both studies, researchers found that the implanted cells had survived for up to 16 years. However, the transplants in both studies contained abnormal Lewy bodies — clumps of the protein alpha-synuclein that are a well-known sign of Parkinson’s — implying that the disease had spread to the transplanted cells. This may have implications for future cell transplantation treatments, perhaps limiting the duration of time for which transplants remain effective.

Despite abnormal changes in the implanted cells, researchers noted that the majority of the cells were still functioning years later and some individuals had reported experiencing continuing relief from their Parkinson’s symptoms.

A third investigation, by Ivar Mendez, M.D., Ph.D., F.R.C.S., of Dalhousie University in Halifax, Nova Scotia, and Ole Isacson, M.D., of Harvard Medical School in Boston, MA, examined the brains of five people with PD, who had received transplants between three and 14 years earlier. In contrast to the two other studies, this one found healthy-appearing, surviving transplant tissue, with no signs of Parkinson’s.

To date, the number of people who have undergone brain cell implantation for Parkinson’s is very small, and so no definitive conclusions can be drawn. Researchers remain hopeful about the potential of cell transplantation and will continue to study this technique as a means of treating PD.

Parkinson’s Patch Recalled in US

On March 20, UCB Inc., announced a recall of all US and some European batches of Neupro® (rotigotine transdermal system), a treatment used to ease the symptoms of Parkinson’s disease in its early stages.

Neupro is a dopamine agonist, a dopamine-like drug that shows the same effectiveness as other available agonists, such as pramipexole and ropinirole. The novel aspect of Neupro is its once-a-day application in the form of a skin patch.

Neupro was first approved for use in the United States by the Food and Drug Administration (FDA) in May 2007 for people in early stages of PD. It is not known when and if the medication will be available again in the US, although it is still available in Europe, where the European Medicines Agency (EMEA) has approved its use for those already on the medication (no new patients will be initiated on Neupro).

UCB has stated that the recall was due neither to safety concerns, like contamination or toxicity of the medication, nor to problems with the efficacy of the medication in its true form. Rather, regular monitoring of the patch revealed a problem in its manufacturing that deviated from the approved process. In some cases, this caused the medication to crystallize. Crystallization reduced the amount of the medication that was available to be absorbed through the skin, lowering its efficacy.

People who are using Neupro have been advised to contact their physicians to arrange for their doses to be reduced slowly over time. Sudden discontinuation of the treatment is not advised. Christopher Goetz, M.D., Director of the Parkinson’s Disease Foundation Research Center at Rush University Medical Center in Chicago, IL, noted that physicians will likely recommend switching to another dopamine agonist in place of Neupro.

Impaired Sense of Smell Signals PD Risk in Men

An impaired sense of smell may be an early warning sign of developing Parkinson’s disease (PD) among men, according to a study published in the February 2008 issue of the Annals of Neurology.

From 1991 to 1996, G. Webster Ross, M.D., and his team from the VA Pacific Islands Health Care System and the Pacific Health Research Institute in Honolulu, HI, followed 2,267 men (ages 71 to 95) through the Honolulu Asia Aging Study (HAAS). All men were free of clinical Parkinson’s and dementia at the start of the study. Researchers examined and rated participants’ sense of smell on 12 odor test items, each with four choices.

Dr. Ross’s team found that 35 of these men went on to develop Parkinson’s disease in the next eight years. The incidence of PD was highest among the group that demonstrated the poorest ability to identify odors on the initial tests. Specifically, researchers found that those men with the lowest scores were most likely to develop Parkinson’s within four years of the tests.

These results build upon existing evidence that a poor sense of smell is common in people with Parkinson’s and may be an early indicator of the disease, perhaps present even before motor symptoms emerge. However, most studies linking PD with an impaired sense of smell involve people who already have the disease. This study, a large investigation of people living in the general community, involved people with PD and their family members. It is the first study to demonstrate the development of PD in normal individuals who have an impaired sense of smell.

The authors noted that smell tests, “together with screening for other potential early indicators of PD such as constipation or sleep disturbances, could provide a simple and relatively economical means of identifying individuals at high risk for developing PD who could participate in trials of medications designed to prevent or slow disease progression.”

It is important to note that the research involved only men whose average age was nearly 80 at the start of the study. It is not known whether the study’s conclusions would hold true for women, or for younger individuals. Additionally, there are many other causes for a decreased sense of smell, including coffee intake, cigarette smoking, and the aging process itself.


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