May 30, 2007 by mike.

the scientists could show that Parkin prevents the induction of neuronal cell death. As reported in the “Journal of Neuroscience”, the protein activates a survival mechanism which had been known for its prominent role in immune response.

Little is known about the causes of Parkinson’s disease. It has only been known for a few years that ten to fifteen per cent of all cases are associated with mutations in certain genes.

“The parkin gene is of special interest here”, says Winklhofer. “One effect of its inactivation is that the Parkin protein loses its physiological function. This genetic defect plays a role for hereditary Parkinson’s disease, which may lead to an early onset of the disease.”

However, inactivation of the Parkin protein could also contribute to sporadic forms of the disease. In these cases massive oxidative stress probably results in misfolding and aggregation of the protein. “Interestingly, misfolding of Parkin proteins has recently been observed in the brain of patients with sporadic Parkinson’s disease”, Winklhofer reports.

The scientists could now show in their study that Parkin protects the neuronal cells by mediating the activation of the nuclear protein NF-êB (”Nuclear Factor-kappaB”). This protein is known for triggering a survival programme in many human cells, which prevents cell death under stress conditions. The experiments indicate that mutations in the parkin gene result in an impaired activation of NF-êB.

“This, however, promotes an enhanced susceptibility of neurons to stress-induced cell death”, says Winklhofer. “Further studies will now have to show whether these findings about the function of Parkin in the activation of cellular survival programmes can contribute to the development of new strategies for the treatment of Parkinson’s patients.” Source : GSF - National Research Center for Environment and Health

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May 21, 2007 by mike.

The Parkinson Pipeline Project is a grassroots group of advocates whose goal is to provide the patient perspective in the treatment development process. Through education, consultation, and participation with all stakeholders, including industry and the FDA, the Parkinson Pipeline Project hopes to increase clinical trial participation and accelerate approved treatment options. New PD treatments are followed from pre-clinical development to approval in the Pd Pipeline Database found on our website

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May 21, 2007 by mike.

EH News Bureau

Manipal Hospital, Bangalore claimed of having discovered stem cells that help in recovery of a patient suffering from Parkinson’s Disease (PD). Manipal used the benefits of stem cell research and helped US national Andrew Kisana get a new hope.

Andrew, who was suffering from PD for more than 15 years, came to Manipal Hospital as a last resort after having undergone treatment in US hospitals. After stem cell therapy last year, Andrew has shown remarkable recovery in his symptom as he has started walking without support, there has been significant reduction in the tremors and above all, he has a feeling of well being and personal comfort. His medication for PD has been withdrawn since the last months. This successful recovery of Andrew, will give new hope to many others suffering from debilitating Parkinson’s disease.

Said R Basil, MD and CEO, Manipal Health System, “The successful clinical outcomes from our stem cell research programme have given us the confidence to share this new hope with the public at large so that a greater number of people can participate in the clinical research for getting relief from major diseases and disabilities.”

Led by the Chief Scientific Officer of Stempeutics Research Pvt Ltd, Dr Satish Totey, a team of accomplished stem cell research clinicians will be exploring the full ability of stem cells to address certain diseases and disabilities with limited possibilities of recovery as of today and offer a new hope. The Stem Cell Research Center’s goal is to develop stem cell based therapeutics, using human adult stem cells.

Dr NK Venkataramana, HOD, Neurosurgery, who has been treating Andrew Kisana, presented his case and about the remarkable recovery. While delivering his presentation, Dr Venkataramana said, “Stem cell research seems to be promising in regenerating hope to cure PD. This will motivate innumerable patients across the world to explore this new modality. However, we need to observe the long-term clinical effects in large number of patients to decide its role in the treatment of the degenerative diseases.”

According to Dr Nagendra Swamy, Group Director- Medical Services, Manipal Health Systems, “Stem cell research has attracted wide attention from all medical fields in the world. The research involving human pluripotent stem cells promises new treatment and possible hope for many devastating diseases. This research Centre will promote cutting edge research which can be translated into clinical applications. This would support the in treating the diseases affecting heart, brain, liver, kidney, bone, spinal cord and vascular. This promises to be the future of medicine in coming years and Manipal is proud to be a leader in this science.”

PD typically affects people over the age of 50. The primary treatment of the disease at best removes some of the symptoms but does not stop the progression of the disease.

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May 19, 2007 by mike.

Science Daily — Small doses of the antioxidant coenzyme Q10 appear to increase blood levels of this naturally occurring compound in patients with Parkinson’s disease, but does not improve Parkinson’s disease symptoms, according to an article that will appear in the July 2007 print issue of Archives of Neurology, one of the JAMA/Archives journals.

Parkinson’s disease is a neurodegenerative disorder characterized by tremors and difficulty with walking or other movements. The biological mechanisms underlying the condition are not fully understood, but researchers suspect a malfunction of the mitochondria, parts of the cells that help convert food to energy, according to background information in the article.

Coenzyme (CoQ10), an antioxidant sold as a dietary supplement, is also involved in mitochondrial processes. “Because of these functions, CoQ10 has attracted attention concerning neuroprotective actions in neurodegenerative disorders linked to mitochondrial defects or oxidative [oxygen-related] stress, such as Huntington’s disease and Parkinson’s disease,” the authors write. Previous studies indicate that high doses of CoQ10 (1,200 milligrams) may slow the deterioration associated with Parkinson’s disease.

Alexander Storch, M.D., of the Technical University of Dresden, Germany, and colleagues conducted a randomized clinical trial of a 300-milligram dose of CoQ10 in 131 patients with Parkinson’s disease who did not have changes in motor functions and were on stable treatment for their condition. Those assigned to the treatment group took 100 milligrams of CoQ10 three times daily for three months, followed by a two-month “washout” period. The researchers assessed Parkinson’s disease symptoms before treatment began, each month during treatment and again after the washout period. Blood tests were performed at the beginning of the study, after three months of treatment and after the washout period.

A total of 106 patients completed the full three months of the study–55 in the CoQ10 group and 51 in the placebo group. The compound was well tolerated overall, and the percentage of patients who experienced adverse effects–including viral infection, diarrhea and hearing loss–did not differ between the two groups. Blood levels of CoQ10 increased in the treatment group from an average of 0.99 milligrams per liter to an average of 4.46 milligrams per liter after three months.

“Although we demonstrated a significant increase in plasma levels of CoQ10 toward levels observed with high doses of standard CoQ10 formulations in Parkinson’s disease and other disorders, our study failed to show improvement of Parkinson’s disease symptoms and did not meet its primary or secondary end points,” which were changes on scales that measured Parkinson’s disease symptoms and their effects on physical and mental functioning, the authors write. “Our study further demonstrated that 300 milligrams per day of nanoparticular CoQ10 is safe and well tolerated in patients with Parkinson’s disease already taking various antiparkinsonian medications.”

“Since we did not find symptomatic effects of CoQ10 in Parkinson’s disease, our study does not support the hypothesis that restoring the impaired energy metabolism of the diseased dopaminergic neurons leads to symptomatic benefits in Parkinson’s disease,” the authors conclude. “Future studies will need to explore the protective effects of CoQ10 at the highest effective dose (equivalent to about 2,400 milligrams per day of a standard formulation) over a long treatment period and in a large cohort of patients both sufficient to clearly define the protective potential of this compound in Parkinson’s disease.”

Arch Neurol. 2007;64:(doi:10.1001/archneur.64.7.nct60005).

This study was supported by a grant from the Deutsche Parkinson-Vereinigung eV (German Parkinson Association), Neuss, Germany, and MSE Pharmazeutika GmbH, Bad Homburg, Germany. The co-enzyme Q10 and matching placebo were formulated and packaged without charge by MSE Pharmazeutika.

Note: This story has been adapted from a news release issued by JAMA and Archives Journals.

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May 9, 2007 by mike.

Ijeoma Eleazu, PharmD

Today the FDA approved the first ever skin patch for treating the symptoms of early Parkinson’s disease. Neupro (Rotigotine) belongs to a class of drugs known as dopamine agonists. The patch, manufactured by Schwarz Pharma, delivers a continuous dose of the medication through the skin over a 24-hour period and will need to be replaced every day.

Common side effects of the patch include reactions of the skin at the application site, nausea, vomiting, dizziness, drowsiness, and insomnia. All these side effects are not uncommon for this particular class of drugs. Outside of these more common side effects some potential safety concerns include the possibility of hallucinations, sleep attacks (suddenly falling asleep while performing routine activites such as driving or operating machinery), and a drop in blood pressure upon standing up.

Neupro will be available in doses of 2, 4, 6, and 8mg per 24-hour patches in a silicone base.
 

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May 1, 2007 by mike.

A Conversation With Susan L. Lindquist

On the Trail of Parkinson’s, Through Yeast Cells

Among other accolades, she is a Howard Hughes Medical Investigator, a member of the National Academies of Science and the American Academy of Arts and Sciences, and the 2006 recipient of the Sigma Xi William Procter Prize for Scientific Achievement.

It has all come her way because of her imaginative research into how proteins function. Dr. Lindquist, the former director of the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology, studies how molecular proteins change shape in cell division. The process, called protein folding, can— when it goes wrong — lead to diseases like Alzheimer’s and Parkinson’s.

Last June, Dr. Lindquist and a group of colleagues published a paper in the journal Science reporting new clues about how Parkinson’s develops and how it might be treated.

“Afterward, we received many calls here from people with Parkinson’s,” she recalled in her office at M.I.T.

“It was heartbreaking,” said Dr. Lindquist, 57, who is a founder of FoldRx Pharmaceuticals, a startup biotechnology company seeking to develop drugs to fight Parkinson’s. “We are still many, many years away from a drug. I hated telling people that.”

Q. Your research specialty is a cellular function called protein folding. What exactly is that?

A. The DNA that is within every cell has the task of coding the proteins that carry out a cell’s activities. DNA is made up of the long molecular strings, sort of like a cassette tape containing the code for a symphony. When that tape, the DNA, is plugged into the cell, it instructs the proteins in how to carry out their different functions.

But these proteins, which begin as long strings, have to fold into very specific shapes to do their job. Cells are crowded places, and millions of proteins have to fold into them perfectly. If a protein doesn’t fold up just right, terrible things can happen.

Cystic fibrosis — that’s a loss of function disease caused by a protein not folding correctly. Parkinson’s, Alzheimer’s, Huntington’s disease and some types of cancers are diseases of protein misfolding. With them, the misfolded proteins accumulate inside the cell, interact with things they shouldn’t and send off the wrong chemical signals. That’s what I’ve been studying lately.

Q. Have you found a key to Parkinson’s disease?

A. I think we found a pathway, rather than a key.

We had this idea. We took the gene from a human brain cell that was malfunctioning and was thought to be a cause of Parkinson’s. We inserted it into a yeast cell. The yeast died. Next, we did a very broad genetic analysis and asked, “Which genes can save that cell from the Parkinson’s protein?” We took 5,000 different genes and we tested them one by one. From that, we found several genes, and one that is particularly strong, that express a protein that can save yeast cells from the Parkinson’s gene.

To take the experiment further, we collaborated with some other labs. Together, we took this gene and put it into the brains of nematodes that were engineered to express a human Parkinson’s gene. Sure enough, it saved their neurons from dying. We tried the same thing with fruit flies and then with rat embryonic neurons. The anti-Parkinson’s gene saved them, too. Later, we screened through some 150,000 chemical compounds to see if we could find a substance that saved yeast from Parkinson’s. And we did.

Q. Why start your experiment with yeast, of all things?

A. (Laughs) I know. Even people in my laboratory thought we were crazy to try to study neurodegenerative diseases with a yeast cell. It’s not a neuron. But I thought we might be looking at a very general problem in the way proteins were being managed in a cell. And yeasts are easy to study because they are such simple cells.

As biology has moved forward, we’ve come to realize that the same rules apply to all living things. If there’s a defect in basic cell biology, it might be shared by other cells. So we can learn a lot about complicated organisms from studying very simple cells like yeast.

Q. Did always you want to be a biologist?

A. When I was young, I thought I’d become a nurse or a social worker. Those were the jobs open to women. In college in the late 1960s, there was a lot of hard-core prejudice against women doing science. That’s still somewhat true, though the prejudicial attitudes are more submerged now. Today, about 50 percent of the graduate biology students at the prestigious institutions are female. Yet, only 10 to 15 percent of the professors are.

When I was young, it didn’t seem like the world was open to me. When I got to graduate school, Harvard, there were 1 or 2 women professors among the 65 in the biological sciences department. You could not look at that and think you had a chance.

Sometimes, the bias freed me to take risks. Once early in my career, I wanted to change my research focus from fruit flies to yeast. As you can see, I’ve long been interested in exploiting the special properties of yeast. Someone very senior advised me: “Don’t change your specialty. You’ll never get tenure.” Well, I didn’t think I was going to get tenure anyway. So I made the switch. It led to a big leap in my research.

Q. Lawrence Summers, in his notorious speech, suggested that female scientists might be hindered in their careers because of motherhood. As the mother of two, would you agree?

A. Oh, having children is a lot of work. But one’s circuits are also recharged by them. I do believe that coming home to them, watching them grow, has helped my science. Kids change your thought patterns around. That’s good for your brain.

Q. You give lectures to younger women scientists about career building. What do you advise?

A. I talk about the personal aspects. I tell them if they want to have a family, they’d better pick a partner who’s going to support their work.

Another thing, they have to make mindful financial choices.

For example, when I had my two children, I was at the University of Chicago. I saw how a lot of my female colleagues, as soon as they got tenure, bought houses in the suburbs, which ate up their money and spare time. My husband and I stayed in our Hyde Park apartment, which was near the lab. We used my salary to hire a really good nanny. I always put my resources into things that kept me from falling apart and helped my kids.

Q. How did you find a supportive life partner?

A. I put a lot of careful thought into this. I had an earlier marriage which didn’t work out. When I started dating again, I knew I wanted children. So I consciously looked for a man who’d be a great partner for that.

I tried blind dates, I went to parties I had no interest in. Eventually, I met my husband at a party that some students gave for their favorite professors. He taught medieval French literature. I had wanted a nonscientist. I have a lot of nonscientific interests and I wanted my partner to be someone who brought different intellectual content to my life.

Q. Is this an exciting time to be a biologist?

A. Unbelievable. I have to tell you that the sheer intellectual joy of finding out how life works is really cool. This is the greatest intellectual revolution, and it is happening right now, and I’m lucky enough to be in the middle of it.

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