Gene Therapy May Improve Parkinson's Symptoms

Clickbank Products Gene Therapy May Improve Parkinson's Symptoms



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Study Shows Improvement in Tremors After Injection of Genetic Material Into Brain

By Salynn Boyles
WebMD Health News

Reviewed by Laura J. Martin, MD

March 16, 2011 -- An experimental gene therapy injected into the brains of patients with Parkinson's disease improved tremor, stiffness, and other movement symptoms and was safe with few side effects over six months of follow-up, a study shows.

The small study represents the first successful clinical trial comparing a gene-based treatment to sham treatment in Parkinson's or any neurologic disorder, says Michael Kaplitt, MD, PhD, who developed the gene therapy more than a decade ago. He hopes to market it if phase III trials confirm its effectiveness.

Kaplitt is vice president for research in the department of neurological surgery at Weill Cornell Medical College in New York City. He is a co-founder of the company Neurologix, which is developing the treatment and funded the study.

"For almost two decades we have recognized that gene therapy holds great promise for treating neurological diseases like Parkinson's and Alzheimer's," Kaplitt tells WebMD. "The problem has been translating that promise into reality."

Gene therapy involves the use of genes to treat or prevent disease. The genes are transferred into targeted cells via viruses that have been rendered harmless.

While other gene-based treatments have shown promise for the treatment of Parkinson's disease in studies involving primates, the few that have made it to human trials have failed to show a clear benefit over sham treatments, Kaplitt says.

The 45 patients in the newly reported phase II study had moderate to advanced Parkinson's symptoms that were not adequately controlled with conventional treatments. They were treated at seven medical centers in the U.S.

Half got the gene therapy, which involved the infusion of genetic material directly into a key brain regions associated with motor function through tiny holes drilled in the brain.

The gene used in the treatment, glumatic acid decarboxylase (GAD), makes a chemical called GABA, which helps reduce the excessive firing of neurons that lead to Parkinson's symptoms.

In the sham portion of the study, neurosugeons drilled holes halfway through the patients' skulls and pretended to attempt to locate the exact location to place a catheter. This involved no small amount of acting, since the patients remained awake during the surgery in the belief that they were helping the surgeons locate the key brain regions.

The other patients in the study received the gene therapy delivered via catheter in a two-hour infusion. The researchers mimicked the infusion procedure in the sham-therapy patients.

Sixteen of the patients who got the gene therapy and 21 who got the sham surgery completed the study and were included in the analysis.

Over six months of follow-up, half of the gene therapy patients achieved significant improvement in symptoms, compared to 14% of the comparison patients.

Overall, the gene therapy patients had almost twice the improvement in motor scores as those who received the sham surgery: 23% vs. 12%.

Improvements in motor control were seen at one month and continued virtually unchanged throughout the six-month study, Kaplitt says.

The study was published online today in the journal Lancet Neurology.

Study researcher Andrew Feigin, MD, says the gene therapy is a completely novel approach to treating Parkinson's disease.

Feigin is an associate professor of neurology and molecular medicine at The Feinstein Institute for Medical Research in Manhasset, N.Y. He has no ties to Neurologix and is not involved with developing the gene therapy.

Feigin tells WebMD that it is not yet clear if the treatment is more effective or is as effective as deep brain stimulation (DBS), which is the most widely used surgical treatment for Parkinson's disease.

"Even if this proves to have comparable or even near-comparable efficacy to DBS, I would think that it might still have a place in treatment," he says. "Most importantly, this study shows this kind of therapy can be done safely."

SOURCES: LeWitt, P.A. Lancet Neurology, published online March 17, 2011.Michael Kaplitt, MD, PhD, vice chairman for research, department of neurological surgery, Weill Cornell Medical College; neurosurgeon, New York Presbyterian Hospital; co-founder, Neurologix Inc.Andrew Feigin, MD, associate professor of neurology and molecular medicine, The Feinstein Institute for Medical Research, Manhasset, N.Y.News release, New York-Presbyterian Hospital/Weill Cornell Medical Center.News release, Feinstein Institute for Medical Research.

©2011 WebMD, LLC. All Rights Reserved.

Therapy,Improve,Parkinsons,Symptoms

New Insight on Weight Gain After Prostate Cancer Therapy

Clickbank Products New Insight on Weight Gain After Prostate Cancer Therapy



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Study Shows Weight Gain After Hormone Therapy May Level Off After a Year of Treatment

By Brenda Goodman
WebMD Health News

Reviewed By Laura J. Martin, MD

March 14, 2011 -- Many men with prostate cancer will get treatments to block male hormones like testosterone in an effort to keep their cancer from spreading.

There are several recognized side effects associated with those therapies, including hot flashes, loss of interest in sex, erectile dysfunction, bone loss, mood changes, and weight and body composition shifts. Body composition is a loss of muscle and bone mass with an increase in fat mass.

Now a new study shows that the weight gain -- about 9 pounds, on average -- associated with a form of hormone therapy called androgen deprivation therapy (ADT) appears to level off after the first year of treatment. It's a finding that experts say is useful in helping doctors and patients who are trying to manage that extra girth, which studies have shown may increase the risks of diabetes and heart disease.

"The changes in body composition are a substantial side effect for which we don't have a great solution yet," says Philip J. Saylor, MD, instructor in medicine and a clinical oncologist at Massachusetts General Hospital, in Boston. "It's helpful to know that it doesn't lead to progressive changes throughout the course of a prolonged treatment. It's helpful to know that most of the change happens early and that additional therapy doesn't bring additional changes in body composition." Saylor reviewed the study for WebMD but was not involved in the research.

The study's researchers say the finding underscores the need for doctors to use these treatments, which include either surgical removal of the testes or drug therapy, conservatively.

"I'm using hormonal therapy a lot less than I was a few years ago because I do realize it is a very effective, albeit toxic therapy," says study researcher Stephen J. Freedland, MD, associate professor at the Duke Prostate Center and a staff physician Veterans Affairs Medical Center, in Durham, N.C.

"There's a growing body of data, to which our study contributes, that says there are clearly side effects with these therapies, so let's make sure that there's actually the possibility of benefit before we do this," he says.

The study relied on medical records of 132 men who underwent radical prostatectomies with subsequent androgen deprivation therapy at four Veterans Affairs hospital. The patients were enrolled in the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

The average age of the study participants was 66. Half were white, 42% were African-American, and 8% came from other races.

A majority of men on ADT, 70%, gained weight -- an average of about 9 pounds per person. But 26% of men lost an average of 5 pounds each after starting ADT, and 4% saw no weight change.

In a subset of 84 men who had recorded weights for all three years of the study, researchers saw a distinct bump in weight during the first year on ADT, with no changes in the year before therapy or in the second year.

The study is published in the March issue of the urology journal BJUI.

"When we discuss this in clinic as a potential and likely side effect, I tell patients that it's hard for most men to maintain or lose weight, and androgen deprivation therapy is going to make that harder than it already was," Saylor says.

Beyond weight gain, previous studies have shown that ADT causes changes in body composition -- a loss of muscle and bone mass with an increase in fat mass.

"So not only is the total amount of body weight going up, but it's in the wrong proportions," Freedland says. "It is a big problem."

Those changes are thought to increase insulin resistance, which may, in turn, increase the risks for heart disease and diabetes.

"Our key tools for fighting against that really are diet and exercise," Saylor says.

Freeland agrees, noting that there are studies under way to try to see what the best diets or exercise plans may best help men on hormone therapy peel off unwanted pounds, but the jury is still out on which is most effective.

In the meantime, he says the best guidance is the mantra followed by people who need to lose weight under any circumstances: Move more, eat less.

SOURCES: Kim, H. BJUI, March 2011.News release, BJUI, March 2011.Stephen J. Freedland, MD, associate professor, Duke Prostate Center; staff physician, Veterans Affairs Medical Center, Durham, N.C.Philip J. Saylor, MD, instructor in medicine, clinical oncologist, Massachusetts General Hospital, Boston.

©2011 WebMD, LLC. All Rights Reserved.

Insight,Weight,After,Prostate,Cancer,Therapy

Study Explains How Shock Therapy Might Ease Severe Depression

Clickbank Products Study Explains How Shock Therapy Might Ease Severe Depression



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By Carina Storrs
HealthDay Reporter

MONDAY, March 19 (HealthDay News) -- A small new study gives insight into how electroshock therapy, an effective yet poorly understood treatment for severe depression, affects the brains of depressed people.

Researchers used functional MRI scans to look at brain activity in nine adults with severe depression before and after electroshock therapy. The investigators found that electroshock, or electroconvulsive therapy (ECT), dampens the connections between different areas of the brain in depressed people.

"With our study we were able to confirm that there is hyperconnectivity [in depression], and in addition we could show that treatment removes it," said study co-author Christian Schwarzbauer, a professor of neuroimaging at the University of Aberdeen in Scotland.

Although it may seem counterintuitive that people with severe depression, who are often also lethargic, would have brains on overdrive, one explanation could be that they have too much internal brain activity and cannot deal as well with external stimulation, Schwarzbauer said.

This study could point to ways to improve electroshock therapy's effectiveness and safety, he added. In its 76-year history, the treatment has met with opposition from doctors because of concerns of its side effects, such as memory loss.

Electroshock therapy is typically only used for patients who have not responded to antidepressants or other types of treatment and are at risk of hurting themselves or others.

"I think the fact that now there's more of an explanation, I think that's reassuring to the clinician as well as the patient," said Jennifer Perrin, who is a research fellow at the University of Aberdeen and lead author of the study published online March 19 in the Proceedings of the National Academy of Sciences.

For the study, nine severely depressed participants underwent functional MRI scans of their whole brain before and after a series of electroshock therapy. They received the treatment twice a week until their symptoms, including sadness and fatigue, subsided.

The participants had not responded to antidepressant drugs before the study or received electroshock therapy in the past six months, although four of the patients were taking antipsychotic medications.

The researchers zeroed in on an area in the front of the brain called the dorsolateral prefrontal cortex. It had fewer and less intense connections with a number of other areas of the brain following electroshock therapy, the scans showed.

This particular part of the brain is involved in cognition [thought processes] and social behavior and has been implicated in depression, so this finding is not surprising, said Tony Tang, an adjunct professor of psychology at Northwestern University. What is surprising, he said, is that none of the many other brain areas that have been associated with depression were found to have cut-off lines of communication following electroshock therapy.

"ECT is a rather invasive, drastic procedure and you see a lot of changes in patients, so we would probably speculate that there would be some sort of widespread brain connectivity changes," Tang said. This study "found it to be localized, and I found that to be rather amazing."

During electroshock treatment, clinicians place electrodes on the scalp and, while the patient is under anesthesia, deliver enough electric current to induce a seizure. The therapy is more effective when electrodes are on both sides of the head, as opposed to just one, but unfortunately this also carries greater risk of side effects.

Having electrodes on both sides of the head may be more effective because it triggers a more widespread seizure, but the current findings suggest another possibility, Tang said: When clinicians put electrodes just on one side of the scalp, they usually put them over the right half of the brain because it is less dominant (for right-handed people). However, according to this study, the dorsolateral prefrontal cortex, in the left side of the brain, could be the crucial area to target.

"Most localized forms of stimulation we've tried so far don't work as well [as having electrodes on both sides], but this type of study could potentially point to the right direction," Tang said.

Looking at brain connections in people with severe depression could help clinicians predict who will benefit from electroshock therapy as well as who will relapse after treatment, Schwarzbauer suggested. Between about 60 percent and 80 percent of people become depressed again, usually within six months of the treatment.

Beyond depression, functional MRI of the entire brain could offer insights into other conditions that could be related to changes in brain networks, including autism, schizophrenia and dementia, Schwarzbauer said.

Copyright © 2012 HealthDay. All rights reserved. SOURCES: Christian Schwarzbauer, Ph.D., chair, neuroimaging, University of Aberdeen, Aberdeen, Scotland; Jennifer Perrin, Ph.D., research fellow, University of Aberdeen, Scotland; Tony Tang, Ph.D., adjunct professor, psychology, Weinberg College of Arts & Sciences, Northwestern University, Chicago; March 19, 2012, Proceedings of the National Academy of Sciences, online

Study,Explains,Shock,Therapy,Might,Severe,Depression