Thu10302014

Your Health

Promises for Parkinson's: Researchers' five-year study offers new hope for patients

Photo Courtesy Of El Camino Hospital Researchers tracking participants in the Parkinson's study will view three-dimensional images of nerves and brain tissue mapped by El Camino's high-resolution MRI technology.

 

Hope is on the horizon for patients diagnosed with Parkinson’s disease, a degenerative disorder of the nervous system that affects one in 500 people. More than 1 million people in the United States and an estimated 6.3 million worldwide are afflicted.

The hope lies in a five-year study at 18 sites across the country and in Europe targeted to identify one or more biomarkers of Parkinson’s progression that could aid researchers in developing new and advanced treatments. And perhaps find a cure.

Sponsored by the Michael J. Fox Foundation, the Parkinson’s Progression Markers Initiative (PPMI) will track 400 newly diagnosed Parkinson’s patients who have not initiated drug treatments and 200 individuals who do not have the disease, studying brain images, blood, urine and spinal fluid samples, and behavioral tests.

As one of the sites chosen to participate in the study, Sunnyvale’s Parkinson’s Institute and Clinical Center will collaborate with El Camino Hospital’s Radiology Department to follow 20 Parkinson’s patients and 10 controls.

It’s an exciting time for Dr. Caroline Tanner, who has studied and treated Parkinson’s at the Sunnyvale center for 20 of the 23 years since the center’s inception.

“We’re just starting our enrollment,” she said. “We have six people – three patients, three controls – we’re hoping to enroll 10, although if we have a lot of interest, we could enroll more people.”

Participants will undergo testing quarterly the first year, and twice yearly thereafter, Tanner said.

Identifying any measurable physical characteristic that changes over time that can be tied to Parkinson’s progression – a biomarker – is critical in developing new therapies. The difficulties with current treatments is that they treat the symptoms – the telltale tremors and shaking – but not necessarily the degenerative process that destroys the nerve cells controlling motor functions.

“Right now, we have treatments for motor function – they’re not perfect. Nothing stops, slows or cures the disease,” Tanner said. “Biomarkers help jump hurdles to develop drug therapies. What we’d like to do is know if this person is getting worse … or if this person is getting better.”

 

Imaging

With more than $20 million invested in state-of-the-art imaging equipment, El Camino’s MRI and molecular imaging machinery will image participants’ brains in tracking Parkinson’s progression, as well as the control group for comparing normal images.

As vice chief of the hospital’s Radiology and Nuclear Medicine Department, Dr. Ramesh Gopi will be site investigator for the study’s imaging. MRI and DATScan high-definition images of the brain’s physiology will give researchers a better understanding of Parkinson’s progression.

“It’s very exciting to be a part of this,” Gopi said. “The studies will offer us several snapshots into the course of the disease.”

Researchers have identified two tentative biomarkers for Parkinson’s in the brain, including nerve cells that are injured and the brain’s anatomy, which are amenable to evaluation by molecular imaging and MRI.technology.

For DATScan testing, an iodine-containing radioisotope is injected intravenously, which then binds to the dopamine transporters and clusters within neurons in an area of the brain that governs motor functions – the corpus striatum. In Parkinson’s patients, the neurons’ ability to take up the tracer diminishes over the disease’s progression. As the nerve-cell damage increases over time, so too does the corresponding brightness reflected in the DATScan’s imaging.

“Nobody really knows why (the cells) are damaged – and there was no way to tell how fast the disease is progressing,” Gopi said. “(The images) are very fascinating – it’s an objective way of quantifying what is physiologically happening.”

The MRIs will give doctors a better picture of the brain’s anatomy and normal images for comparison with Parkinson’s, as the disease progresses from its early stages to advanced, as the tremors, motor-function, and in some cases, the cognitive abilities deteriorate.

 

Body biology

In addition to assessing motor functions and neuropsychiatric and cognitive behaviors, the Parkinson’s Institute will test participants’ DNA and olfactory senses – Parkinson’s patients often lose their ability to recognize smells, Tanner said – as well as blood, urine and spinal-fluid samples.

At this stage, doctors and researchers have also identified a protein – alpha-synuclein – as a biomarker in Parkinson’s. The protein clumps in the nerve cells in the corpus striatum of patients with the disease. While the clumps are abnormal, doctors disagree as to whether alpha-synuclein is a cause of the disease or the clumping is a form of protection from the disease, Tanner said.

Key to the study is tracking the body’s biochemicals at the outset of a Parkinson’s diagnosis.

“We want to have enough information about that very early time,” Tanner said. “There is so much we need to learn from this.”

Results may also help determine who is at risk for cognitive faculty losses.

As a medical student studying under a neurologist who was one of the first to pioneer studies in Parkinson’s, Tanner has since focused her training on the disease and its treatments – she helped develop the concept and course of the PPMI study in collaboration with other doctors and the Michael J. Fox Foundation.

“(The foundation) has always tried to fulfill a mission – what gaps need to be filled,” Tanner said.

Part of the mission – establishing the best way to talk with people about the testing involved, particularly the spinal taps for cerebrospinal fluid – is relatively painless. Compared with procedures from years ago, doctors use a much smaller needle.

“It’s simple, painless – the equivalent of a blood draw,” Tanner said. “It isn’t as bad as it’s put out to be.”

 

Sharing knowledge and hope

One of the most important aspects of the trial, Tanner said, is that information will be securely stored at four sites – participants’ personal information deleted – for access by doctors and qualified researchers to study PPMI’s ongoing results. Whether researching information for papers or analyzing data for developing drug therapies, images, body-fluid-test results, behavioral observations and, in some cases, the actual biological specimens themselves will be available for analysis and input by doctors and researchers worldwide.

As Parkinson’s progresses, patients can lose control of the bladder – intestinal complications can affect digestion, balance is lost, swallowing becomes difficult – food can be aspired into the lungs and cause pneumonia, or patients can fall and injure themselves.

“By itself, (Parkinson’s) is not a primary cause of death, usually,” Tanner said. “It’s the complications.”

The institute is seeking control participants who are 30 years or older and are not first-degree blood relatives of Parkinson’s disease patients.

Patients who are newly diagnosed with Parkinson’s or diagnosed with possible PD are needed for the study, too. And though patients should not have begun drug therapies, Tanner said patients might need to begin taking medication during the course of the study.

A diagnosis of Parkinson’s is difficult to accept.

“There are two approaches,” Gopi said. “One, let’s not do anything about it, or two, optimistic outreach. This really offers a lot of hope for patients – and for families.”

Tanner said time has brought many insights and developments in treating Parkinson’s – her hope for the cure.

“We’re definitely continuing to make progress,” she said. “There’s always been progression – we have better treatments. We’re getting close.”

Researchers interested in tracking the study’s progress in real time can visit PPMI’s scientific Web site, www.ppmi-info.org.

For more information or to participate in the Parkinson’s study, call (408) 734-2800 or visit www.thepi.org.

Contact Mary Beth Hislop at This email address is being protected from spambots. You need JavaScript enabled to view it. .

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