Advanced MRI scans may help treat essential tremors and Parkinson's disease

Researchers at UT Southwestern Medical Center have recently developed MRI techniques used to more precisely target a small area in the brain linked to Parkinson's disease and essential tremor. This may lead to better outcomes without surgery and with less risk of negative effects of treatment of tremors and Parkinson's disease.

The study have been published in the journal Brain.

The research describes recently refined MRI methods designed to allow neuroradiologists to zero in on a pea-sized region in the brain's thalamus involved in movement. Using the images, doctors then can use high-intensity focused ultrasound (HIFU) to ablate, or burn away, problem tissue, says Bhavya R. Shah, M.D., first author of the study and an assistant professor of radiology and neurological surgery at UT Southwestern's Peter O'Donnell Jr. Brain Institute.

"The benefit for patients is that we will be better able to target the brain structures that we want," Shah says. "And because we're not hitting the wrong target, we'll have fewer adverse effects." The procedures are already Food and Drug Administration-approved for use in patients, and UTSW plans to begin employing them to treat patients when its Neuro High Intensity Focused Ultrasound Program opens this fall.

Adverse effects from imprecise targeting include problems walking or slurring words. While such effects are usually temporary, they can be permanent in 15 to 20 percent of cases, says Dr. Shah.

According to the National Institutes of Health, essential tremor affects up to 10 million Americans and Parkinson's disease impacts more than 1 million. Both are neurologic diseases thought to have genetic links. The first line of treatment for the involuntary trembling or shaking seen with these diseases is medication. However, approximately 30 percent of patients do not respond well to drugs, according to the study.

In the late 1990s, neurosurgeons began using a procedure called deep brain stimulation, opening the skull to permanently implant metal electrodes that could then be stimulated via a battery pack.

About a decade ago, a new MRI-guided procedure emerged that uses high-intensity ultrasound waves to heat and eliminate a small section of the thalamus linked to the disorders. MRI-guided HIFU is currently approved for treatment of essential tremor and tremors seen in Parkinson's disease patients. The outpatient procedure does not require opening the skull, and the patient is awake while it is performed, says Dr. Shah. "No cuts. No anesthesia. No implanted devices."

A challenge in both procedures has been locating the precise area inside the brain's thalamus to treat - the pea-sized ventral intermediate nucleus, says Dr. Shah.

Traditionally, doctors have relied on either landmarks or maps of the brain drawn from cadavers to help them pinpoint the correct location. However, every brain is different, Dr. Shah says, and tiny errors can lead to damage in surrounding tissue, or to missing portions of the correct target.

Three newly refined MRI techniques are better at delineating the target tissue, according to the study.

The most widely studied and perhaps most promising imaging method is called diffusion tractography, says Dr. Shah. It creates precise brain images by taking into account the natural water movement within tissues.

The other methods described are quantitative susceptibility mapping - which creates contrast in the image by detecting distortions in the magnetic field caused by substances such as iron or blood - and fast gray matter acquisition TI inversion recovery - which operates much like a photo negative, turning the brain's white matter dark and its gray matter white in order to provide greater detail in the gray matter.

Dr. Shah and his team plan to participate in a multicenter clinical trial with collaborators at the Mayo Clinic in Rochester, Minnesota, testing the diffusion tractography method in patients.

 

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Foot and mouth disease virus to help treat pancreatic cancer

The dreaded pancreatic cancer has the lowest survival rates among all types of cancers. However, a group of scientists are using the foot and mouth disease virus to find a cure for this often lethal condition.

The research team from the Queen Mary University of London has identified a peptide, or protein fragment, taken from the foot-and-mouth-disease virus that targets another protein, called AvB6 (alpha-v-beta-6). This protein is found at high levels on the surface of the majority of pancreatic cancer cells.

The study was published in Theranostics.

Working jointly with Spirogen and ADC Therapeutics, the team have used the peptide to carry a highly potent drug, called tesirine, to the pancreatic cancer cells. When mice with pancreatic cancer tumours were treated with the drug and peptide combination, the tumours were completely killed.

"Foot-and-mouth-disease virus uses AvB6 as a route to infect cattle, as the virus binds to this protein on a cow's tongue. By testing pieces of the protein in the virus that attaches to AvB6, we've developed a route to deliver a drug specifically to pancreatic cancers," said John Marshall, lead researcher professor from the Cancer Research UK Barts Centre.

The team performed tests of the peptide/tesirine combination in both cells in the laboratory and in mice.

Mice that had AvB6-positive tumours were given a tiny dose of the peptide-drug combination three times a week, and this stopped the tumours growing completely. But when the dose was increased and given just twice a week, all tumours in mice that were AvB6 positive were completely killed.

From the experiment, scientists were excited to offer a completely new way of treating pancreatic cancer.

Prof Marshall explained "One advantage of targeting AvB6 is that it is very specific to cancer because most normal human tissues have little or none of this protein. So we're hopeful that, if we can develop this into an effective treatment for pancreatic cancer, it would have limited side effects."

The team now plan to further test the peptide and drug combination in more complex mice models, to determine if it can also impact on pancreatic cancer metastases, before moving to clinical trials.

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