Research - August 2014 Archives

Potential biomarker discovered to monitor disease progression, therapy JACKSONVILLE, Fla. — A team of researchers at Mayo Clinic and The Scripps Research Institute in Florida have developed a new therapeutic strategy to combat the most common genetic risk factor for the neurodegenerative disorders amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) and frontotemporal dementia (FTD). In the Aug. 14 issue of Neuron, they also report discovery of a potential biomarker to track disease progression and the efficacy of therapies. The scientists developed a small-molecule drug compound to prevent abnormal cellular processes caused by a mutation in the C9ORF72 gene. The findings come on the heels of previous discoveries by Mayo investigators that the C9ORF72 mutation produces an unusual repetitive genetic sequence that causes the buildup of abnormal RNA in brain cells and spinal cord. While toxic protein clumps have long been implicated in neurodegeneration, this new strategy takes aim at abnormal RNA, which forms before toxic proteins in C9ORF72-related disorders (c9FTD/ALS). “Our study shows that toxic RNA produced in people with the c9FTD/ALS mutation is indeed a viable drug target,” says the study’s co-senior investigator, Leonard Petrucelli, Ph.D., a molecular neuroscientist at Mayo Clinic in Florida. The compound, which was tested in cell culture models of c9FTD/ALS, bound to and blocked RNA’s ability to interact with other key proteins, thereby preventing the formation of toxic RNA clumps and “c9RAN proteins” that results from a process called repeat-associated non-ATG (RAN) translation. The researchers also discovered that c9RAN proteins produced by the abnormal RNA can be measured in the spinal fluid of ALS patients. They are now evaluating whether these proteins are also present in spinal fluid of patients diagnosed with FTD. Although ALS primarily affects motor neurons leading to impaired mobility, speech, swallowing, and respiratory function and FTD affects brain regions that support higher cognitive function, some patients have symptoms of both disorders. “Development of a readily accessible biomarker for the c9FTD/ALS mutation may aid not only diagnosis of these disorders and allow for tracking disease course in patients, but it could provide a more direct way to evaluate the response to experimental treatments,” says co-author Kevin Boylan, M.D., medical director of the Mayo Jacksonville ALS Center, the only ALS Certified Center of Excellence in Florida.

ROCHESTER, Minn. — Mayo Clinic has named a veteran cell biology researcher to head its new Center for Biomedical Discovery. Mark McNiven, Ph.D., brings over 30 years of scientific experience to the position and a decade as leader of Mayo’s Department of Biochemistry and Molecular Biology. The appointment was announced this week by Gregory Gores, M.D., executive dean for Research. “We’re very glad to have someone of Dr. McNiven’s leadership and experience as the director launching this important new center,” says Dr. Gores. “Discovery science is a significant part of our research effort at Mayo Clinic, as it is the starting point in seeking help for our patients when current knowledge isn’t enough.” The Center for Biomedical Discovery was established to grow Mayo’s expertise and build on its foundation of basic research discoveries, which extends back over 100 years. Discoveries in the laboratory form the basis for tomorrow’s clinical care, and Mayo’s scientists have long been teaming with physicians to explore the needs of patients. This Mayo-wide strategic research center will help advance and coordinate those efforts, prioritizing and seeking support to grow the science. The new director will: Promote discovery science as a priority of the institution and a foundation for clinical care Develop programs of excellence with a focus on the molecular basis of disease Promote “team science” and encourage collaboration between scientists and physicians Help implement fundraising strategies for the center Promote innovation and commercialization

PHOENIX — Researchers from Mayo Clinic in Arizona and Banner Sun Health Research Institute have determined that many people with an early diagnosis of Parkinson’s disease are not correctly diagnosed according to a study just published in the journal Neurology. Parkinson's disease is a progressive disorder of the nervous system that affects movement. It develops gradually, sometimes starting with a barely noticeable tremor in just one hand. But while tremor may be the best-known sign of Parkinson's, the disorder also commonly causes stiffness and slowing of movement. Additionally there are many non-movement problems including constipation, loss of the sense of smell, sleep problems, lightheadedness, urinary difficulties, depression and anxiety. Although Parkinson's disease can't be cured, medications may markedly improve symptoms. Currently, there is no accurate diagnostic test for the disease; diagnosis is made based on medical history, a review of signs and symptoms, a neurological and physical examination and by ruling out other conditions. Confirmation of the disease can only be made by performing an autopsy.

ROCHESTER, Minn. — A recent study conducted by Mayo Clinic researchers recommends laparoscopic cholecystectomies (surgical removal of the gallbladder) for pediatric patients suffering from gallstones and other gallbladder diseases. This study was published in Surgical Laparoscopy Endoscopy & Percutaneous Techniques. Journalists: Sound bites with Dr. Ishitani are available in the downloads. A cholecystectomy is a surgical procedure performed to remove the gallbladder, a pear-shaped organ located below the liver on the upper right side of the abdomen. The gallbladder is responsible for collecting and storing bile, which is a fluid secreted by the liver. During a laparoscopic cholecystectomy, four incisions are made in the abdomen. Then, a small video camera and other special tools are used to remove the gallbladder. “Cholelithiasis and other gallbladder diseases requiring cholecystectomies are less common in children compared to adults,” says Michael B. Ishitani, M.D., lead author of the study. “Recently, however, rising rates of obesity in the pediatric population have led to an increase of gallstones found in children. Therefore, it was important for us to review the current clinical practices to ensure that pediatric patients are being treated properly.” Journalists: Sound bites with Dr. Ishitani are available in the downloads.

ROCHESTER, Minn. — If a research survey of African American professional women is any indication, attitudes may be changing towards participation in medical research. Mayo Clinic and The Links, Incorporated researchers teamed up to survey members of the international women’s organization, and found that a majority of African American women surveyed are willing to or have taken part in medical research. The results appear in the Journal of Women’s Health. “Our findings are highly encouraging,” says Sharonne Hayes, M.D., Mayo Clinic cardiologist, co-author of the study, and director of Mayo’s Office of Diversity and Inclusion. “The more African Americans, both women and men, who participate in medical research, the better informed their physicians will be in treating a wide range of conditions. Instead of extrapolating findings from other populations, we’ll have more confidence in diagnostic and treatment recommendations. The authors point to the long-standing distrust of scientists and research studies by many in the African American community, a reaction to unethical experiments in the last century. They say that, for decades, many African Americans did not take part in clinical studies, limiting the data on how diseases among Blacks could be better diagnosed and treated. The study team examined 381 self-administered surveys taken during a 2012 conference of The Links, Incorporated, an organization comprised of college-educated women, the majority involved in a profession. The median age was 59. Just more than half said they felt medical research in America was ethical.