Breaking News
September 24, 2018 - King’s commemorates opening of new NMR facility with one-day symposium
September 24, 2018 - Eisai receives approval for partial label change of DC Bead device for transcatheter arterial embolization
September 24, 2018 - High-resolution genomic map gives scientists unprecedented view of brain development
September 24, 2018 - Alexion announces positive results from Phase 3 PREVENT study of Soliris in patients with NMOSD
September 24, 2018 - First evaluation of benefits, harms of Alzheimer’s screening for family members of older adults
September 24, 2018 - Children of mothers using cannabis may start using it at an earlier age, finds study
September 24, 2018 - Most patients who underwent transcatheter valve replacement experience prosthesis-patient mismatch
September 24, 2018 - New study provides basis for Air Canada to change its facial hair policy for aircrew
September 24, 2018 - Infant walkers lead to thousands of emergency visits for babies
September 24, 2018 - Genes predicting person’s height may provide clues about causes of varicose veins
September 24, 2018 - EPA Plan Will Maintain Carbon Emissions From Power Plants
September 24, 2018 - Characterizing pig hippocampus could improve translational neuroscience
September 24, 2018 - Element3 Health reports social and mental engagement play key role in overall health
September 24, 2018 - Paralympic medalists support Fight for Sight’s unique virtual event
September 24, 2018 - ADCETRIS drug receives approval in Japan as frontline treatment option for Hodgkin lymphoma
September 24, 2018 - Public awareness of urological conditions found to be alarmingly low across Europe
September 24, 2018 - Fitter Folks Suffer Milder Strokes: Study
September 24, 2018 - Novel botulinum toxin compound relieves chronic pain
September 24, 2018 - CHMP recommends approval of Gilenya for treatment of multiple sclerosis in children, adolescents
September 24, 2018 - National Friendly’s private medical insurance is a hit with women living in the South East
September 24, 2018 - Academics receive prestigious awards for achievements in blood pressure research
September 24, 2018 - Obese pregnant women can restrict weight gain safely with proper nutrition guidance
September 24, 2018 - CHMP adopts positive opinion of Takeda’s ALUNBRIG for treatment of ALK+ non-small cell lung cancer
September 24, 2018 - China NMPA approves LENVIMA for treatment of unresectable hepatocellular carcinoma
September 24, 2018 - A new approach for finding Alzheimer’s treatments
September 24, 2018 - USC research uncovers previously unknown genetic risk factor for dementia
September 24, 2018 - Study examining mental health among students finds significant disparities in treatment across race
September 24, 2018 - Breakthrough discovery paves way for future test to identify drowsy drivers
September 24, 2018 - Transcatheter mitral-valve repair in patients with heart failure
September 24, 2018 - Study opens new avenues for treatment of Laing distal myopathy
September 24, 2018 - Stroke Facts | cdc.gov
September 24, 2018 - Sarcolipin tricks muscle cells into using more energy, burning fat
September 24, 2018 - Enrollment in opioid controlled substance agreement reduces primary care visits
September 24, 2018 - UTA researchers patent new smart seat cushion technology that helps prevent painful ulcers
September 24, 2018 - Second HPV-Related Primary Cancers Common in Survivors
September 24, 2018 - How a virus destabilizes the genome
September 24, 2018 - Old letters provide insight into Spanish flu pandemic horror
September 23, 2018 - Smart textile-based soft robotic exosuit helps wearers save energy and traverse difficult terrain
September 23, 2018 - New research hub to drive radical change in development and manufacturing of vaccines
September 23, 2018 - AHA: For Hispanics, Neighborhood May Be Key Factor in Heart Disease Risk
September 23, 2018 - Excessive airway nerves tied to more severe asthma symptoms, study finds
September 23, 2018 - Study highlights need to remain vigilant in maintaining key infection control processes
September 23, 2018 - Novel therapeutic strategy for blood vessel related disorders, such as cancer and retinopathy
September 23, 2018 - New naturally occurring antibiotic found effective against Mycobacterium tuberculosis
September 23, 2018 - First-in-human phase 0 study shows clinically-relevant activity of new drug in glioblastoma
September 23, 2018 - Removing tobacco product display from shops reduced number of children buying cigarettes
September 23, 2018 - Random fraction of specialized immune cells leads the charge in battling invaders
September 23, 2018 - Few minutes of sprinting exercise may be as effective as longer exercise sessions
September 23, 2018 - Researchers use neutrons to make first direct observations of water in lipid bilayers
September 23, 2018 - Researchers demonstrate pre-clinical success for universal flu vaccine in new paper
September 23, 2018 - Study reveals surprising gaps in some HIV medical providers’ knowledge of ACA
September 23, 2018 - Oxehealth secures European medical device accreditation for vital signs measurement software
September 23, 2018 - HTN Tx Intensification Common Upon Discharge in U.S. Vets
September 23, 2018 - Fibre can strengthen the intestinal barrier
September 23, 2018 - New platform examines infectious pathogens that may spread from animals to humans
September 23, 2018 - Demographers create detailed color map of population aging in Europe
September 23, 2018 - New type of fatty acid can slow down overreactive immune system
September 23, 2018 - Innovative procedure could provide breakthrough in treating early-stage lung cancer
September 23, 2018 - Research finds drop in number of measles cases in the EU/EEA since March 2018
September 23, 2018 - Researchers acquire new insights into DNA polymerases
September 23, 2018 - Alzheimer’s diagnosis might become simpler with new brain imaging method
September 23, 2018 - Reports Warn of Growing Opioid Crisis Among Seniors
September 23, 2018 - Researchers unravel why people with HIV suffer from more neurologic diseases
September 23, 2018 - Human brain structured to make best possible decision with limited resources
September 23, 2018 - KHN’s ‘What the Health?’ Health on the hill
September 23, 2018 - Bad air and inadequate data prove an unhealthy mix
September 23, 2018 - Regular bedtime and wake time important for heart, metabolic health even among adults
September 23, 2018 - HIV and a tale of a few cities
September 23, 2018 - NIH launches clinical trial to test infusions of combination antibodies in people with HIV
September 23, 2018 - Researchers develop new system to detect consumption of synthetic cannabinoids
September 23, 2018 - Vax-Hub to influenze radical change in development and manufacturing of vaccines
September 23, 2018 - People who have slept lesser than seven hours have higher risks of car crashes
September 23, 2018 - an ancient art may work best to prevent falls in old age
September 23, 2018 - Consumption of foods with lower nutritional quality related to increased cancer risk
September 23, 2018 - Patient Health Information Often Shared Electronically
September 23, 2018 - Can machine learning bring more humanity to health care?
September 23, 2018 - Body organs undergo structural changes in response to diet
September 23, 2018 - Genetic polymorphisms linked with muscle injury and stiffness
September 23, 2018 - As states try to rein in drug spending, feds slap down one bold Medicaid move
September 22, 2018 - Why Eczema Is Tougher to Treat for Black Patients
Genetic model offers elegant tool for testing Parkinson’s disease therapies

Genetic model offers elegant tool for testing Parkinson’s disease therapies

image_pdfDownload PDFimage_print
Immunohistochemistry for alpha-synuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson’s disease. Credit: Wikipedia

For the past decade, Parkinson’s disease researchers have relied on the experimental equivalent of using a sledgehammer to tune a guitar to test new therapies for the disease. This may be a reason clinical trials of promising neuroprotective drugs fail. But, in new research published today in Nature Parkinson’s Disease, University of British Columbia researchers may have found the ideal tool for the job.

“We believe we’ve found an approach that is most relevant to humans, in that our models of gene dysfunction mimic the etiology of Parkinson’s disease rather than its pathology— meaning its beginning rather than its end,” says Matthew Farrer, the study’s lead investigator and a researcher at the Djavad Mowafaghian Centre for Brain Health at UBC. “This means we’re looking at the disease before it becomes symptomatic, before it begins affecting an individual’s motor skills or cognition.”

Parkinson’s disease symptoms are associated with the progressive loss of dopamine-producing nerve cells. Over time, these cells effectively become out of tune, and eventually they stop working altogether.

Until now, the best available experimental models of the disease were based on flooding the brain with alpha-synuclein—a protein in the brain that, when it accumulates abnormally into clumps, is linked to Parkinson’s—or using neurotoxins to destroy dopamine-producing cells. These conventional models exhibit the classic motor and behavioural symptoms of the disease, which is why they have been widely adopted by the Parkinson’s field, but the sledgehammer approach to inducing the disease means the cells die—the guitar is smashed—before any of the subtle changes in the tune can be measured.

According to Parkinson Canada, the disease affects about 100,000 Canadians and 7 million people worldwide. A great many patients are put at elevated risk for disease because of mutations in a gene called LRRK2—a discovery Farrer and colleagues made in 2004.

So far, no LRRK2-specific drugs developed as a neuroprotective treatment for Parkinson’s have achieved FDA approval for the treatment of Parkinson’s disease, and some companies have abandoned their LRRK2 programs due to potential side effects.

The new model, developed by Farrer and his team could offer the precise tool that researchers have long hoped would deliver the impact of LRRK2 inhibitors and other disease-modifying drugs.

The model—known as a VPS35 D620N knock-in (VKI)—induces the biology of a disease-causing gene rather than the symptoms of the disease. Although the model shows no behavioral signs of Parkinson’s, their new study found the changes in biology are clear and elegantly precise. As a tool for preclinical research, it gives scientists something to measure and, ultimately, to fix with promising neuroprotective drugs.

The lab’s recent work to characterize the VKI model shows it is critically important in dopamine neurotransmission, where it regulates the activity-dependent recycling of the dopamine transporter. While the team was the first to suspect a relationship between LRRK2 and VPS35 in 2012, when they initially discovered the role of VPS35 in Parkinson’s, it is novel to observe activity-dependent changes in dopamine release and reuptake due to a single point mutation.

“What’s really exciting for us is that everything we’re seeing is pointing to an early change in synaptic activity,” says Igor Tatarnikov, a graduate student working with Farrer to characterize the VKI model. “It’s something we might rescue with the right drugs, and something we might visualize, because LRRK2 and VPS35 affect the same biological pathway. We’re hoping to use PET imaging to provide a clinically relevant biomarker, which would be relevant beyond genetic forms of the disease. In the future, our hope is that people who carry the VPS35 mutation may be an ideal group for clinical trials.”

“VKI mice provide one of the tools to quantify the minimal dose of LRRK2 kinase inhibitors to see neuroprotective benefits, and so advance therapeutic trials in human patients,” says Farrer. “Imagine if we could begin helping people at risk of Parkinson’s disease as early as their 40s and 50s. We believe we’re in the right key with LRRK2 and VPS35, now it’s just a matter of arranging the notes.”


Explore further:
Parkinson’s treatments being developed could benefit most people with the disease

Provided by:
University of British Columbia

Tagged with:

About author

Related Articles