Breaking News
February 21, 2018 - ‘Grey’s Anatomy’ Traumas Lack Realism
February 21, 2018 - Sleep quality improves with help of incontinence drug
February 21, 2018 - Scientists uncover genetic cause behind typhoid’s antibiotic resistance
February 21, 2018 - Study reveals a significant link between heavy alcohol use and dementia
February 21, 2018 - French scientists develop new wearable laser that eradicates skin conditions
February 21, 2018 - People with major depressive disorder have reduced arginine levels, study shows
February 21, 2018 - National Health Spending at $3.5 Trillion in 2017, CMS Says
February 21, 2018 - Substantial inequalities in cesarean births persist in many countries
February 21, 2018 - Early childhood immune signature predicts risk of developing asthma later on
February 21, 2018 - Stanford researchers explore how gut bacteria respond to common changes in habitat
February 21, 2018 - Household Products May Pollute the Air as Much as Your Car Does: Study
February 21, 2018 - Combo Bests Targeted Agent in mRCC
February 21, 2018 - Researchers discover brain pathway that dissociates opioid addiction from analgesia
February 21, 2018 - Scientists uncover how newly discovered gene helps grow blood vessels
February 21, 2018 - Brain’s quality control process holds clues to obesity’s roots
February 21, 2018 - Researchers to study whether menstrual cups can help prevent vaginal infections
February 21, 2018 - MS patients who feel stigmatized more likely to suffer from depression
February 21, 2018 - Vitamin D supplementation during pregnancy could protect against childhood obesity
February 21, 2018 - Lower-Quality Medical Tx Might Have Skewed Key PCI vs CABG Trials
February 21, 2018 - Love and fear are visible across the brain instead of being restricted to any brain region
February 21, 2018 - Researchers discover potential new antimalarial treatment targets
February 21, 2018 - Adults with congenital heart disease have increased risk for dementia, study finds
February 21, 2018 - Clinical trial studying type 1 diabetes reaches full enrollment
February 21, 2018 - Father’s stress affects the brain development of offspring, mice study shows
February 21, 2018 - ESRD Death Declines in Vasculitis Patients
February 21, 2018 - Taking ibuprofen for long periods found to alter human testicular physiology
February 21, 2018 - Google AI device could predict a person’s risk of a heart attack
February 20, 2018 - FDA Approves Domestic Source for Tc-99m Isotopes
February 20, 2018 - Sanofi rejects refund demand faces Philippine suit over dengue vaccine (Update)
February 20, 2018 - Researchers discover that activation of specific enzyme may help suppress tumor metastasis
February 20, 2018 - Blood or marrow transplantation survivors have higher risk of cognitive impairment
February 20, 2018 - Booze Beats Pot at Being Unhealthy: Oregon Poll
February 20, 2018 - Morning Break: ’20 Years Late’; Drugs in the Dirt; Catching Flu in the Dorm
February 20, 2018 - Another piece to the puzzle in naked mole rats’ long, cancer-free life
February 20, 2018 - Scientists identify four viruses that can produce insulin-like hormones
February 20, 2018 - New e-Health solution developed to prevent cardiovascular disease, dementia in senior citizens
February 20, 2018 - New genetic risk score could help guide screening decisions for prostate cancer
February 20, 2018 - Study finds higher risk of stroke among blacks with atrial fibrillation than whites
February 20, 2018 - Physical activity could be used as strategy for diabetes prevention
February 20, 2018 - Researchers develop sensing method for early detection of cancer and diabetes
February 20, 2018 - New wearable electronics could be game-changer for stroke rehabilitation
February 20, 2018 - Immune history influences person’s response to flu vaccine
February 20, 2018 - Research findings could help develop new drugs to prevent, treat dry eye disease
February 20, 2018 - Serenity Now! Learn to Have Patience with Patients
February 20, 2018 - Computer simulation addresses the problem of blood clotting
February 20, 2018 - Women with type 1 diabetes not protected against coronary artery disease
February 20, 2018 - Persistent bloating can be a sign of ovarian cancer, warns charity
February 20, 2018 - Trump administration proposes rule to loosen curbs on short-term health plans
February 20, 2018 - Key protein involved in epigenetic regulation of gene expression guides skin cell renewal
February 20, 2018 - Heart attack symptoms often missed in women
February 20, 2018 - Diagnosis of celiac disease takes 3.5 years for patients who do not report GI symptoms
February 20, 2018 - Study reveals functional dynamics of ion channels
February 20, 2018 - Study explores link between mortality risk and combustible tobacco use
February 20, 2018 - ‘She Trusted Me, and I’d Turned Her Away’
February 20, 2018 - AbbVie and Voyager Therapeutics collaborate to develop new treatments for tauopathies
February 20, 2018 - Fast food makes the immune system more aggressive in the long term
February 20, 2018 - Therapeutic target for glaucoma could have treatment ramifications for Alzheimer’s and Parkinson’s
February 20, 2018 - Overcoming Negative Reviews | Medpage Today
February 20, 2018 - MyD88—villain of allergies and asthma
February 20, 2018 - Food scientists develop rapid screening technique to detect pesticide residue in vegetables
February 20, 2018 - Lab-grown cerebellar cells may help explain how ASD develops at molecular level
February 20, 2018 - Scientists explore connection between bad sleep habits and stiff blood vessels
February 20, 2018 - New Treatment Apalutamide (Erleada) Approved for Prostate Cancer That Resists Hormone Therapy
February 20, 2018 - Do You Really Need My Signature on That?
February 20, 2018 - HIV-1 genetic diversity is higher in vaginal tract than in blood during early infection
February 20, 2018 - Diabetes does not increase work-loss years due to early retirement
February 20, 2018 - Researchers aim to find out how PTSD affects decisions of police
February 20, 2018 - UH Cleveland Medical Center explores novel treatments for uterine fibroids
February 20, 2018 - Flu Vax Efficacy 25% Against Predominant H3N2 Strain So Far
February 20, 2018 - HIV screening most optimal at 25 years of age if no risk factors
February 20, 2018 - Loyola Medicine primary care physician offers advice to minimize risk of flu
February 20, 2018 - Safe sleep recommendations for parents that may help reduce child’s risk of SUID
February 20, 2018 - Why Do So Few Docs Have Buprenorphine Waivers?
February 20, 2018 - Low levels of alcohol good for the brain
February 20, 2018 - Experimental treatment improves invisible symptoms of a man with spinal cord injury
February 20, 2018 - Myriad’s EndoPredict offers better prediction of breast cancer recurrence, analysis shows
February 20, 2018 - Researchers identify fifteen genes that determine our facial features
February 20, 2018 - Morning Break: New Health IT Player; Luxturna No Bargain; Nuclear Freakout
February 20, 2018 - How does it compare? Hospice care at home, at assisted living facility, at nursing home
February 19, 2018 - Scientists develop water-soluble warped nanographene for bioimaging
Genetic Mutation Slows Motor Symptoms in PD

Genetic Mutation Slows Motor Symptoms in PD

image_pdfDownload PDFimage_print

Action Points

  • Parkinson’s disease (PD) patients who carried the leucine-rich repeat kinase 2 (LRRK2) G2019S genetic mutation had slower motor function decline than patients with idiopathic PD, in a seven-year longitudinal follow-up study.
  • Not that while most cases of PD are idiopathic, mutations in the LRRK2 gene are the most common cause of PD in the small percent of cases that are linked to genetics.

Parkinson’s disease (PD) patients who carried the leucine-rich repeat kinase 2 (LRRK2) G2019S genetic mutation had slower motor function decline than patients with idiopathic PD, according to researchers for the LRRK2 Ashkenazi Jewish Consortium.

The annual estimated rate of change in the Unified Parkinson’s Disease Rating Scale (UPDRS) III motor score was less among LRRK2 G2019S carriers than non-carriers: 0.689 versus 1.056, or a difference of −0.367 points (P=0.02), reported Rachel Saunders-Pullman, MD, MPH, of Mount Sinai Beth Israel Medical Center in New York City, and colleagues.

In cognitive change, however, there was no statistically significant difference between PD patients who had the mutation and those who did not, they wrote in JAMA Neurology.

“Although a milder progression in motor symptoms in individuals with PD who carry the LRRK2 G2019S mutation has been posited in cross-sectional studies, the present study is the first, to our knowledge, to demonstrate this milder progression using prospective analysis,” the authors stated. “The slower progression estimates could inform clinical trial design for emerging LRRK2-targeted agents.”

While most cases of PD are idiopathic, a small percent are linked to genetics. Mutations in the LRRK2 gene are the most common cause of PD in this subset. The G2019S mutation of this gene has been linked to PD among people with Ashkenazi Jewish ancestry, among others.

For this longitudinal study, researchers conducted an assessment of PD patients of Ashkenazi Jewish descent from three sites — two in New York City and one in Tel Aviv — from July 21, 2009, to Sept. 30, 2016, excluding patients with glucocerebrosidase (GBA1) mutations and patients who had undergone deep brain stimulation.

Of 545 patients in the study, 26.4% carried the LRRK2 G2019S mutation.

Both groups had similar ages, UPDRS I-III subscale scores, Schwab and England Activity of Daily Living Scale scores, Hoehn and Yahr ratings, and total Montreal Cognitive Assessment (MoCA) scores.

Carriers were more likely to be women (50.0% versus 40.1, P=0.04) and to have postural instability gait disturbance (PIGD, 68.3% versus 55.1%, P=0.02). They also had longer mean duration of disease (8.2 versus 6.3 years, P<0.001) and a higher average daily equivalent dose of levodopa (407.4 versus 337.1 mg, P=0.06).

Using linear mixed-effects models — adjusted for baseline age, sex, site, duration of disease at baseline, MoCA score, and levodopa-equivalent dose — the researchers found that the rate of change in UPDRS III motor score per year was 0.367 points less for LRRK2 G2019S carriers (0.689 points) than non-carriers (1.056 points, P<0.001).

The rate of change in MoCA score per year among LRRK2 G2019S carriers (−0.096 points), however, did not reach statistical significance compared with non-carriers (−0.192 points, P=0.08).

“Our study did show a potentially provocative finding with regard to patients with PD who carry the LRRK2 mutation — namely, slower progression of disease in the setting of a higher frequency of classification as PIGD,” the authors noted. This included a slower decrease in total UPDRS, UPDRS I, UPDRS III, and posture, gait, and balance scores. Moreover, they noted, the difference in the change in UPDRS score remained significant after adjusting for PIGD.

“This population, and others like it, will likely be essential in the early days of finding the first medications to slow or stop the progression of motor and cognitive dysfunction associated with Parkinson’s disease,” said Andrew West, PhD, of the University of Alabama at Birmingham, who was not involved in study.

“We hope that genetically-defined disease will be similar to sporadic disease, and it appears to be true in this case,” he told MedPage Today. “Nominal differences were seen in how fast the disease moves forward, which suggests a slightly bigger group of volunteers than initially anticipated may be needed to find the best drugs.”

Because the researchers did not have extensive follow-up data, they designed this study with linear models. This might limit findings since PD may not have a linear course, especially in its late stage. To address this, the researchers performed a sensitivity analysis on individuals who had PD for 20 years or less; they found the overall association with UPDRS scores held.

Saunders-Pullman and co-authors disclosed no relevant relationships with industry.


last updated

Tagged with:

About author

Related Articles