Breaking News
September 25, 2018 - Study provides evidence of beta lactamase producing, antimicrobial resistant E. coli in U.S. retail meat
September 25, 2018 - UCI study finds new cause of cerebral microbleeds
September 25, 2018 - Researchers propose mechanism by which ASTN2 protein defects lead to brain disorders
September 25, 2018 - Chinese and German researchers to cooperate more closely in future for better food
September 25, 2018 - Recent study helps predict probability of pregnant mothers to have child with autism
September 25, 2018 - New online, sound matching tool offers tinnitus sufferers potential treatment options
September 25, 2018 - UC Davis researchers take critical step in developing more effective Salmonella vaccine
September 25, 2018 - Antibiotics best paediatric treatment for children’s chronic wet cough
September 25, 2018 - Looking beyond opioids: Stanford pain psychologist briefs Congress
September 25, 2018 - Organs actively fighting back against autoimmune diseases, finds study
September 25, 2018 - Lancaster professor aims to understand how genes affect smoking cessation
September 25, 2018 - Human-oriented perspective needed to better understand Parkinson’s disease
September 25, 2018 - Physical activity may have beneficial effects for people with rare Alzheimer’s disease
September 25, 2018 - FDA Updates on Valsartan Recalls
September 25, 2018 - 3-D-printed tracheal splints used in groundbreaking pediatric surgery
September 25, 2018 - Who is the designated driver, or proxy, for your health decisions?
September 25, 2018 - New chemo-optogenetic method enables multi-directional activity control of cellular processes
September 25, 2018 - Study explores link between genetic predisposition to Alzheimer’s and cardiometabolic risk factors
September 25, 2018 - NeoTract presents new clinical data from studies of UroLift System for patients with BPH
September 25, 2018 - Statins Improve Long-Term Survival After AAA Repair
September 25, 2018 - Novel brain network linked to chronic pain in Parkinson’s disease
September 25, 2018 - Researchers reassess negative pressure wound therapy as its benefit and harm remain unclear
September 25, 2018 - Older adults with ‘fall plan of care’ less likely to suffer fall-related hospitalizations
September 25, 2018 - FDA lifts partial clinical hold that paused enrollment of new patients in tazemetosta clinical trials
September 25, 2018 - IME Medical Electrospinning establishes state-of-the-art manufacturing lab facilities
September 25, 2018 - Phase 1 and 2 clinical trials of entrectinib drug in ROS1-positive NSCLC show promising results
September 25, 2018 - How to Protect Your Eyesight
September 25, 2018 - Novel approach allows researchers to define how cells in the retina respond to diabetes
September 25, 2018 - Columbia University announces winners of 2018 Louisa Gross Horwitz Prize
September 25, 2018 - Clinical trial investigators found non-compliant with requirement to report results on EU register
September 25, 2018 - Study analyzes quality of protein supplements in function of source, treatment and storage
September 25, 2018 - FDA grants Orphan Drug Designation to Myelo001 for treatment of Acute Radiation Syndrome
September 25, 2018 - U.S. Alzheimer’s Cases to Nearly Triple by 2060
September 25, 2018 - Improving cell replacement therapy for Parkinson’s disease
September 25, 2018 - Genervon reports new findings that drug candidate GM6 attenuates Alzheimer’s disease in mice model
September 25, 2018 - FDA approves new 5 mm diameter drug-eluting stent from Cook Medical
September 25, 2018 - New $17.8 million grant ensures USC at forefront of research on tobacco-related health risks
September 25, 2018 - Researchers analyze response to combination immunotherapy for patients with rare skin cancer
September 25, 2018 - Study sheds light on how brain protein may be involved neurodevelopmental disorders
September 25, 2018 - Where to draw the line on incentives
September 25, 2018 - Solid fuel use linked with increased risk of hospitalization or death from respiratory diseases
September 25, 2018 - ‘Trouble Brewing’ report highlights steps that governments can take to reduce alcohol-related harms
September 25, 2018 - Recurrence risk of VTE appears similar for patients with cancer and those with unprovoked VTE
September 25, 2018 - Global leaders must make bold commitments at first-ever UN tuberculosis summit
September 25, 2018 - Brief sleep intervention works long-term to prevent child obesity
September 25, 2018 - Vaping among kids and teens a growing concern
September 25, 2018 - Public launch of products and application solutions from Porvair Laboratory Division
September 25, 2018 - Harmful H. pylori may play a role in Parkinson’s disease
September 25, 2018 - Researchers develop way to measure different types of fear of falling in patients with Parkinson’s
September 25, 2018 - Fracture causes bone density losses throughout the body
September 25, 2018 - Researchers highlight potential therapy for treating rare, deadly blood-clotting disorder
September 25, 2018 - Hybrid theranostic complex shows high therapeutic efficacy against tumor cells
September 25, 2018 - FDA Issues Statement Reaffirming the Positive Benefit-Risk Profile of Nuplazid (pimavanserin) for Patients with Hallucinations and Delusions Associated with Parkinson’s Disease Psychosis
September 25, 2018 - Toxicological evaluation and dosimetry estimation of potential PET radiotracer
September 25, 2018 - 5 obstacles parents commonly face in child obesity treatment and how to overcome them
September 25, 2018 - Immunologist to study how Chikungunya causes devastating effects in older adults
September 25, 2018 - Rural borderland communities vulnerable to high stress impacting mental and physical health
September 25, 2018 - SNMMI announces recipients of 2018-2020 Wagner-Torizuka Fellowship
September 25, 2018 - Common painkiller not effective in controlling chronic pain after traumatic nerve injury
September 25, 2018 - New therapeutic vaccine helps immune cells fight HPV-related head and neck cancer
September 25, 2018 - Environmentally-induced gene activity influences IQ test performance
September 25, 2018 - Biogen and Eisai announce results of LTE Phase 1b study of aducanumab for treating MCI
September 25, 2018 - FDA Approves Copiktra (duvelisib) Capsules for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Follicular Lymphoma
September 25, 2018 - Medical device company settles US case over false claims
September 25, 2018 - Trying to get answers: One woman’s quest for a diagnosis
September 25, 2018 - Lung cancer patients treated with invasive surgery more likely to become chronic opioid users
September 25, 2018 - Oxford VR raises £3.2m to boost innovation in VR for mental health problems
September 25, 2018 - Gene therapy approach could help treat mitochondrial diseases
September 25, 2018 - Few Yogurt Products Qualify As Low-Sugar
September 25, 2018 - Eye disease can cause blindness, and it’s on the rise
September 25, 2018 - Pawnshop density linked to gun-related suicides, Stanford study finds
September 25, 2018 - Pioneering procedure for common prostate condition offered by The London Clinic
September 25, 2018 - Number of people with respiratory diseases likely to increase if UK air pollution remains unchecked
September 25, 2018 - FARXIGA receives positive results in Phase III DECLARE-TIMI 58 cardiovascular outcomes trial
September 25, 2018 - New program to reduce harmful stress effectively improves mood in cancer patients
September 24, 2018 - Florence’s Lingering Threat: Mold – Drugs.com MedNews
September 24, 2018 - For professional baseball players, faster hand-eye coordination linked to batting performance
September 24, 2018 - Bill for later school start times is defeated, but Stanford sleep specialist isn’t
September 24, 2018 - For Heart Failure Patients, Mitral Valve Procedure Improved Outcomes
September 24, 2018 - Successful recovery from addiction means more than achieving abstinence
New therapeutic approach may delay neurodegeneration in rare genetic disease

New therapeutic approach may delay neurodegeneration in rare genetic disease

image_pdfDownload PDFimage_print

A new therapeutic approach may one day delay neurodegeneration typical of a disease called mucopolysaccharidoses IIIB (MPS IIIB). Neurodegeneration in this condition results from the abnormal accumulation of essential cellular molecules called mucopolysaccharides. Looking to find alternative therapeutic strategies for this rare genetic disease, a team of researchers investigated whether enhancing the cells’ ability to clear accumulation of cellular waste would help eliminate the abnormal storage of mucopolysaccharides. They report in the journal Autophagy that the sugar trehalose increases cellular waste disposal and improves the neurological symptoms in a mouse model of the disease.

“MPS IIIB is one of about 50 lysosomal storage disorders characterized by the accumulation of material inside tiny cellular sacs called lysosomes,” said corresponding author Dr. Marco Sardiello, assistant professor of molecular and human genetics and a member of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and Baylor College of Medicine. “In the case of MPS IIIB, a mutation on a gene that codes for a lysosomal enzyme that breaks down a cellular material called heparan sulfate, renders the enzyme ineffective. Consequently, the lysosome cannot do its work of degrading heparan sulfate to either discard it or recycle it, and the material accumulates.”

Over the years, accumulation of heparan sulfate in lysosomes leads to degeneration of brain tissue. Although infants appear healthy at first, they slowly begin to show behavioral problems, hyperactivity, aggressiveness, sleep disturbances and loss of vision and hearing. Later in life, they become immobile and develop swallowing difficulties. Usually, they don’t live past the second decade. Current strategies being tested for the treatment of this condition in animal models include attempting to correct the enzyme deficiency by providing a fully working enzyme. However, this approach faces challenges such as having limited ability to cross the blood-brain barrier and reaching the brain areas where the enzyme is needed.

A non-traditional approach

“We explored a way to treat this condition with a nontraditional approach,” Sardiello said. “We recently discovered that the small sugar trehalose promotes the recycling of cellular waste. This made us think of an indirect approach to try to solve the accumulation of heparan sulfate. Instead of correcting the enzyme deficiency, we would try to overcome it by enhancing the cells’ natural ability to discard cellular waste.”

The researchers tested their approach on a mouse model of MPS IIIB. These mice have a mutation that results in the recapitulation of most of the clinical symptoms observed in patients, including progressive neurodegeneration, loss of vision, brain inflammation and shorter lifespan.

One group of MPS IIIB mice received trehalose in the drinking water, while another group of MPS IIIB mice did not receive the sugar. As controls, normal mice without the mutation were provided water with or without trehalose. The researchers observed the animals for 11 months, taking samples at the middle and at the end of the observation period.

“The results were highly encouraging,” said first author Dr. Parisa Lotfi, postdoctoral associate in the Sardiello lab. “The MPS IIIB mice treated with trehalose lived longer, improved their hyperactive behavior and delayed several neuropathological features, most notably the retinal degeneration, when compared with MPS IIIB mice not treated with trehalose.”

In addition, the researchers explored the molecular mechanism underlying the trehalose effect.

“Previously, we had discovered that trehalose activates TFEB, a master regulator of the lysosomal system. As the activity of TFEB increases, the degradation and clearance of molecules in the lysosomes becomes more efficient,” said Lotfi. “Here, we were the first to quantify the amount of trehalose that crosses the blood-brain barrier and activates TFEB in the brain. In turn, TFEB activated the lysosomal system, which led to enhanced clearance of material accumulation, reduced neuroinflammation, retinal degeneration and vision loss and extended lifespan.”

This study is the first to show that trehalose is acting through TFEB but no other molecules. Also, this is the first preclinical study showing that it is possible to delay retinal degeneration and loss of vision in a mouse model of MPS IIIB.

“The effect on the retina is important,” Lotfi said. “Loss of vision is one of the most devastating aspects of some lysosomal diseases. In animal models, treatments based on enzyme replacement therapy do not reach the brain and do not counteract loss of vision. We think that in the future our strategy can potentially be used either as the main therapy or complementary to other therapies.”

“Our results encourage us to consider that trehalose also may be effective in other lysosomal storage diseases, such as Batten disease,” Sardiello said. “Trehalose is a widely used food additive with no current restrictions for human use.”

Source:

https://www.bcm.edu/news/molecular-and-human-genetics/simple-sugar-delays-type-of-neurodegeneration

Tagged with:

About author

Related Articles