Breaking News
January 16, 2019 - Persistent Opioid Use High in Head, Neck Cancer Patients
January 16, 2019 - Questions to ask your doctor about post pregnancy care: MedlinePlus Medical Encyclopedia
January 16, 2019 - Neurons with good housekeeping are protected from Alzheimer’s
January 16, 2019 - Is mindfulness worthy of all the hype?
January 16, 2019 - Physical Activity, Any Type or Amount, Cuts Health Risk from Sitting
January 16, 2019 - New understanding in the evolution of human feet
January 15, 2019 - AHA: New Cholesterol Guidelines Put Ethnicity in the Spotlight
January 15, 2019 - Different brain areas linked to smoking and drinking
January 15, 2019 - Henry Marsh shares insights into neurosurgery and more at Dean’s Lecture Series
January 15, 2019 - Want to Live Longer? For Just 30 Minutes a Day, Do Anything Else But Sit
January 15, 2019 - The Current issue of “The view from here” is concerned with Targets
January 15, 2019 - Plain packaging sparked tobacco price rises, new study finds
January 15, 2019 - Sedentary lifestyles can be unhealthy, physical activity can lower risk
January 15, 2019 - Gut microbiome may help prevent development of cow’s milk allergy
January 15, 2019 - Lesbian, gay and bisexual individuals more likely to suffer severe substance use disorders
January 15, 2019 - New England Journal of Medicine Publishes Positive Results of the Pivotal Trial of Cablivi (caplacizumab) for Rare Blood Clotting Disorder
January 15, 2019 - Levels of inflammatory marker (CRP) linked to housing type and tenure
January 15, 2019 - Three gifts I’m glad I gave myself in 2018
January 15, 2019 - Columbia’s Pediatrics Department Names New Vice Chairs, Expands Leadership
January 15, 2019 - US FDA Accepts Regulatory Submissions for Review of Tafamidis to Treat Transthyretin Amyloid Cardiomyopathy
January 15, 2019 - Staying fit can cut your risk of heart attack by half
January 15, 2019 - Vitamin D supplements are of no gain to those over 70, study shows
January 15, 2019 - Scientists create comprehensive new method to predict breast cancer risk
January 15, 2019 - Research shows connection between social media use and impaired risky decision-making
January 15, 2019 - FDA Approves Expanded Use of Adacel (Tdap) Vaccine for Repeat Vaccination
January 15, 2019 - Treating spinal pain with replacement discs made of ‘engineered living tissue’ moves closer to reality
January 15, 2019 - Providers Walk ‘Fine Line’ Between Informing And Scaring Immigrant Patients
January 15, 2019 - Outcomes Poorer for Medicaid Beneficiaries With STEMI
January 15, 2019 - Decorative Products on Foods Can Be Unsafe
January 15, 2019 - A dream of sustainable surgery in Uganda
January 15, 2019 - Study shows how herpes viruses and tumors have learned to manipulate the same ancient RNA
January 15, 2019 - Common Heart, Diabetes Meds May Help Ease Mental Illness
January 15, 2019 - Stress and trauma in earliest years linked to reduced hippocampal volume in adolescence
January 15, 2019 - Scientists identify endogenous activator of sigma-1 receptors in human cells
January 15, 2019 - MAR treatments unlikely to be cause of premature or low birth weight babies
January 15, 2019 - Parental CPTSD increases transmission of trauma to offspring of Tutsi genocide survivors
January 15, 2019 - High-fat diets shown to increase blood pressure
January 15, 2019 - New institute for food safety to be established in Netherlands
January 15, 2019 - Keele University researchers receive £2.4 million grant to help reduce overprescribing of opioids
January 15, 2019 - Synthetic compound reverses mutant p53 aggregate accumulation, study shows
January 15, 2019 - First elder care robot tested in a WSU smart home apartment
January 15, 2019 - Oxford researchers explore relationship between technology use and adolescent mental health
January 15, 2019 - From microbiome research to healthier and sustainable foods
January 15, 2019 - How coaching moms and dads improves infants’ language skills
January 15, 2019 - Precision health approach tapped to identify causes of poverty
January 14, 2019 - DNA origami can accurately measure how antibodies interact with several antigens
January 14, 2019 - Researchers identify multiple new subtypes of most common childhood cancer
January 14, 2019 - Total Fertility Rates Vary by State
January 14, 2019 - Elevated blood lead level in early childhood associated with increased risk of academic problems in school-aged children
January 14, 2019 - Superior technique identified that can block CRISPR gene editing
January 14, 2019 - Turning breast cancer cells into fat cells prevents the formation of metastases
January 14, 2019 - Review examines what influences HIV-positive patients to stay on antiretroviral drugs in Africa
January 14, 2019 - Identifying genetic factors that lead to squamous cell carcinoma
January 14, 2019 - Virtual video visits can replace office visits without compromising quality of care
January 14, 2019 - Health Highlights: Jan. 10, 2019
January 14, 2019 - Molecular hallmarks of tumor hypoxia across 19 cancer types discovered
January 14, 2019 - Scientists uncover how protein clumps damage cells in Parkinson’s
January 14, 2019 - Physician-scientist’s “indomitable spirit” prevails over personal adversity
January 14, 2019 - King’s researchers receive £1.25 million to investigate fatal eating disorder
January 14, 2019 - UCR researchers uncover how plants sense temperature
January 14, 2019 - Scientists find link between colitis and colon cancer
January 14, 2019 - New skin patch provides long-acting contraceptive protection
January 14, 2019 - Asparagine synthetase deficiency – Genetics Home Reference
January 14, 2019 - Improved stem cell approach could aid fight against Parkinson’s
January 14, 2019 - New class of sleeping pill preserves ability to wake in response to danger signals
January 14, 2019 - Cancer patients are four times more likely to commit suicide
January 14, 2019 - The human brain works in reverse order to retrieve memories
January 14, 2019 - Simple tips can lead to better food choices
January 14, 2019 - Meth’s Resurgence Spotlights Lack Of Meds To Combat The Addiction
January 14, 2019 - TARA Biosystems and Insilico Medicine collaborate to discover novel therapies for cardiac disease
January 14, 2019 - Early life stress in mice affects their offspring behavior
January 14, 2019 - Depression Tied to Worse Asthma Outcomes in Urban Teens
January 14, 2019 - Santa calorie counting
January 14, 2019 - Opiod prescriptions for pet dogs misused by their masters
January 14, 2019 - People with ASD could be better at recognizing regret and relief in others finds study
January 14, 2019 - Conducting ChIP-Seq with Low Cell Numbers
January 14, 2019 - Study explores support and social networks of family carers of people with dementia
January 14, 2019 - At Risk for an Opioid OD? There’s an App for That
January 14, 2019 - Single national electronic health record will help improve care in Canadian hospitals
January 14, 2019 - Study unearths Britain’s first speech therapists
Newly discovered compound shows potential for treating Parkinson’s disease

Newly discovered compound shows potential for treating Parkinson’s disease

image_pdfDownload PDFimage_print

A joint research group centered around Professor Hideyuki Okano and Associate Professor Jun Kohyama, Department of Physiology of the Keio University School of Medicine, together with a research group of Eisai Co., Ltd. has identified a compound that has the potential to be a treatment for Parkinson’s disease by using dopaminergic neurons differentiated from induced pluripotent stem (iPS) cells from patients with familial Parkinson’s disease.

Aiming to develop treatments for Parkinson’s disease, this research group utilized neural progenitor cells induced from iPS cells derived from patients with familial Parkinson’s disease and established a differentiation protocol for the stable supply of a large number of dopaminergic neurons. Furthermore, the research group screened an existing drug library as an indicator of susceptibility to stress observed in dopaminergic neurons derived from Parkinson’s disease patients, and identified compounds that inhibit calcium channels. Further detailed analysis conducted by the research group revealed higher expression of T-type calcium channels in dopaminergic neurons derived from PARK2 patients. It was also found that apoptosis of dopaminergic neurons derived from Parkinson’s disease patients could be reduced by inhibiting calcium influx via T-type calcium channels.

From these results, it is suggested that combining disease specific iPS cells and existing drug library has potential for both the development of treatments and clarification of disease pathology.

The results of this research was published in the online version of Stem Cell Reports at 12:00 noon on October 18, 2018 (EST).

Background and Outline of Research

Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease, and causes motor symptoms such as tremor, bradykinesia, rigidity and postural instability and autonomic dysfunction due to a preferential loss of dopaminergic neurons in the substantia nigra. For 90% of Parkinson’s disease patients, symptoms are idiopathic and it is difficult to understand the relationship between various factors, including those associated with the environment, and the disease mechanism. However, approximately 10% of patients show the familial incidence of Parkinson’s disease, therefore understanding the disease mechanism for familial Parkinson’s disease may also link with the understanding of Parkinson’s disease including idiopathic Parkinson’s disease as well as drug development.

Through the use of iPS cell technologies developed by Professor Shinya Yamanaka of Kyoto University in 2006, research has made great advances even in diseases that were difficult to be investigated by conventional methods. In 2012, the Keio University School of Medicine became the first research facility in Japan to create iPS cells from patients with familial Parkinson’s disease, and was successful in replicating the disease mechanism. Currently research into neurological diseases has become very active throughout the world, and the understanding of diseases and development of new treatments is highly anticipated.

In April 2013, the Keio University School of Medicine and Eisai initiated the “Innovative Drug Discovery Project for Refractory Neurological Diseases Using iPS Cell Technologies,” and since then this drug discovery project has been progressing as an industry-academia collaboration, making full use of Keio University School of Medicine’s iPS cell and related technologies as well as Eisai’s drug discovery techniques. Through this research, dopaminergic neurons which are thought to be damaged in Parkinson’s disease patients are created efficiently and easily using iPS cells derived from Parkinson’s disease patients, and an experimental system for conducting screening for drug discovery was established. In this research, Keio University School of Medicine’s library of over 1,000 existing drugs was screened to find compounds preventing increased susceptibility to stress in dopaminergic neurons derived from Parkinson’s disease patients.

Results and Significance of Research, Future Development

In this research, neural progenitor cells induced from iPS cells established from two familial Parkinson’s disease (PARK2) patients were used to efficiently generate dopaminergic neurons. In patient-derived neurons, reduced neurite length as well as elevated oxidative stress and apoptosis were observed compared to neurons derived from healthy controls. Furthermore, it was revealed that these disease-relevant phenotypes were also observed in dopaminergic neurons derived from isogenic PARK2 null iPS cells obtained by genome editing.

In addition, since patient-derived dopaminergic neurons showed high susceptibility to rotenone, a mitochondrial respiratory chain complex I inhibitor, an existing drug library was screened with vulnerability to this drug-induced stress as the target. From phenotypic screening with an existing drug library, several compounds that suppressed stress-induced apoptosis were identified. Furthermore, it was found that T-type calcium channel antagonists effectively reduced stress-induced apoptosis. Importantly, these compounds demonstrated similar reduction in stress-induced apoptosis in dopaminergic neurons derived from other type of familial Parkinson’s disease (PARK6) patients who possess a genetic abnormality which is different to PARK2.

Further detailed analysis conducted by the research group revealed higher expression of T-type calcium channels in dopaminergic neurons derived from PARK2 patients. It was also found that apoptosis of dopaminergic neurons derived from Parkinson’s disease patients could be reduced by inhibiting calcium influx via T-type calcium channels.

From these results, using iPS cells derived from patients enabled the establishment of in vitro disease models that reflect human biology, and by further combining with existing drug library, suggested efficacy for drug screening. By promoting the understanding of disease pathology through this method, it is hoped that this will lead to application in the development of a fundamental treatment for Parkinson’s disease. Going forward, this research will continue, the knowledge gained will be further developed, and experimental systems closely reflecting the brain environment in vivo such as co-cultured neurons with glial cells will be utilized in an effort to verify the validity of targets for Parkinson’s disease.

Source:

https://www.eisai.com/news/2018/news201887.html

Tagged with:

About author

Related Articles