Breaking News
March 22, 2019 - Alzheimer’s patients using antiepileptic drugs have twice the risk of pneumonia, study shows
March 22, 2019 - Skin diseases may be more prevalent than previously thought
March 22, 2019 - Overall rates of death from breast cancer are falling across the EU
March 22, 2019 - Novel plasmid could hold key to control of mosquito-borne illness
March 22, 2019 - Female Emergency Physicians Paid Less Than Males
March 22, 2019 - Estimated average glucose (eAG): MedlinePlus Medical Encyclopedia
March 22, 2019 - Experimental drug could be new option for type 2 diabetes
March 22, 2019 - Five Things To Know About The Electronic Health Records Mess
March 22, 2019 - TMJ disorders could be treated with tissue-engineered implants after successful animal study
March 22, 2019 - Team-based approach is key to successful care of pregnant women with heart failure
March 22, 2019 - Study identifies gene variant associated with accelerated cellular aging
March 21, 2019 - Salk scientists show how background noise from neurons can interrupt focused attention
March 21, 2019 - New class of drugs could help treat patients diagnosed with ovarian cancer
March 21, 2019 - Tecentriq Approved for Small Cell Lung Cancer
March 21, 2019 - Adipocyte glucocorticoid receptors play a role in developing steroid diabetes
March 21, 2019 - Climate change can affect nutrient content of crops, harming human health
March 21, 2019 - Podcast: KHN’s ‘What The Health’ Surprise! Fixing Surprise Medical Bills Is Harder Than it Looks
March 21, 2019 - Chemistry researchers patent new method for making anti-leukemia compounds
March 21, 2019 - UIC scientists identify hidden proteins in bacteria
March 21, 2019 - New Australian drug trial achieves remarkable results in patients with acute myeloid leukemia
March 21, 2019 - Females live longer when they have help raising offspring
March 21, 2019 - How did orthodontists sell orthodontics?
March 21, 2019 - In the Spotlight: From dietitian to physician assistant student
March 21, 2019 - The CRISPR Revolution: What You Need to Know
March 21, 2019 - FDA Chief Calls For Stricter Scrutiny Of Electronic Health Records
March 21, 2019 - Combined glucocorticoid and antioxidant therapy could benefit premature babies
March 21, 2019 - Low levels of certain eye proteins could serve as predictor for Alzheimer’s
March 21, 2019 - Post-traumatic holocaust survivors transmit negative views on aging to offspring
March 21, 2019 - City of Hope receives $7.5 million in grant awards to study cutaneous T cell lymphoma
March 21, 2019 - New video game-led training device helps stroke survivors regain arm mobility
March 21, 2019 - Compounds in coffee could slow prostate cancer growth
March 21, 2019 - New mobile DNA element in Wolbachia may contribute to improved disease control strategies
March 21, 2019 - Phase 2 Clinical Trial of Bermekimab Shows Potential New Standard of Care for Treatment of Hidradenitis Suppurativa, Including Significant Pain Reduction without Antibiotics
March 21, 2019 - More than one-third of patients risk major bleeding by doubling up on blood thinners
March 21, 2019 - A skeptical look at popular diets: Thumbs up for Mediterranean
March 21, 2019 - PTSD After Cardiac Arrest Predicts More Heart Trouble
March 21, 2019 - Role of immunological imprinting in elicitation of new antibodies
March 21, 2019 - Breast cancer relapse predictor tool may soon be a reality
March 21, 2019 - New computer program developed by TGen lights up cancer-causing genetic mutations
March 21, 2019 - FDA warns two breast implant makers for failure to comply with post-approval study requirements
March 21, 2019 - Butler Hospital receives COBRE grant to enhance research on neuropsychiatric illnesses
March 21, 2019 - Majority of osteoporosis clinical practice guidelines ignore patients’ voices
March 21, 2019 - Generic messages don’t help patients to lose weight
March 21, 2019 - Eisai and Imbrium Therapeutics Announce U.S. FDA Filing Acceptance of New Drug Application for Lemborexant for the Treatment of Insomnia
March 21, 2019 - Two-drug combos using popular calcium channel blocker show superiority in lowering BP
March 21, 2019 - First-in-human pilot study shows positive results for ‘bacteria-phobic’ catheter
March 21, 2019 - Itamar Medical launches next-generation WatchPAT system for home sleep apnea testing
March 21, 2019 - Study estimates health and economic impacts of healthy food prescriptions
March 21, 2019 - Detecting fungal disease in crops with multispectral imaging system
March 21, 2019 - MIT announces creation of the Alana Down Syndrome Center
March 21, 2019 - Next-generation LVAD device clinically superior, safer for heart failure patients
March 21, 2019 - Allergan Announces FDA Approval of Avycaz (ceftazidime and avibactam) for Pediatric Patients
March 21, 2019 - Mutations in noncoding genes could play big role in regulating cancer, study finds
March 21, 2019 - A medical student’s thoughts on Match Day
March 21, 2019 - Are eggs good or bad for you?
March 21, 2019 - New analysis reveals precision oncology insights for colorectal cancer
March 21, 2019 - Pollutants appear to weaken immune system and increase pathogen virulence
March 21, 2019 - Researchers develop and validate scale for rating severity of mononucleosis
March 21, 2019 - Scientists identify generation of key immune response in mice on introducing solid food
March 21, 2019 - New nanomaterial could restore internal structure of damaged bones
March 21, 2019 - Selective destruction of prostate tumor as effective as complete prostate removal
March 21, 2019 - 2011 to 2015 Saw Increase in Psychiatric ED Visits for Youth
March 21, 2019 - Tapeworm drug targets common vulnerability in tumor cells
March 21, 2019 - WVU researcher discovers higher suicide rate among Medicaid-insured youth
March 21, 2019 - Off the beaten path for global health residency
March 21, 2019 - European Parliament’s report calls on EU to develop policies to regulate endocrine-disrupting chemicals
March 21, 2019 - Women with undiagnosed diabetes in pregnancy more likely to experience stillbirths
March 21, 2019 - Fish consumption can help prevent asthma, study reveals
March 21, 2019 - Royal Holloway professors to lead new to research into curing Neurofibromatosis type 1
March 21, 2019 - NSF offers grant to improve treatment approaches for pelvic organ prolapse
March 21, 2019 - Your Apple Watch Might Help Spot a Dangerous Irregular Heartbeat
March 21, 2019 - Research team uncovers critical new clues about what goes awry in autistic brains
March 21, 2019 - From March Madness to medicine with help from mentors
March 21, 2019 - Mental health disorders among young adults may be on the increase
March 21, 2019 - New study examines smarter automatic defibrillator
March 21, 2019 - UC Riverside research shows how natural selection favors cheaters
March 21, 2019 - Mother’s diet during pregnancy can impact lung-specific genes of her offspring
March 21, 2019 - AeroForm Tissue Expanders makes breast reconstruction after mastectomy more comfortable
March 21, 2019 - New project focuses on creating more responsive, intuitive prosthetics
March 21, 2019 - New case study describes adolescent patient with rapid-onset schizophrenia and Bartonella infection
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