Day 2 :
Keynote Forum
Robert W Ledeen
New Jersey Medical School, USA
Keynote: Deficiency of GM1 ganglioside as major risk factor for idiopathic Parkinson’s disease: Restoration of GM1-GDNF interaction in GM1 replacement therapy for PD mouse
Time : 10:00-10:40
Biography:
Robert Ledeen completed his PhD at the age of 25 years at Oregon State University and postdoctoral studies at the University of Chicago and Albert Einstein College of Medicine. He is the director of Division of Neurochemistry and a Neuroscience professor at Rutgers, New Jersey Medical School. He has published more than 179 papers, book chapters and review articles in reputed journals and has served as an editorial board member on a number of journals.
Abstract:
Several investigators have employed GM1 ganglioside to treat animal models of Parkinson’s disease (PD), and a recent clinical trial showed PD patients treated with GM1 had lower UPDRS motor scores than at baseline after 120 weeks. Our studies of mice with disrupted B4galnt1 gene demonstrated PD symptoms due to deficiency of ganglio-series gangliosides. Both knockout and heterozygous (HT) mice showed depletion of striatal dopamine (DA), loss of TH+ nigral neurons, and aggregation of alpha-synuclein. These manifestations of parkinsonism were largely alleviated by LIGA20, a membrane permeable analog of GM1, and also by GDNF (via AAV2), essential for survival of catecholaminergic neurons. Immunohistochemical analysis of substantia nigra sections revealed significant GM1 deficiency in TH+ nigral neurons of PD patients. Study of the occipital cortex and colon tissue also revealed significantly lower GM1 in PD, suggesting systemic GM1 deficiency as risk factor in idiopathic PD (Hadaczek et al. 2014). That study demonstrated GM1 association with GFRα1 and Ret, components of the GDNF receptor, and GM1 essentiality for cohesion of those receptor proteins. Nigral neurons of PD brain showed deficient GDNF signaling. We propose the above HT mouse with partial GM1 deficiency (similar to PD) as an especially useful PD model in reflecting its actual pathophysiology. This is supported by detection of 3 non-movement disorders in HT mice characteristic of PD: (a) gastrointestinal pathology (constipation), (b) cardiac sympathetic denervation, and (c) cognitive impairment. These too were alleviated by LIGA20, further suggesting the utility of GM1 and especially its membrane permeable analogs for GM1 replacement therapy.
Keynote Forum
George Stoica
Texas A&M University, USA
Keynote: Impact of myosin 5a mutation in neurodegenerative disorders. Rat model
Time : 10:40-11:20
Biography:
George Stoica is a DVM, MSc and a PhD degree holder. He is a Professor in the Department of Veterinary Pathobiology at Texas A & M University, USA. He received his Master’s degree in Veterinary Pathology from Ohio State University and PhD in Experimental Pathobiology from Michigan State University. He has been with Texas A&M University since 1984 and was advanced to Full Professor in 1996. His area of expertise is in experimental neuropathology and his area of research span from chemical carcinogenesis, viral carcinogenesis, comparative neuro-oncology and neurodegenerative disorders in animal models. He published over 100 scientific articles in peer reviewed journals and wrote several chapters in various books.
Abstract:
Myosin5a (Myo5a) is an actin-dependent motor protein that is highly expressed in the brain, and involved in vesicular organelles transport and its absence leads to movement disorders in humans and animal species (Griscelli and Elejalde syndromes in humans), rodents (dilute lethal phenotype in mice, and dilute-opisthotonus of Wistar rats), and Arabian horses Lavender Foal Syndrome. A spontaneous autosomal recessive rat model for neurodegeneration caused by a mutation in the Myo5a gene was developed in our laboratory. The pleiotropic effects of this mutation affect the coat color, central nervous and neuroendocrine systems. Preliminary data from our model of Myo5a mutant Berlin-Druckrey (BD-IV) “shaker” rat demonstrated marked alterative changes involving the alpha-synuclein overexpression, decrease dopamine (DA) levels, alteration of DA metabolism, and overexpression of tau protein in anatomical areas of brain. A significant increased in miR-132 and a decreased in downstream target nuclear receptor 1 protein (Nurr1) was found in affected rats. Nurr1 decrease correlates with decrease of tyrosine hydroxylase and brain-derived neurotrophic factor. The movement disorder and alterative biochemical changes increased in severity after 15 days postnatal. These biochemical changes were not previously reported to be associated with Myo5a mutation. Similar neurological alterative changes are common in human neurodegenerative diseases such as Alzheimer, Parkinson’s Diseases, and Lewis Body dementia, and raised the potential involvement of Myo5a alteration in these neurological diseases, which can lead to translational studies. The challenge will be to investigate the molecular mechanisms of Myo5a and its interaction with other proteins underlying its functions.
- Novel Insights and Therapeutics for Parkinsons Disease
Location: Raume / Room - 4
Chair
Kjell Fuxe
Karolinska Institutet, Sweden
Session Introduction
Micheal Ugrumov
Institute of Developmental Biology RAS, Russia
Title: Neuroplasticity in the nigrostriatal system of MPTP-treated mice at presymptomatic and early symptomatic stages of Parkinsonism
Time : 11:40-12:10
Biography:
Michael Ugrumov, academician of Russian Academy of Sciences has completed his MD at Institute of Evolutionary Physiology & Biochemistry (Leningrad), PhD at Institute of Developmental Biology, Professorship at University Medical School (Moscow). Head of Laboratory of Neural and Neuroendocrine Regulations at Institute of Developmental Biology RAS, Vice-President of Russian Physiological Society. Member of European Academy of Science and Arts, Serbian Academy of Science and Arts, French National Academy of Pharmacy. He has published more than 200 papers in peer reviewed journals and served as an editorial board member of 8 International and Russian journals.
Abstract:
Parkinson’s disease (PD) is characterized by a long development at preclinical (asymptomatic) stage and the first appearance of motor dysfunctions at a loss of most dopaminergic (DA-ergic) neurons, nigral cell bodies and striatal axons, and a depletion of 60-70% DA in the striatum. The goal of this study was to search mechanisms of neuroplasticity serving to prevent motor dysfunctions at presymptomatic stage and the triggers of a transition to symptomatic stage evaluating DA synthesis (tyrosine hydroxylase (TH) mRNA, protein, activity), release (microdialysis in vivo, slices), uptake (slices), degradation (MAO mRNA, activity) at original models. At presymptomatic stage motor dysfunctions were prevented due to plasticity of survived DA-ergic neurons that was manifested by enhanced TH activity, increased spontaneous and stimulated release of DA, and decreased MAO B activity. Noteworthy, striatal DA was synthesized not only in DA-ergic axons but also in non-dopaminergic neurons containing individual enzymes, TH or aromatic L-amino acid decarboxylase, in cooperation. At symptomatic stage, despite maintaining of DA synthesis in DA-ergic neurons at the control level and an increase of DA synthesis in monoenzymatic neurons, intercellular level of DA dropped up followed by an appearance of motor disorders. Major triggers of motor dysfunctions appeared to be a decrease of spontaneous and stimulated release of striatal DA and an increase of MAO A activity. PD models of preclinical and early clinical stages, specified in this study are suitable for development of preventive pharmacotherapy serving to improve compensatory processes and inhibit triggers of motor dysfunctions.
Geeta Shroff
Nutech Mediworld, India
Title: Use of human embryonic stem cells in the treatment of Parkinson’s disease
Time : 12:10-12:40
Biography:
Geeta Shroff has developed the technology to isolate Human Embryonic Stem Cells (hESC), culture them, prepare them for clinical application and store them in readyto- use form with a shelf life of six months. Since 2002, more than 1300 patients suffering from various conditions like spinal cord injuries, diabetes, multiple sclerosis, Parkinson’s disease, cardiac conditions, cerebral palsy have been treated by her. She is a Graduate in Medicine from the University of Delhi and did her Postgraduation in Gynaecology & Obstetrics. She further specialized in treating Infertility and is a Trained Embryologist and a qualified IVF practitioner. After gaining 8 years of valuable clinical experience at Safdarjung Hospital & Batra Hospital, she set up her own IVF practice in 1996. She has begun research on human embryonic stem cells in 1999 and pioneered in human embryonic stem cell therapy. She has presented her work at various national and international forums.
Abstract:
Parkinson’s disease (PD) is a disorder of central nervous system characterized by rigidity, tremor and hypokinesia. Pharmacological and non-pharmacological methods do not improve the quality of life permanently. We used Human Embryonic Stem Cells (hESCs) to treat a 65-year old male patient with PD. Patient had back and neck stiffness, resting tremors, bradykinesia, muscle rigidity, unclear speech and imbalanced walking. SPECT scan showed moderate hypoperfusion in bilateral parieto-temporal regions and moderate-to-severe hypoperfusion in bilateral basal ganglia and bilateral cerebellar regions. hESCs were cultured and maintained in a GMP, GLP and GTP compliant laboratory using patented technology. Safety and efficacy of these hESCs is established. Treatment consisted of four phases (T1, T2, T3 and T4) with gap phases. hESCs were given through i.v. (1 ml twice a week), i.m. (0.25 ml twice daily), supplemental routes (1-5 ml every week) and via nasal sprays (3.5 ml twice a week). After 12 months of therapy, patient showed remarkable improvement in health with reduction in tremors, muscle rigidity, bradykinesia and stiffness in neck, shoulder and low back pain. Patient experienced reduction in apathy in left hand and legs and was able to balance himself while walking. He was able to speak louder. SPECT scan and MRI showed normal hypoperfusion in the cerebral region of the patient. No adverse event and teratoma formation was observed. Patient is being followed up regularly and is taking no medications. He has mild tremor in right hand. hESC therapy benefitted our patient with PD but further studies are needed to gather more evidence.
Audun Myskja
Norges Parkinson for bund, Norway
Title: Evaluation of a rhythmic exercise program for patients with Parkinson’s disease
Time : 13:30-14:00
Biography:
Audun Myskja is a Doctor, Music Therapist, Leader and Founder of ‘Senter for Livshjelp’ (LifeAid Centre for empowerment). His career has encompassed not only allopathic medicine (since 1981) but he has also gained considerable recognition in Norway and other countries for his work in a number of complementary therapies. He worked in general practice and internal medicine during 1982-1998; was educated in complementary therapies and integrated medicine from 1974; and practiced with, healing, herbs and flower essences from 1976. He is an Author for 20 books and 100+ articles on integrated medicine, medical music therapy, self-development, ecology, spirituality, meditation, exercise, health building. He is a Collaborator with Norwegian Parkinson`s disease Association from 2002.
Abstract:
Objective: To evaluate a structured training program using a series of rhythmic exercises for a group of patients with Parkinson’s Disease (PD). Background: There is increasing interest in the potential benefit of systematic exercise in the management of PD. However, there is still insufficient knowledge about what type of exercise may be most beneficial for which symptoms and how exercise programs may be best applied to aid PD patients. Methods: PD patients (n=20) were recruited in a Norwegian region with patients on waiting list as controls. The group followed a structured program with rhythmic exercises once a week led by physiotherapist. The mean age was 62.4 (SD 7.3) years and the mean disease duration was 8 (SD 5.2) years. Participants were evaluated by UPDRS, Hoehn & Yahr, Senior Fitness, Up and Go before project start at 6, 12 and 18 months. Quality of life issues were evaluated by interactive qualitative interviews, Montgomery- Aasberg depression rating scale and Herth Hope Index before project start at 6, 12 and 18 months. Results: Functional tests showed stability in the exercise group compared to control group. Quality of life measures showed low values for depression compared to control group and emphasized the value of group training and the importance of collaboration with participants responses. Interview data suggest that a higher rate of follow-up on home training would further improve results. Conclusions: Our follow-up data from the 4 year period 2011-15 suggest benefit of a rhythmic exercise program developed in collaboration with participants, effects becoming more marked over time. Further research to specify benefits of structured exercise is recommended.
Sanjay Jaiswal
Jaiswal Hospital and Neuro Institute, India
Title: Dyskinesia associated with old and new therapies in Parkinson’s disease
Time : 14:00-14:30
Biography:
Sanjay Jaiswal has completed his MD from RNT Medical College, Udaipur, India and DM Neurology from Institute of Medical Sciences BHU, Varanasi, India. He is a Consultant Neurologist at Jaiswal Hospital and Neuro Institute, Kota, Rajasthan, India. He has published several papers in reputed journals and has been serving as a Faculty in most of the neurology conferences. He has got an extensive experience of organizing and conducting conferences in the field of neurology and has been awarded by State Government for the contribution to social welfare.
Abstract:
Parkinson’s disease is a neurodegenerative disorder that affects approximately 1% of people over the age of 60 years. Levodopa is standard, and often initial, therapy for patients with this condition. However, with continued treatment and as the disease progresses, up to 80% of patients experience ‘wearing-off’ symptoms, dyskinesia and other motor complications. Younger age of Parkinson’s disease onset, disease severity, and high levodopa doses increase the risk of development of levodopaâ€induced dyskinesia (LID). Recent studies indicate the importance of pulsatile stimulation of striatal postsynaptic receptors in pathogenesis of LID. The nonâ€human primates with MPTPâ€induced Parkinsonism serve as a useful model to study dyskinesia. Once established, LID is difficult to treat and, therefore, efforts should be made to prevent it. The therapeutic and preventative strategies for LID include using a lower dosage of levodopa, employing dopamine agonists as initial therapy in Parkinson’s disease such as amantadine, use of atypical neuroleptics and neurosurgery. In recent studies, among 124 patients with Parkinson’s disease, 87 (70%) had received a levodopa preparation. Among these 87 patients, 28% were experiencing treatment-induced dyskinesias and 40% showed response fluctuations. The newer, non-ergoline dopamine agonists such as pramipexole and ropinirole have undergone extensive studies to evaluate their efficacy as monotherapy in early Parkinson’s disease. Amantadine is a non-competitive NMDA receptor antagonist shown to lower dyskinesia scores and improve motor complications in patients with Parkinson’s disease when given adjunctively with levodopa. These newer agonists are ideal initial symptomatic medications, primarily because they delay the onset of levodopa-induced motor fluctuations. So, it can be concluded that there is less chances of developing dyskinesia when patient is on newer anti parkinsonian drugs as compared to older agents.
- Workshop
Location: Raume / Room - 4
Session Introduction
Kjell Fuxe
Karolinska Institutet, Sweden
Title: The impact of DA heteroreceptor complexes and their receptor-receptor interactions in Parkinson’s disease and its treatment
Time : 14:30-15:30
Biography:
Kjell Fuxe is a Professor of Histology at Karolinska Institutet since 1979. He was the Member of Nobel Assembly from 1986-2005. He achieved his Honorary Doctorates at the Universities of Barcelona, Ferrara, Malaga, at Universite Claude Bernard, Lyon, at Marquis Guiseppe Scicluna International University Foundation and at the Albert Einstein International Academy Foundation. He has received a significant number of awards and published over 1500 papers in neuroscience. 1209 of them are found in Pubmed. His major achievements involve pioneering work on central monoamine neurons, the existence of volume transmission, receptor-receptor interactions in heteroreceptor complexes and in neuro-endocrinology and neuro-psychopharmacology.
Abstract:
Several types of D2R and D1R heteroreceptor complexes were discovered in the indirect and direct pathways of the striatum, respectively. Changes in the function of the DA heteroreceptor complexes may help us understand the molecular mechanisms underlying the motor complications of long-term therapy in Parkinson’s Disease (PD) with levodopa and DA receptor agonists. In the indirect pathway, the potential role of the A2AR-D2R, A2AR-D2R-mGluR5 and D2R-NMDAR heteroreceptor complexes in PD will be covered; and in the direct pathway, the D1R-D3R, A1R-D1R, D1R-NMDAR and putative A1R-D1R-D3R heteroreceptor complexes in PD will be covered. D1R and D2R heteroreceptor complexes in the brain open up a new understanding of the wearing-off of the anti-Parkinson actions of levodopa and DAR agonists and the production of levodopa induced dyskinesias. Today, it seems as if the major advantage of DA receptor agonists is that they can postpone, in early PD, the use of levodopa which gives a higher incidence of dyskinesias in PD patients vs. ropinirole and pramipexol. The motor complications can involve a reorganization of the D1R and D2R heteroreceptor complexes and a dis-balance of the D1R and D2R homomers versus non- DA receptor homomers in the direct and indirect pathways. Through understanding these mechanisms, new strategies for the treatment of motor function deficits in PD can be offered with reduced motor complications. However, the motor deficits due to degeneration of non-dopaminergic neurons will remain.The relevance of interactions of the receptor protomers in the signaling cascades and the transcriptional regulation will also be discussed including downstream target proteins.
- Young Researcher Forum
Location: Raume / Room - 4
Session Introduction
Marleen Huijben-Schoenmakers
University of Amsterdam
Title: The effects of increased therapy time on cognition and mood in frail patients with a stroke who rehabilitate on rehabilitation units of nursing homes in the Netherlands: A protocol of a comparative study
Time : 16:00-16:30
Biography:
Marleen Huijben-Schoenmakers has completed her Master of Science (Nursing) at the University of Utrecht. Furthermore, she studied Ethical Care at the Radboud University of Nijmegen and presently, she is a PhD Candidate at the Free University of Amsterdam and she is a Lecturer at the Avans University for Applied Sciences in Breda, Netherlands. Her research topics are focused on stroke rehabilitation. She has developed and implemented the exercise map on stroke units in nursing homes and by this the therapy time increased significantly by 50% to 150 minutes a day. She is now examining if the increased therapy time affects cognition in stroke patients
Abstract:
Background: Recovery after stroke is dependent on how much time can be spent on rehabilitation. Recently, we found that therapy time for older stroke patients on a rehabilitation unit of a nursing home could be increased significantly from 8.6 to at least 13 hours a week. This increase was attained by the implementation of interventions focused on strength, mobility and balance. Nurses carried out these exercises with the patients during their daily activities. The aim of the present study is to investigate if increased therapy time has a positive effect on cognition, mood (depression and anxiety) and ADL in stroke patients. Methods: A comparative single blind controlled study will be applied. Patients suffering from a stroke and staying in one of the rehabilitation units of the nursing homes are eligible for participation. Participants belong to the intervention group if they stay in two nursing homes where four interventions of the Clinical Nursing Rehabilitation Stroke Guidelines were implemented. Participants, who stay in two nursing homes where therapy is given according to the Dutch Stroke Guidelines, are included in the control group. Clinical neuropsychologists will assess patients’ cognitive functioning, level of depression (mood) and anxiety. Nurses will assess a Barthel Index score on a weekly basis (ADL). These variables are measured at baseline after 8 weeks and at the moment when participants are discharged from the nursing home. Discussion: The present study evaluates the effect of increased therapy time on cognition, mood (level of depression and anxiety) and ADL in stroke patients. When positive effects will be found this study can guide policy makers and practitioners on how to implement more therapy time on rehabilitation wards of nursing homes.
Arunasalam Balamanogaran
Gomel State Medical University, Belarus
Title: Hyperkinetic movement disorders, differential diagnosis and treatment
Time : 16:30-17:00
Biography:
Arunasalam Balamanogaran studying at Gomel state Medical University in Belarus. He was interested in medical researches. He had good research experience and knowledge with pharmacology, path physiology, neurology.
Abstract:
Parkinson’s disease, the most common hypokinetic movement disorder, has received much attention from the clinical and scientific community, but there has been a relative paucity of comprehensive reviews of hyperkinetic disorders, even though they are equally or even more disabling. Hyperkinetic movement disorders include tremors, dystonia, chorea, tics, myoclonus, stereotypies, restless legs syndrome, and various other disorders with abnormal involuntary movements. Substantial progress has been made in the understanding of the role of the basal ganglia in the pathophysiology of these hyperkinesia disorders and in motor control, muscle tone, posture, and cognitive processes. Although therapies that target pathogenesis are still lacking, effective management of hyperkinetic movement disorders demands that physicians are knowledgeable about current and novel pharmacological and surgical approaches. In addition to tetrabenazine, a monoamine-depleting drug, new formulations of botulinum toxin are being increasingly used in the treatment of these movement disorders. Finally, success with surgical approaches, particularly deep brain stimulation in patients with Parkinson’s disease who have levodopa-induced dyskinesia’s, has been extended to the treatment of many hyperkinetic movement disorders.