Parkinsons sykdom p molekylrt niv

Kristin Aaser Lunde Stavanger universitetsbibliotek

30.10.2014

Who am I?

Kristin Aaser Lunde Born in Oslo, lived in Stavanger since 2003 2012: Master of Science in Biological Chemistry, UiS 2013: Seed grant from Stavanger Helseforskning 2013: Research assistant, NKB 2014: PhD grant from Helse Vest

What is my project?

PhD project title: Early onset dementia in

Parkinsons disease: molecular mechanisms and biomarker

discovery

Supervisors: Jodi Maple Grdem and Jan Petter Larsen

A collaboration between Stavanger

University, Stavanger University Hospital and St Johns University,

New York

Todays presentation

What is Parkinsons Disease?

Why study Parkinsons disease?

Ongoing research in Stavanger

My phd project

Parkinson's disease (PD) is a chronic and progressive movement disorder loss of dopamine-producing neurons in the midbrain (substantia nigra) reduce the brains ability to control movement Lewy body pathology

Incidence More than 1% over the age of 60 More than 4% over the age of 85

What is Parkinsons disease ?

Goedert, M. et al. (2012) 100 years of Lewy pathology Nat. Rev. Neurol. doi:10.1038/nrneurol.2012.242

Symptoms of Parkinsons disease Freezing of gait Stooped posture, a tendency to lean forward Dystonia Impaired fine motor dexterity and motor coordination Impaired gross motor coordination Poverty of movement (decreased arm swing) Akathisia Speech problems, such as softness of voice or slurred

speech caused by lack of muscle control Difficulty swallowing Sexual dysfunction Cramping Drooling Loss of sense of smell Constipation REM behavior disorder (a sleep disorder) Mood disorders Orthostatic hypotension (low blood pressure when

standing up). Sleep disturbances Bladder problems Weight loss or gain Vision and dental problems Fatigue and loss of energy. Depression Fear and anxiety Skin problems Cognitive issues, such as memory difficulties, slowed

thinking, confusion Dementia Medication side effects, such as impulsive behaviors

Primary motor symptoms: Resting tremor Bradykinesia Rigidity Postural instability

http://neurosciencefundamentals.unsw.wikispaces.net/file/view/parkinsons.PNG/448003022/720x301/parkinsons.PNG

Trinh, J. & Farrer, M. (2013) Advances in the genetics of Parkinson disease Nat. Rev. Neurol. doi:10.1038/nrneurol.2013.132

Parkinsons disease is a complex disease Complex disease = diseases that are caused by a number of genetic and environmental factors

Source: Leo Lang /Reuters

Disease heterogeneity: Symptoms of PD vary from person to person, as does the rate of progression Personalised medicine: The tailoring of medical treatment to the individual characteristics of each patient or each subgroup of patients. (http://www.ageofpersonalizedmedicine.org/)

http://www.pfizer.ie/personalized_med.cfm

Disease heterogeneity and personalised medicine

Population growth

Why is now a good time to study PD?

Why is now a good time to study PD?

Brain Research through Advancing Innovative Technologies (BRAIN) Initiative http://www.braininitiative.nih.gov/BRAIN-Brochure.pdf

The Human Genome project 1989 - 2003 -sequence and map all human genes http://www.genome.gov

Stavanger is a good place to study PD

NKB: The Norwegian Centre for Movement Disorders . Highly competent staff of neurologists, nurses, researchers, physiotherapists and psychologists specialising in PD treatment. ParkWest: NKB houses the Norwegian ParkWest study, one of the worlds longest running longitudinal studies of Parkinsons Disease (PD). As the study approaches its ninth year of follow up, NKB is in a unique position to study the long-term development of PD.

The aims of my phd

Lebouvier, Tasselli et al. 2010

Can we find biomolecules that can be utilized to predict PD progression? Can we detect PD at

the presymptomatic stage by the help of biomolecules?

Can we find drug targets to slow or halt disease progression?

Goedert, M. et al. (2012) 100 years of Lewy pathology Nat. Rev. Neurol. doi:10.1038/nrneurol.2012.242

Biomarkers

Biofluids: Cerebrospinal fluid Blood

Techniques: ELISA for proteins RT-qPCR for DNA or RNA

a distinct biochemical, genetic, or molecular characteristic or substance that is an indicator of a particular biological condition or process

http://2011.igem.org/wiki/images/thumb/3/31/DTU1_Central_dogma_with_regulators.png/370px-DTU1_Central_dogma_with_regulators.png

Enzyme-linked immunosorbent assay (ELISA)

http://medical-dictionary.thefreedictionary.com/ELISA+test

Real time quantitative PCR (RT-QPCR)

http://www.thermoscientificbio.com/applications/basic-rt-qpcr/

Drug targets Drug target = the biological target of a pharmacologically active drug compound

Trinh, J. & Farrer, M. (2013) Advances in the genetics of Parkinson disease Nat. Rev. Neurol. doi:10.1038/nrneurol.2013.132

Plants Zebrafish Worms Cell cultures Neurons Brains

Parkinsons Disease mechanisms and diagnosis/intervention

Parkinsons is a highly complex disorder need for multiple model systems

A complementary approach

Localisation assays Where in the cell can we find our proteins of interest?

Interaction studies

Yeast-two-hybrid Bimolecular fluorescence complementation

?

C. elegans as a model organism

Tiny worm 1 mm long 3 days generation time Transparent Simple nervous system: 302 neurons 8 dopaminergic neurons

1. Parkinsons disease is a complex disease caused by both genetic and environmental factors

2. We need to detect and develop biomarkers for: Presymptomatic diagnosis Prediction of disease progression

3. We need to develop drugs that can slow down or halt

disease progression.

4. We need to increase our understanding of PD at the molecular level in order to conquer these problems.

Summary

Groups:

Funding: NFR, NKB, Norges Parkinsonforbund, Helse Vest, Michal J Fox Foundation

UNIVERSITY OF WESTIMINSTER

Jodi Maple Grdem Maria Doitsidou NKB

THANK YOU

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