Merja Voutilainen team

Contact information

Merja Voutilainen
PhD, Principal Investigator
Tel. +358 2941 59456
Fax. +358 2941 59366
e-mail: merja.h.voutilainen-at-helsinki. fi

Institute of Biotechnology
P.O.Box. 56, 00014 University of Helsinki
Street address: Viikinkaari 5D, Biocenter 2

 

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Merja Voutilainen, PhD
Docent (Adjunct Professor, Pharm.)
















REREARCH INTERESTS

i) Novel treatments for neurodegenerative diseases
We are studying CDNF/MANF family of neurotrophic factors and GDNF family ligands and receptors. Currently we are mainly focused on two major diseases, Amyotrophic lateral sclerosis (ALS) and Parkinson’s disease and trying to find neurorestorative treatments that promote functional recovery from the disease.

ii) Amyotrophic lateral sclerosis (ALS)
ALS is a rapidly progressing fatal motoneuron (MN) disease characterized by progressive degeneration of MNs. There is no treatment for ALS that could halt the progression or cure the disease, thus there is a crucial medical need to find drug therapies that would slow disease progression, treat the disease and extend survival of the patients. The clinical hallmark of ALS is the combination of upper and lower MN signs and symptoms, causing muscle weakness with a wide range of disabilities. Most patients with ALS die from respiratory failure, usually within 1 to 3 years from the onset of symptoms. Our aim is to find therapies that could protect from motoneuron loss and improve the survival from the disease. We use wide array of preclinical methods.

iii) Parkinson’s disease
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the cardinal motor symptoms of tremor, rigidity, postural stability and bradykinesia. In PD dopaminergic cells die most prominently in the area of substantia nigra. Current therapies of PD do not prevent the progression of the disease and the efficacy of these treatments wanes over time. We aim to find a treatment that stops the neurodegeneration and restores the dopamine function above the level of clinical symptoms. The aim of the neurorestoration therapy is to reverse the intracellular environment towards restoration of the dopamine phenotype. In finding restoration therapy we have focused on neurotrophic factors and small molecules. We are using 6-OHDA model in mice and rats and MPTP-mouse model of Parkinson’s disease (Airavaara et al., 2013; Voutilainen et al., 2011]. We are looking at the mechanisms of neurodegeneration as well as neuroprotection and neurorestoration with a wide array of methods. We study these phenomena starting at the molecular and cellular level, and up to the neuronal networks. Furthermore, we are using electrophysiological and electrochemical methods to look at the function of nigrastriatal dopaminergic pathway, ie. the activity of the neurons in substantia nigra and the dopamine kinetics (release and reuptake) at their terminals in striatum. We have several novel mouse models, in which we can study GDNF, CDNF and MANF biology, and master a wide array of behavioral tests routinely used to study dopamine-regulated behaviors.

GROUP MEMBERS

Francesca De Lorenzo MSc, PhD student


 

 

 

 

 



Polina Stepanova MSc, PhD student

 

 

 

 

 

 



Katrina Albert MSc, PhD student

 

 

 

 

 

 



Juho-Matti Renko MSc (Pharm), PhD student

 











Sara Figuerola Santamonica MSc, PhD student











Pushpa Khanal BSc, MSc student

Thomas Tallberg BSc (Pharm), MSc

COLLABORATION
International: Prof. Michael Sendtner (University of Würzburg, Germany),  Prof. Virginia Lee (University of Pennsylvania, USA), Dr. Kelvin Luk (University of Pennsylvania, USA), Prof Xugang Xia (Thomas Jefferson University, USA), Prof Patrick Mehlen (INSERM, Centre Léon Bérard, University of Lyon, France), Prof Deniz Kirik and Åsa Petterson (University of Lund, Sweden)

National: Prof Anu Wartiovaara, Prof. Dan Lindholm, Prof. Kari Alitalo, Dr. Kira Holmström, Dr. Mikko Airavaara, Dr. Andrii Domanskyi (University of Helsinki)

FUNDING
Academy of Finland
Jane and Aatos Erkko Foundation
Center for international mobility (CIMO)
Päivi and Sakari Sohlberg Foundation
Finnish Cultural Foundation
Alfred Kordelin Foundation
Ella and Georg Ehnrooth Foundation
Finnish Parkinson Foundation

PUBLICATIONS

Voutilainen M.H., Arumäe U., Airavaara M. and Saarma M. Therapeutic Potential of Endoplasmic Reticulum Located and Secreted CDNF/MANF Family of Neurotrophic Factors in Parkinson's disease. FEBS lett 589: 3739-3748 (2015).

Nadella R., Voutilainen M.H., Saarma M., Gonzalez-Barrios J.A., Leon-Chavez B.A., Dueñas Jimenez J.M., Dueñas Jimenez S.H., Escobedo L. and Martinez-Fong D. Transient transfection of human CDNF gene reduces the 6-hydroxydopamine-induced neuroinflammation in the rat substantia nigra. J Neuroinflamm 11: 209 (2014).

Bäck S., Peränen J., Galli E., Pulkkila P., Lonka-Nevalaita L., Tamminen T., Voutilainen M.H., Raasmaja A., Saarma M., Männistö P.T. and Tuominen R.K. Gene therapy with AAV2-CDNF provides functional benefits in a rat model of Parkinson’s disease. Brain Behav 3: 75-88 (2013). Open access journal, no IF number available

Airavaara M., Harvey B.K., Voutilainen M.H., Shen H., Chou J., Lindholm P., Lindahl M., Tuominen R.K., Saarma M., Hoffer B. and Wang Y. CDNF protects the nigrostriatal dopamine system and promotes recovery after MPTP treatment in mice. Cell Transplant 21: 1213-1223 (2013).

Airavaara M.,*, Voutilainen M.H.,*, Wang Y., Hoffer B. Neurorestoration (review). Parkinsonism Relat Disord 18: S143-146 (2012). * equal contribution.

Voutilainen M.H., Bäck S., Peränen S., Lindholm P., Raasmaja A., Männistö P., Saarma M. and Tuominen R.K. Chronic infusion of CDNF prevents 6-OHDA-induced deficits in a rat model of Parkinson’s disease. Exp Neurol 228: 99-108 (2011).

Voutilainen M.H., Bäck S., Pörsti E., Toppinen L., Lindgren L., Lindholm P., Peränen J., Saarma M. and Tuominen R.K. Mesencephalic astrocyte-derived neurotrophic factor is neurorestorative in rat model of Parkinson’s disease. J Neurosci 29: 9651-9659 (2009).

Lindholm P., Voutilainen M.H., Laurén J., Peränen J., Leppänen V-M., Andressoo J-O., Lindahl M., Janhunen S., Kalkkinen N., Timmusk T., Tuominen R.K. and Saarma M. Novel neurotrophic factor CDNF protects and rescues midbrain dopaminergic neurons in vivo. Nature 448: 73-77 (2007).

Abin-Carriquiry A., Voutilainen M.H., Barik J., Cassels B.K., Bermudez I., Dajas F. and Wonnacott S. C3-halogenation of cytisine generates potent and efficacious nicotinic receptor agonists. Eur J Pharmacol 536: 1-11 (2006).