Mart Saarma lab

Contact information

Mart Saarma
Professor
Tel. +358 50 5002726
Fax. +358 2941 59366
e-mail: mart.saarma-at-helsinki dot fi

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

 

 

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Novel treatments for neurodegenerative diseases

The detailed molecular focuses are explained in CDNF/MANF family of neurotrophic factors and GDNF family ligands and receptors. Currently we are mainly focused on two major diseases Parkinson’s disease and ischemic brain and trying to find neurorestorative treatments that promote functional recovery from the disease.

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 [1-3]. 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.

Stroke
Cerebral ischemia severely compromises energy supply to brain either focally by arterial blockage (stroke) or globally (cardiac arrest). Within seconds of initiation of global brain ischemia, consciousness is lost and, if it lasts for 5 minutes or more, severe brain damage is induced. Stroke is the third leading cause of death and disability of humans and the number one cause for reduction in quality of life in elderly people. We are focused on prevention of damage and promotion of recovery. We use the transient distal middle cerebral ligation model for stroke [4, 5] where the infracted are is located in the cerebral cortex, and models the most common stroke type in humans. The model enables us to find novel treatments for both neuroprotection and promotion of functional recovery.

1. Domanskyi A, Saarma M, Airavaara, M (2015) rospects of Neurotrophic Factors for Parkinson's Disease: Comparison of Protein and Gene Therapy. Hum Gene Ther, in press.

2. Airavaara, M., B.K. Harvey, M.H. Voutilainen, H. Shen, J. Chou, P. Lindholm, M. Lindahl, R.K. Tuominen, M. Saarma, Y. Wang, and B. Hoffer (2012) CDNF protects the nigrostriatal dopamine system and promotes recovery after MPTP treatment in mice. Cell Transplant, 21:1213-23

3. Lindholm, P., M.H. Voutilainen, J. Lauren, J. Peranen, V.M. Leppanen, J.O. Andressoo, M. Lindahl, S. Janhunen, N. Kalkkinen, T. Timmusk, R.K. Tuominen, and M. Saarma (2007) Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo. Nature,  448: 73-7.

4. Voutilainen, M.H., S. Back, E. Porsti, L. Toppinen, L. Lindgren, P. Lindholm, J. Peranen, M. Saarma, and R.K. Tuominen (2009) Mesencephalic astrocyte-derived neurotrophic factor is neurorestorative in rat model of Parkinson's disease. J Neurosci, 29(30): p. 9651-9.

5. Airavaara, M., M.J. Chiocco, D.B. Howard, K.L. Zuchowski, J. Peranen, C. Liu, S. Fang, B.J. Hoffer, Y. Wang, and B.K. Harvey (2010) Widespread cortical expression of MANF by AAV serotype 7: Localization and protection against ischemic brain injury. Exp Neurol, 225:104-13.

6. Airavaara, M., H. Shen, C.C. Kuo, J. Peranen, M. Saarma, B. Hoffer, and Y. Wang (2009) Mesencephalic astrocyte-derived neurotrophic factor reduces ischemic brain injury and promotes behavioral recovery in rats. J Comp Neurol, 515:116-24.