Tanz Neuroscience Building 
6 Queen's Park Crescent West 
Toronto, Ontario  MSS 3H2 
e-mail: crnd.info@utoronto.ca
phone:(416) 978-1871  fax: (416) 978-1878
 

About the CRND

The Centre for Research in Neurodegenerative Diseases (CRND) at the University of Toronto’s Faculty of Medicine provides international leadership in research, education and discovery related to neurodegenerative diseases. 

The CRND’s mandate is to discover, apply and disseminate knowledge that will lead to the prevention of neurodegenerative diseases, to the diagnosis and cure of individuals afflicted with these disorders, and to easing the burden of their caregivers and families. These neurodegenerative diseases include Alzheimer’s Disease, Parkinson’s Disease, Frontotemporal Dementia and related tauopathies, Amyotrophic Lateral Sclerosis (ALS or Motor Neuron Disease), Ataxia-Telangiectasia and prion diseases, such as Creutzfeldt-Jakob Disease (CJD), spongiform bovine encephalopathy (Mad Cow Disease) and scrapie.

The CRND is an interdisciplinary research institute that brings together scientific expertise in Genetics, Molecular and Cell Biology, Protein Chemistry, Transgenic Animal Modeling, Neuropathology, Neuronal Function and Neuroimmunology. 

Ongoing projects include:

Identifying new genes, mutations in which confer susceptibility to Alzheimer’s Disease, Parkinson’s Disease and other adult-onset dementias;

Understanding the age-related factors that contribute to the development of neurodegenerative disorders;

Determining the role of amyloid proteins in neurodegeneration and developing therapeutic agents to combat these biological processes;

Diagnosing and preventing prion diseases;

Deciphering the interactions of different prion proteins in regulating programmed cell death;

Investigating the role of neuronal activity on the subcellular distribution of alpha-synuclein, a Parkinson’s Disease-related protein;

Discovering how pathogenic mutations and epigenetic factors influence cellular survival and the activity of stress response pathways in diseases like Alzheimer’s and Ataxia-Telangiectasia.

Director's Report, 2004-2005

During the 2004-2005 academic year, there have been a number of exciting scientific advances.

	In Alzheimer’s Disease, we have continued to explore novel potential therapies for Alzheimer’s Disease.  Thus, in animal model studies, we have shown that a series of compounds appear to block the aggregation of the amyloid β-protein fragment into neurotoxic clumps (technically termed oligomers).  

These studies look sufficiently interesting, that we have decided to advance the best of these compounds into early clinical trials.  These compounds appear to have little toxicity, get into the brain very easily, and appear in the studies done to date, to be quite effective in animal models of Alzheimer’s Disease.  

Another therapeutic strategy that we are pursuing is to block the production of amyloid β-protein by inhibiting the enzymes which cut amyloid β-protein fragment out of the longer amyloid precursor protein.  A specific goal of this research was to find proteins which naturally regulate the activity of this enzyme. 

This would then allow us use rational computer-assisted drug design methods to design new compounds which might bind to this regulator and switch the enzyme off.  Studies using the latest cutting edge technologies at the CRND, which are nearing completion, have identified just such a regulatory protein.  

During the next year, we will use all of the high technology available to us at the CRND to fully characterize this protein, and decide how to use it to develop new therapies to block the production of amyloid β-protein.  Over the past several years, researchers at the CRND have played a key role in identifying 

several genes causing Alzheimer’s Disease.  We know, however, that these genes do not account for all of the cases of familial Alzheimer’s Disease.  During the past year, we have vigorously pursued studies on the genetics of AD using novel genomic and proteomic technologies.  These studies have now 

identified yet another gene which appears to play a key role in the processing of the amyloid precursor protein and the production of amyloid β-protein.  This new player in the causative mechanisms of Alzheimer’s Disease will allow us to have a better understanding of how the disease comes about, and by 

itself may also be a target for the development of new therapies to block its pathological action.

	In Parkinson’s Disease, the CRND has continued to profit by the experience gained from investigating Alzheimer’s Disease and has applied it to investigate the biology of Parkinson’s Disease.  Two new genes causing inherited forms of Parkinson’s Disease have been identified, and the CRND group has been 

instrumental in further characterizing them.  Of great significance, it turns out that the products of several of these genes (and particularly of a gene called DJ-1) may also be involved in Alzheimer’s Disease and other neurodegenerative disorders.  Again, in the coming year, the CRND group will play key roles 

in understanding how these molecules give rise to Parkinson’s Disease in particular, and what role they play in other neurodegenerative diseases.  

	A new development has been the integration of the CRND with the Toronto Western Hospital Research Institute (TWRI). This is a strategic alliance which brings together the two strengths of these institutions.  The strength of the CRND in fundamental research will enhance the strengths in the TWRI in applied 

and clinical research.  This is particularly noteworthy in the area of neurodegenerative disease where the strengths of the CRND have been in basic research on Alzheimer’s Disease and Parkinson’s Disease, whereas the strength of the TWRI has been in clinical research, principally on Parkinson’s Disease.  

During the coming years, this alliance will lead to dramatic increases in our ability to conduct very basic research, to under-stand how these basic research discoveries impact neurodegenerative diseases, and then implement the knowledge gained from these basic research studies at the bedside.    

Acknowledgements

The work of the CRND would not be possible without the continued generous support of the Alzheimer’s Society of Ontario and its member chapters and of many private donors. In particular, the CRND would like to acknowledge the dedicated efforts of the members of the External Advisory Committee, among them, Mark Tanz (Chair), Lionel Schipper (Vice-Chair), James Bullock, Jack and Mary Clark, Alfredo DeGasperis, A. Ephraim Diamond, John Ellis, Paul Godfrey, Peter Godsoe, Ralph Halbert, William Bernard Herman, James Redpath, Maureen Sabia, Theodore Sherman, Tony van Straubenzee, Bernie Tanz and Burton Winberg.

Funding for research has been provided by, among others, the Alzheimer’s Society of Ontario, the Canadian Institutes of Health Research, the Parkinson Foundation, the Ontario Mental Health Foundation, the Scottish Rite Charitable Foundation, the Canadian Genetic Diseases Network and the Howard Hughes Medical Institute.