Current Initiatives

b) Recent Developments in AD research supported by the Fund

The work of Dr Karen Cullen on Alzheimer's disease (AD) has been supported by the Fund for a number of years. In September 2005, her findings achieved international recognition through the publication of her findings in a number of international scientific journals. Subsequently, she was invited to join a US National Institute for Health group assessing the vascular basis of dementia.

The dominant hypothesis of AD has been that it is a disease caused by build-up of the amyloid protein in lesions called plaques. Hence, amyloid has been the major focus of work on the disease.

By contrast Dr Cullen postulates that the formation of plaques and 'neurofibrillary tangles' (the skeletons of dead nerve cells) may be late events in a "cascade" of events leading to dementia. Her studies indicate each plaque is the site of a small bleed or micro-haemorrhage the size of a printed 'full stop', or smaller. While the effects of a single micro-stroke are too small to cause symptoms, Dr Cullen's work suggests their cumulative effects are devastating. The nerve cells begin to degenerate from the haemorrhages, eroding cognition bit by bit.

She hypothesises that amyloid build-up is part of this sequence where, following a micro-haemorrhage "clean-up cells" have come in to stop further bleeding, creating scar tissue (the plaque) which in turn cuts off the blood supply to nerve cells, ultimately causing death of increasing areas of brain tissue, eventual shrinkage of the brain and loss of cognition.

Dr Cullen's hypothesis gains support from the following findings; a plaque contains more than 100 components, not just amyloid. Each plaque is situated on a microvessel, one of the fine capillaries distributing blood to nerve cells. Inflammation, another common characteristic in AD-affected brains, also focuses on microvessels and contains 'clean-up cells' found at sites of injury, where they have rallied to prevent further damage. Moreover, also present in every plaque is the iron-rich substance haem, an indicator of bleeding.

While debate rages about the triggers of the disease, the evidence from Dr Cullen's work provides strong support for the tangible benefits of pursuing studies on microvascular causes of the disease. The outcomes of further research down this track could support risk-reduction strategies many of which are already in place for improving cardiovascular health, such as anti-hypertensive medication and lifestyle and diet modification. Studying the causes of the microvascular break-down could also provide a gateway into attacking the disease before degeneration begins.

Dr Cullen's current studies, supported by the Fund, and being done in collaboration with Australian and Israeli scientists, focuses on these issues.

For more information on Dr Cullen's work see Newsletter #11 or go to Presentations. Also see below under International Scientific Collaborations .

(incorportating the Institute for Biomedical Research, (IBR)

a) Molecular Biology Facility
Over a 5 year period commencing in June 2000, the Fund provided support for the establishment of a joint facility to make available state-of-the-art molecular biology techniques to the 26 research laboratories from the University's Department of Physiology and Department of Anatomy & Histology which made up the IBR.

The IBR’s leadership believes this funding enabled the Institute to raise its work to a new level of joint activity not achievable without core facilities of this kind. It also greatly advanced the adoption of modern molecular approaches within the research programs of the Institute, as well as playing a significant role in enabling the IBR to attract other grants needed to make larger equipment purchases for this facility.

b) Cytometry Facility
In light of the valuable work achieved by the IBR through the Fund's support to establish the Molecular Biology Facility, the Fund has undertaken to assist with another important new initiative, the establishment of a Cytometry Facility. The Fund will continue this support to the Bosch Institute which commenced operations in April 2006 and has, since that time, incorporated the IBR and its facilities.

Cytometry is the process by which the multitude of cell types making up the human body can be counted and classified. A high proportion of biomedical research programs depend on evaluating the numbers and/or functions of these different cell types. The equipment used by the Cytometry Facility allows this counting and classification to be done using the most advanced and accurate means available as this Facility includes an apparatus which is the first of its kind to be used in Australia.

The Fund is supporting the salary of a Cytometry Officer for this facility over a period of 3 years, from 2006 to 2008. The Officer's role is to supervise the facility and assist other scientists to use the equipment. The officer is a post-doctoral scientist who is known as the Sir Zelman Cowen Universities Fund Fellow in Cytometry.

Dr Sabita Rana, Sir Zelman Cowen Universities Fund Fellow in Cytometry

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International Scientific Collaborations

 

a) Malaria Project

In November 2004 the Fund undertook to provide support over the next 3 years to a joint project between Australian and Israeli scientists aiming to improve treatment for malaria victims.

Malaria is a disease that causes major health, economic and emotional burdens for the 40% of the world’s population who live in areas where the disease is prevalent. Travellers to those areas also are at risk. There are over 400 million cases of malaria each year and 2 million deaths.

During a malaria infection, usually the body's own immune response will eliminate the parasite, but in certain people that response also may exacerbate the symptoms of malaria, in some cases leading to death.

This project will examine a number of strategies by which anti-malarial drug treatment, which boosts the body's ability to kill the parasite, could be combined with other treatments to eliminate the harmful side-effects of the immune response. This is predicted to prevent the severe complications of malaria disease and tip the balance towards a healthy outcome. The precise biological mechanisms underlying these actions will also be studied in detail.

The project is a collaboration between the laboratories of Professor Nicholas Hunt, Professor of Pathology, at the University of Sydney and Professor Jacob Golenser, Professor of Parasitology, at the Hebrew University of Jerusalem. The complimentary skills of malaria researchers working in these two laboratories will be used to tackle this important human health issue. This will also provide an opportunity to expand the skill base of both laboratories through the exchange of skills and personnel which will be involved over the next 3 years.

In light of the growing resistance of certain strains of malaria to currently available antimalarial drugs, the need to find improved therapy for this disease has become increasingly more urgent. It is hoped that the project will lead to a practical research outcome that will influence clinical practice in treatment of this enormously important infectious disease.

Professor Nicholas Hunt, Professor of Pathology, University of Sydney

Jacob Golenser, Professor of Parasitology, HU  Jerusalem.

b) Alzheimer's Disease Project

Beginning in 1996, with its Alzheimer's Disease and Inflammation Initiative (ADI) the Fund has supported research into the vascular basis of dementias. In the years since, the scientific evidence for this idea has grown, partly from studies funded in the ADI. An international collaboration between Australian and Israeli scientists, supported by the Fund, is underway to explore the cellular and molecular basis of this idea.

Central to the project is the recent work of Dr Karen Cullen, at the University of Sydney. Her work on the neuropathology of demented brains is being investigated in conjunction with Professor Eli Keshet, at the Hebrew University of Jerusalem, Professor Nick Hunt at Sydney, and Professor Jonathan Stone, at the Australian National University.

As part of this work over the last few years, Dr Cullen has developed a 'moving picture' concept of how vessel breakdown leads to the widespread loss of nerve cells, and dementia. The team will test this concept.

This pioneering project has the potential to open totally new avenues of therapy for Alzheimer's disease and similar dementias by employing drugs, some already available, which protect the stability of the blood vessels of the brain.

For more information on Dr Cullen's work see Newsletter #11 or go to Presentations.