The University of Sydney
spcr
spcr
spcr
spcr
spcr
Large text
spcr
Default text
spcr

Archive of Past Initiatives

ALZHEIMER’S DISEASE RESEARCH

 

a) Alzheimer's Disease and Inflamation Initiative

In May 1996 the Fund established the Alzheimer’s Disease and Inflammation Initiative (ADI) to examine the idea that anti-inflammatory drugs may provide protection against the onset and progress of the dementia that characterises Alzheimer's disease (AD).

Inspiration for the Initiative came from Australian and overseas reports that the anti-inflammatory drugs taken by significant numbers of patients for conditions like arthritis appeared to protect them against the debilitating dementia characteristic of AD. The protection was substantial, the incidence of AD being as little as 25% of that found in the general community.

A team of eminent scientists was brought together to examine the significance of these reports in the Australian context. The team included Professor Tony Broe, Dr Bill Brooks and Dr. Jillian Kril from the Centre for Education and Research on Ageing at Concord Hospital and Dr Glenda Halliday from the Prince of Wales Medical Research Institute.

A maverick move in 1996, this line of research has now been taken up by many researchers worldwide and may soon play a major role in unravelling the cause of this frightening disease.

Since that time the Fund has supported a number of other research projects aimed at finding the cause and a potential cure, for the dementia of Alzheimer’s disease (AD).

ADI Report 2001

Scientists
Four of the scientists involved in the ADI (L-R): Drs Karen Cullen, Jillian Kril, Claire Shepherd and Bill Brooks

b) The work of Dr Karen Cullen and The Microvascular Basis of Alzheimer's Disease

The work of Dr Karen Cullen on Alzheimer's disease (AD) was supported by the Fund from 1998 – 1999 as one of a number of projects which were part of the ADI. Her findings enabled her to attract funding from Pfizer Inc to continue her investigations into the origins of AD. In September 2005, her work achieved wide 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.

For a long time, 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 postulated 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.

Hence, to explore these ideas further, the Fund undertook to support a new project commencing in 2005 and entitled, The Microvascular Basis of Alzheimer's Disease. The project was a collaboration between the laboratories of Dr Cullen & Prof Nick Hunt at the University of Sydney, Prof Jonathan Stone, then at the ANU, Canberra and Prof Eli Keshet, at the Hebrew University of Jerusalem.

In her final report on the project, Dr Cullen wrote, “The work has had significant success and receives ongoing recognition, evidenced by reviews of the work in Nature Clinical Practice Neurology and in invitations to speak at international meetings on vascular dementia. I have been pleased that the work continues to confirm the vascular origin in AD and has effected a paradigm shift in research into the causes and potential therapy for AD. Because of the resistance the ideas in the early years, this work could not have been easily funded by large government agencies and therefore support from private funds has been invaluable.”

For more information on Dr Cullen's work see NEWSLETTER 11 or PRESENTATIONS

FUNDING INFRASTRUCTURE PROJECTS THROUGH THE BOSCH INSTITUTE UNIVERSITY OF SYDNEY - PREVIOUSLY KNOWN AS 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 Facility 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 undertook to assist with another important new initiative, the establishment of a Cytometry Facility.



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.

INTERNATIONAL SCIENTIFIC COLLABORATIONS

 

a) Malaria Project

In November 2004 the Fund undertook to provide support over 3 years to a joint project between Australian and Israeli scientists aiming to improve treatment for malaria victims there being over 400 million cases of malaria each year, world-wide.


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 examined 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. 
The project was a collaboration between the laboratories of Prof Nicholas Hunt, University of Sydney and Prof Jacob Golenser, Hebrew University of Jerusalem. The project produced significant findings which laid the ground-work for a second SZCUF-supported collaborative project commenced in 2009 which examined the efficacy of various herbal and pharmaceutical preparations on their own; in various combinations; and in a variety of modes of administration to aid in the quest for a better therapy for malaria sufferers.
Professor Nicholas Hunt, Professor of Pathology, University of Sydney
Jacob Golenser, Professor of Parasitology, HU Jerusalem

SOME VERY EARLY INITIATIVES

 

a) Cultured Skin

Extensive skin loss, such as that caused by burns, results in serious complications and may lead to death if not prevented by early wound closure. In this project, Dr Mark Eisenberg of Sydney, working jointly with Dr Hanna Ben Bassat of Hadassah University Hospital in Jerusalem and supported by a grant from the Fund, worked to develop cultured skin for grafting purposes. Small pieces of skin from an unrelated donor were placed in culture dishes to grow into large sheets which can be transplanted to the patient to cover a wound. In experiments with skin taken from the actual burns victim, Dr Ben Bassat was able to achieve similar outcomes. Both methods have resulted in successful transplantations and ultimately to the setting-up of "skin banks" where skin produced by these methods is able to be stored for later use.


b) Use of Interferon in the Treatment of Leukaemia

With the assistance of the Sir Zelman Cowen Universities Fund, Dr Tony Basten working at the Clinical Immunology Research Centre at the University of Sydney studied the use of Interferon on patients with a particular type of leukaemia which did not respond well to any type of therapy. It had a dramatic effect on these leukaemia patients and soon came to be regarded as the mainstay of treatment for this type of leukaemia.