Two scientists at Macquarie University have discovered a new treatment that can reverse the effects of memory loss associated with Alzheimer’s disease in a study of mice, the leading cause of death for women and the second leading cause of death of all Australians.
The “ground-breaking” treatment developed by the scientists – who happen to be brothers – reversed the effects of memory loss related to Alzheimer’s disease in a study of mice with advanced dementia.
By activating a “naturally protective enzyme in the brain called p38gamma, the scientists were able to eliminate the toxic effects leading to memory loss”. Not only has this discovery shown promise for Alzheimer’s disease, the researchers believe it could hold potential for treating other dementia-related diseases, such as fronto-temporal dementia, which typically affects much younger people in their 40s and 50s.
Lars and Arne Ittner from Macquarie’s Dementia Research Centre have dedicated more than a decade of their lives to studying dementia treatments. The breakthrough for the treatment apparently came when Arne discovered that gene therapy was able to replace a protective enzyme in the brain with “outstanding impacts on memory in advanced dementia”.
Arne said increases in Alzheimer’s disease in Australia are attributable to our ageing population and highlighted the high mortality rate.
“Numbers-wise, basic science has managed to reduce the mortality of all major diseases – cancer, diabetes, blood pressure and so forth – but we are still seeing increases in Alzheimer’s disease, and so getting into the space and doing something about it is of utmost importance.”
In completely reversing memory loss in mice, the brothers achieved more than they set out to do in their hypothesis. Originally, their goal was merely to halt the deterioration of memory.
“We were completely surprised,” Lars Ittner said.
“They actually recovered their memory function and their ability to learn returned. So, two months after we treated the mice at very old ages, these mice suddenly behaved like their normal siblings. We were really stoked. There is no comparable therapy out there and no other gene therapy either.”
Before testing began, the Ittners’ aim was to rebuild the lost enzymatic memory activity of the mice and make it more efficient. By researching memory impairments in mice at advanced stages of dementia, “they found that activating p38gamma can modify a protein such that it prevents the development of Alzheimer’s disease symptoms”.
As Lars Ittner explained: “The naturally protective enzymatic activity in the brain is unfortunately lost the further you progress down the Alzheimer’s disease track – so the more memory you lose, the more you also lose this natural protective effect.”
The “world-first”’ findings will be published in the September edition of the journal Acta Neuropathologica, and the researchers believe their gene therapy approach to treating Alzheimer’s disease “has the potential to put Australia on the map”.
Arne Ittner said that, traditionally, researchers have had difficulty modelling dementia experiments as, by the time the person with dementia or their family notices any peculiarities, they are “already quite far down the memory defect lane”. He believes gene therapy will be “especially significant” in alleviating this difficulty.
“By its nature, the neurodegeneration is incredibly slow which is notoriously hard to study and hard to model,” he said.
“The brain is a black box and some days we get lucky and get glimpses of how it functions, and we learn we can interfere with the mechanism in this black box. Now we have detailed understanding of the mechanisms involved down to the amino acids, which is just quite unprecedented.”
Professor Dan Johnson, pro vice-chancellor of Research Innovation at Macquarie University, said they were “hopeful of realising immediate local benefits”.
“If all goes well, we may find ourselves with a clinical trial done at Macquarie Hospital with this therapy,” he said.
“Macquarie is investing in the uniqueness of the science and the supporting intellectual property position.”
“A lot of the focus right now is on the fundamental science breakthrough and this is clearly a significant achievement. The next phase takes on an additional level of complexity, cost and time to deliver.”
The university is currently deciding the best way to develop the therapy before commencing a clinical trial. If the therapy’s success story continues, the researchers hope the gene therapy can be commercialised within five to ten years.
As gene therapy can be prohibitively expensive, the duo is seeking investors and partners to progress the treatment. However, according to Johnson some of the world’s biggest pharmaceutical companies have already shown interest in the therapy’s potential.Do you have an idea for a story?
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