Science Corner: Liquid biopsies for blood cancers, and treating Alzheimer’s and heart attacks
With the wealth of research and empirical information out there, it can be difficult to know where to start looking for high-quality evidence. Even if you manage to find a study you’re interested in, chances are it will be difficult and time-consuming to interpret – not to mention behind a paywall. The Doctus Project Science Corner presents new and important health and medical research in an engaging, easily-digested format, bringing the academic and real worlds closer together. We hope you enjoy.
Liquid biopsies: a more precise and less invasive way of managing blood cancers
The traditional disease monitoring strategies in blood cancers, such as chronic lymphocytic leukaemia (CLL) and myelodysplastic syndromes (MDS), involve radiological imaging and painful lymph node or bone marrow biopsies, which have numerous limitations.
A series of correspondence in Blood and Nature Communications by the Dawson laboratory at the Peter MacCallum Cancer Centre reveals a world-first ‘liquid biopsy’ blood test that can potentially serve as a minimally invasive monitoring strategy for assessing treatment response and disease progress in blood cancers.
The blood test aims to detect circulating cell-free tumour DNA (ctDNA) in different sites of the body. Tumours that have spread throughout the body are known to become different from one another, but even individual cells within a single tumour display differential gene expression. Thus, in contrast to the traditional tissue biopsy which only samples tumour cells from a single site, the new liquid biopsy has the advantage of providing a more comprehensive insight into the make-up of the tumour.
Moreover, the less invasive blood test can be repeated over time to track patients’ response to a new cancer drug and identify resistance to or failure of the therapy early. As highlighted in the paper, in the several MDS patients who progressed to acute myeloid leukaemia after initial response to first line treatment, their ctDNA analysis mirrored the changes in the malignant subclones. By reflecting the genomic changes in tumour cells that arise during therapy, the blood test can be used to pre-empt disease progression.
This use of a liquid biopsy not only relieves the burden of traditional disease monitoring methods in patients, but also allows more targeted therapies that could prove to be a big step forward in precision medicine.
Scanning ultrasound to better treat Alzheimer’s disease
The fluid surrounding our brain, known as cerebrospinal fluid, serves to protect us from circulating pathogens while allowing sufficient nutrients to diffuse into and out of our brain. However, at times this proves problematic for larger molecules, particularly drugs, that require access to the brain.
There has been ongoing research into development of antibodies against the two major proteins implicated in Alzheimer’s disease: extracellular amyloid-beta and tangles of tau deposited inside neurons. However, it has been estimated that only around 0.1% of the antibody injected peripherally actually enters the brain.
The Götz group from Queensland Brain Institute offers a resolution to this problem by using repeated focused ultrasound in a scanning mode (scanning ultrasound or SUS) to temporarily open up the blood brain barrier. Their initial findings published in Science in 2015 showed that SUS alone reduced the levels of amyloid-beta plaque in Alzheimer’s disease mice, and improved their performance in cognition and memory tasks.
More recently, their findings revealed that this scanning ultrasound technique, when combined with passive immunisation of an anti-tau antibody, enhances its delivery across the blood brain barrier and uptake into the neurons. This overcomes the additional challenge of accessing tau, as the drug has to cross the neuronal cell membrane, unlike the amyloid-beta outside of the cell.
While this is currently still under preclinical development, the scanning ultrasound appears to be an exciting strategy that can be used with many future therapeutic antibodies in Alzheimer’s disease and other neurodegenerative conditions.
Generation of 3D-printed heart muscle ‘patch’ to improve recovery from heart attack
Heart attacks (or, more properly, myocardial infarctions) are the result of a loss of blood supply and therefore oxygen to the heart muscle, leading to permanent cell death and subsequent scar tissue formation. The damaged tissue no longer functions properly, which may eventually lead to heart failure.
A number of studies have looked at cellular therapy for myocardial repair, which involves the injection of immature cardiac cells into the injured heart muscle. However, this has proven exceptionally challenging, with low engraftment rates and poor electromechanical coupling (coordination between electrical signalling and contraction) between the cardiac cells, hampering outcomes. It turns out that this may be due to the lack of appropriate structural support that normally allows synchronised contraction of cardiac cells.
A recent study published in Circulation Research describes the use of a novel technique that combines the principles of 3D printing and photochemistry to generate a myocardial extracellular matrix (ECM) scaffold – a web of supportive tissue to help the heart muscle pump effectively.
The sizes and features of the ECM components were first determined in adult mouse heart tissue and generated as a 3D template. With a special laser, researchers scanned the template and directly mapped the positions of crosslinks between the proteins onto a biological polymer with unprecedented resolution, thereby producing a native-like ECM scaffold. A human cardiac muscle patch was then generated by seeding cardiac and other supporting cells from human stem cells onto the scaffold.
The findings show that the cardiac cells beat synchronously within one day of engraftment, and, when placed onto the site of tissue damage in the mouse model, the patch led to improvement of cardiac function.
While this technique is now being tested in pig hearts, which more closely mirror the human heart, we remain hopeful in the exciting impact such new technology brings to the development of novel non-pharmacological therapies for major diseases such as cardiovascular disease and particularly heart attack, which kills an average of 25 Australians every single day.
The views and opinions expressed in this article are those of the author and do not necessarily represent those of the Doctus Project.