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Repurposing Cancer and depression drugs for use in dementia - Dr Lucy Stirland comments

Thursday 25 May 2017

Dr Lucy Stirland is a Clinical Research Fellow in the Centre for Dementia Prevention at the University of Edinburgh.  She is also an honorary specialty registrar in Old Age Psychiatry in Edinburgh.  Currently undertaking a PhD, she is looking at the links between physical and mental health in later life using big data.  Her aims are to find out whether having numerous physical conditions or taking several medications at once are associated with mental health problems including dementia.

Find out more about Dr Stirland here: http://edin.ac/2qdj7bE

Dr Stirland provided her commentary on recent headlines claiming it may be possible to repurpose two existing drugs - a Cancer drug and a drug for depression – for use against dementia, versus the findings of the study to which they refer.

1. Were the headlines right or were they misleading in some way?

This research paper attracted attention as it reports a promising step towards finding a new treatment for dementia.  However, this was laboratory based experimental work in mice and the treatments in question are very far from being ready for use in people. The news reports were generally balanced and included quotes from scientists both optimistic and more cautious.  Some headlines such as “Experts ‘excited’ at HUGE breakthrough in hunt for cure” were perhaps exaggerated.  There are no suggestions that these drugs would cure dementia, only that they could protect against brain cell death.  Speculation that the drugs may be ready for public use in as little as two years is also very optimistic, given the length of time taken to set up a clinical trial. Most of the reports stressed the fact that these findings in mice do not automatically translate to the same effects in humans, therefore tempering any disproportionate enthusiasm.

2. How important is this story/study for furthering dementia research? Should we be excited?

This study was very thorough. The researchers used a library of 1,040 existing substances and tested these first in worms, then 20 promising ones in cell models, before choosing the two drugs they tested in mice: trazodone and dibenzoylmethane.

Trazodone is already used as an anti-depressant. As some of the news articles mention, it is sometimes given to people with dementia to alleviate symptoms including sleep disturbance and agitation.  However, it causes sedation so is usually used in small doses and some people find it too sedating to be helpful.  Dibenzoylmethane has been used in studies for some cancers but is not currently used in clinical practice.  Neither of the drugs studied have previously been found to protect brain cells.

The mice in this study had already a developed brain disease, which behaves in a similar way to frontotemporal dementia. The behaviour and memory of most of the mice improved with the drugs and there was evidence that their brain cells were protected from death. Most of the mice given the drugs survived longer than those without them. This is potentially exciting news because one of the drugs in question is already prescribed in humans and is therefore known to be safe in its current usage.  If the protective effects are found to occur in humans too, then the drug could be used in practice much more quickly than a completely new compound which would have to go through years of safety testing.

3. What might be the impact of this story/study in the scientific community?

The study was based on prior understanding of a process that protects brain cells. It used efficient methods to screen over 1,000 existing substances for effectiveness, before doing more detailed tests on just two compounds in mice. These methods, allowing existing medications to be “repurposed”, are being used in studies of other diseases and will be useful in finding new treatments more quickly and cheaply. Now that these drugs have been identified as potentially useful, there will likely be more studies involving them and eventually testing them on humans.

4. What are the next steps?

As with all new findings, these need to be replicated in further research. This study has made an important step by finding a benefit from these drugs in mice. The study’s authors have called for clinical trials of trazodone and dibenzoylmethane to test whether their protective effect will also be seen in humans. It is likely to take several years before we know whether the drugs will be helpful treatments for dementia.  There are several different disease processes which contribute to developing dementia and this study only focussed on one; therefore parallel work needs to continue looking at other pathways.

5. Should I/my relative with dementia seek a prescription of trazodone if it is already available?

This study has found some benefit from using trazodone in mice with brain diseases.  At this early stage, we do not know if this will be beneficial or safe for treating dementia in people. As with all drugs, it has side effects and its interactions with other prescriptions must be considered. It should therefore not be used as a treatment for dementia until results of studies of its use in humans are available. It would also need to be licensed for its new use by the appropriate regulatory bodies.

Biography

Original paper: Halliday M, Radford H, Zents KA, Molloy C, Moreno JA, Verity NC, Smith E, Ortori CA, Barrett DA, Bushell M, Mallucci GR. Repurposed drugs targeting eIF2α-P-mediated translational repression prevent neurodegeneration in mice. Brain. 2017 Apr 19.

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