Wednesday, 10 February 2016

Research into repurposing drugs for leukaemia

Leukaemia & Lymphoma NI have finally joined the rest of the world in blogging - perhaps a bit later than everyone else but we thought this would be a good forum to let the public know a bit more about the research we support here in Belfast. We plan to update the blog each month with some more information on research projects funded by the charity, currently we fund 2 PhD students, 2 Post Doctoral Scientists and a Clinical Research Fellow, all of whom you will hear from along the way. 

The first project we are going to look at is the brainchild of Dr Kyle Matchett – Kyle is one of our Post Doctoral Scientists.

Between 2009 and 2013 699 people were diagnosed with a type of blood cancer in Northern Ireland, Leukaemia accounted for almost 30% of these cases and is of particular interest to Kyle due to the poor survival rates.  A general statistic for the 5 year survival rate of Leukaemia is 48%, this figure will vary depending on the type of illness but in comparison to other blood cancers it is poor.

Kyle’s area of interest looks at 2 different types of leukaemia – AML and MLL

AML – Acute myeloid leukaemia. This type of blood cancer is most common in patients over the age of 67, the body creates abnormal white blood cells which don’t work effectively making the patient more prone to illness and infection.

MLL – Mixed lineage leukaemia. This type of blood cancer is most common in young children, it occurs when a piece of one chromosome has broken off and reattached to another causing very high levels of white blood cells. When the blood is crowded with white blood cells there isn’t space for red blood cells to deliver oxygen to the body adequately.

These types of Leukaemia have particularly poor survival rates because they occur in high risk patients. 

Often the drugs available are highly toxic and have other ill effects on the body so new treatments for these vulnerable are needed urgently.

Kyle’s project focuses on repurposing existing drugs which are already available on the market to treat other conditions. Using drugs which are already available has many advantages; they are easily accessible, cheaper and already approved by the government.

This avoids the huge implications in creating a new drug to treat patients; it can take up to 20 years with the average cost thought to be around $2.5 billion USD.

Research into repurposing drugs in other medical fields has shown to be successful in the past, a few examples you may be familiar with;

Drug

Original purpose

New purpose

Asprin

Inflamation/pain

Antiplatlet

Bromocriptine

Parkinsons disease

Diabetes mellitus

Methotrexate

Cancer

Psoriasis, rheumatoid arthrtis

 

Bromocriptine, traditionally a treatment for Parkinsons disease is of particular interest here as a team of researchers at CCRCB found that could be repurposed as a potential therapy for myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). Their findings have been published by Oncotarget and you can read more by clicking here.  

So how does the project work?

Cell models of each type of leukaemia are developed in the lab to test the drugs on a robot like the one below is loaded with a library of 760 FDA approved drugs, it administers 3 different concentrations of each drug to both cell models. This is done over a 24 hour period and a 48 hour period.

This screening of the drugs will produce 9,120 results in the form of data points, these points are then displayed on a chart like to one below to show how effective they have been in positively changing the leukaemia cells. All the blue dots inside the green the circle have had little to no effect on the leukaemia cells, those outside the red circle have shown positive results. In this screening a total of 38 drugs had positive results.

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Now to looks at the 38 drugs;

12 of these drugs are already established treatments for blood cancer; this confirms that the results of the screening are reliable. A further 13 of the drugs are currently being used in the treatment of solid cancer tumours.

The remaining 13 drugs are novel to the treatment of any type of cancer – these are the most interesting results which are then investigated further.

Living leukaemias form little cell clusters know as colony assays, an effective drug will break down these little clusters without causing damage to other cells.

Looking at the chart below you can see that some drugs such as MET are very successful in breaking down the leukaemia clusters but it also breaks down the normal blood cells. The most desirable results are from MB, the AML and MML clusters have been broken down but the normal blood cells at the bottom remain almost the same.

picture2.jpg?nc=1455111890

MB is medication used to treat parasitic worm infections, and is well tolerated by humans.There are current studies to suggest that it may be a promising drug in the treating cancer of the adrenal gland, lung cancer and brain tumours. Clinical trials of MB in brain tumours are currently ongoing at Johns Hopkins University and in New York.

There are no studies into the effects of MB on blood cancers making this find quite exciting. Kyle will be speaking at a number of national and international meetings this year to present his findings.

In the meantime he will continue to study MB seeking to understand how it works in Leukaemia cells, how it affects how cells grow, the genes they express and important biological processes.

Any questions on this project or anything else please don’t hesitate to get in touch.