Anaemia one more mystery of the blood
Researchers hope that unlocking some mysteries of blood will put them on the path to better treatments for anaemia, writes Amanda Saunders
BLOOD has fascinated people for centuries and images of bloodshed continue to permeate all facets of culture, from popular art and literature to religion and even psychoanalysis. Throughout history, ancient rituals and religious ceremonies have celebrated blood as the liquid of life and used it as an important symbol of sacrificial rites.
But blood holds a place of comparable mystery in a scientific setting and researchers continue to try and uncover more of its properties.
One of the most common blood disorders is anaemia, and researchers hope that new findings will lead to better and more targeted treatments for the condition.
People with anaemia either have an insufficient red blood cell supply or a low level of the blood protein haemoglobin, which is necessary to move oxygen through the body.
Unlocking the path to new anaemia treatments is a key part of biochemist Peter Klinken’s research. Klinken, head of the Western Australian Institute of Medical Research (WAIMR), hopes that his efforts to decipher the intricacies of red blood cell production will translate into treatments that clinicians can give to their patients.
Klinken was inspired to explore the power of red blood cells during his three-year stint doing post-doctoral research at the National Institutes of Health (NIH) in Washington.
Under the lights of his supervisor’s lab, his imagination was set on fire as he watched his superior work on immature red blood cells and cancer-causing genes that had only just been discovered. The idea that one faulty gene could destroy someone’s health amazed Klinken.
‘‘ I was looking at all this and saying, oh boy, how does a blood stem cell make decisions so it turns into a red blood cell rather than a white blood cell,’’ he says.
Klinken compares decoding the answers to such questions with the task of the early explorers. ‘‘ Let’s go back 400 or 500 years to the explorers, who were supported by wealthy noblemen to discover wonderful treasures,’’ he says. ‘‘ I think we are doing much the same thing now. Society is saying to us, ‘ go out and seek new worlds’.’’
Breaking new ground in anaemia research can be difficult because the causes of the disease are varied, ranging from iron or vitamin deficiency, blood loss, chronic illness, a genetic or acquired defect and the use of some medications.
Wollongong Hospital haematologist Peter Presgrave says that while anaemia caused by iron or vitamin deficiency can be treated by taking supplements, other more serious forms of the disease can be hard to treat.
‘‘ One of the problems with diseases of the red cells leading to anaemia is that there is little that can be done unless there is a simple cause such as a vitamin deficiency,’’ Presgrave explains. ‘‘ The only other solutions are to give regular blood transfusions, at a time when there is a deal of strain on the blood supply, or treatment with erythropoietin (EPO).’’
EPO treatment is used on anaemia patients because it stimulates production of their missing blood cells. Although it held early promise, EPO is not suitable for all types of anaemia and its success rate varies, says Klinken.
Presgrave says EPO’s capacity to treat patients who have developed anaemia due to bone marrow failure is limited. ‘‘ In a condition called myelodysplasia, a form of bone marrow failure, EPO works in only 20-50 per cent of patients and has to be used in very high doses on a continuous basis,’’ he explains.
EPO also has cost problems and patients only qualify for government subsidies if their anaemia is the result of renal (kidney) failure, he says. ‘‘ If you take the ‘ average’ renal failure patient, they may need about $8000 worth of EPO per year — potentially for the rest of their life,’’ says Presgrave. ‘‘ In patients with marrow diseases, not eligible for subsidies, the doses are often considerably higher — possibly three times this, if not more.’’
David Joske, head of haematology at Sir Charles Gardiner Hospital in Perth, says EPO works on the vast majority of patients who have anaemia associated with renal failure. ‘‘ However, EPO, when it is used therapeutically, is associated with an increased risk of blood clots in some patient groups, such as those on dialysis,’’ he explains.
One of Klinken’s latest significant discoveries is set against the backdrop of imperfect treatments such as EPO, and promises the possibility of alternative treatments.
Basing its work on mice, his WAIMR team discovered a link between EPO and the thyroid hormone, which was reported in the March edition of the American haematology journal Blood (2008;111(6):3245-3248).
The research shows that the thyroid hormone, already known to affect metabolism, also contributes to red blood cell formation. However, the exact effect of thyroid on blood production has not yet been established.
‘‘ We knew there was a link between the metabolism and thyroid hormone levels and so we suddenly thought: for your metabolism to work you really need oxygen, and what carries oxygen?’’ says Klinken. ‘‘ Red blood cells do.’’
Joske says such understanding could ultimately lead to a cure for anaemia.
‘‘ If the different pathways that lead to anaemia can be identified, then they can be blocked,’’ he says. ‘‘ So we can then not only treat anaemia — we can prevent it.’’
Joske believes the research may also lead to new treatments for anaemia patients with hypothyroidism, or underfunctioning thyroid glands.
Klinken’s finding occurred by chance and coincidentally came shortly after Blood reported another of his team’s important discoveries. They unearthed a cancer-causing gene and exposed its role in regulating red blood cell production.
A study on the gene, known as Hls5, appeared in the journal in February (2008;111(4):1946-50) and offers hope of new research avenues that potentially could lead to new treatments for conditions such as anaemia, leukaemia and cancer.
Klinken was surprised to find that Hls5 controls how genes are switched on and off, and stunts the growth of developing red blood cells. He believes there are considerable prospects of altering the gene, as even minor changes in Hls5 were shown to have a large impact. ‘‘ By knowing what the function of this Hls5 gene we discovered is, we have a better understanding of its role in cancer,’’ says Klinken.
Joske thinks the research will lead to more targeted treatments for leukaemia and anaemia. ‘‘ The key message of this research is that we can get as clever about a common problem like anaemia as we have about rarer problems like leukaemia, and that promises much more specific and effective treatments in the years to come,’’ he says.
Joske also points out that more targeted treatments may mean fewer or no side effects. ‘‘ For leukaemias, what we are increasingly going to be able to do is identify the abnormal genes or molecules and target a treatment that just works against them,’’ explains Joske. ‘‘ That treatment then won’t affect normal cells.’’
However, Presgrave is not so sure that Klinken’s research will lead directly to new treatments, and says its role will relate more to increasing the understanding of processes that lead to red cell diseases and blood cancers.
‘‘ My understanding is that this research may be of benefit in blood and marrow diseases patients, who do not currently get EPO unless they pay for it, but who require regular blood transfusions,’’ he says.
Jill Finlayson, the head of haematology at PathWest in Perth, thinks the findings are important in building knowledge of the fundamental processes involved in cell development.
‘‘ This knowledge lays the foundation for understanding the interactions at a cellular level required for normal development, and may provide a key to unravelling the processes which are affected in malignancies,’’ she explains. ‘‘ This type of understanding may well lead to targeted therapies in the future.’’
Klinken will continue to attempt to fulfil his self-ascribed role as a modern day explorer. ‘‘ Society is investing in us to go forth and do good things,’’ he says. ‘‘ So we have a responsibility to come up with wonderful new discoveries.’’
Research: David Joske performs a bone marrow biopsy. Peter Klinken looks on