Download Anaemia in the womb affects heart health as an adult

HRC
news
Issue No. 80 December 2013
Anaemia in the womb affects
heart health as an adult
By Suzy Botica
Fetal
Anaemia
Study
Adults who developed a low
haemoglobin level (anaemia)
in their mothers’ wombs may
be at greater risk of heart
problems, according to a
ground-breaking study led by
paediatrician and HRC
Clinical Research Training
Fellow Dr Alexandra
Wallace.
The HRC-funded study measured
the heart function, coronary blood
flow and cardiovascular risk factors
of adult survivors of severe rhesus
haemolytic disease in New Zealand.
Rhesus disease occurs when
antibodies in a pregnant woman’s
blood destroy her baby’s red blood
cells leading to the baby developing
anaemia.
Just over half of the study’s 187
participants received an intrauterine
blood transfusion to treat their
rhesus disease-induced anaemia
at National Women’s Hospital in
Auckland between 1963 and 1992.
For comparison, the rest of the
study participants were made up
of their siblings who did not have
rhesus disease. The participants’
ages ranged from 18 to 47, with an
average age of 37.
The study is the first to look at the
effects of anaemia in the womb and
treatment with intrauterine blood
transfusion on adult heart health.
“The number of heart cells you
have when you’re born is essentially
the number you have for life. Fetal
anaemia exposes the developing
heart to physiological stress, which
may alter the replication and
differentiation of these cells before
birth,” says Dr Wallace.
The results from this study provide
the first evidence that babies who
have anaemia in the womb may have
permanently altered heart structure
and function – changes that could
potentially have lifelong health
consequences.
“Using cardiac MRI, we found that
the participants who had anaemia in
utero had smaller and thicker walled
left ventricles than their unaffected
siblings,” says Dr Wallace. “They
also had lower levels of high-density
lipoprotein (or HDL, the so-called
‘good cholesterol’) and increased
sympathetic control of heart rate
variability, both of which suggest
increased cardiovascular risk. In
addition, analysis of coronary blood
Dr Alexandra Wallace with her sons Lachie (4),
on the left, and Sam (3)
flow at rest and with stress indicates
that exposure to anaemia before birth
may also impair coronary blood vessel
function.”
Despite these differences, Dr Wallace
says all findings for those exposed
to anaemia before birth were within
normal limits, so the absolute
increase in cardiovascular risk for
these individuals is likely to be very
small at their current age. “Further
review in 10 to 20 years’ time will
help establish if they have earlier
onset or more severe cardiovascular
disease in later life.”
(Continued on page 3)
INSIDE
Door opens to new
fertility treatments
Otago researchers’ discovery offers
hope for infertile couples. Find out
more on page 16.
HRC News December 2013
IN THIS ISSUE
Upcoming closing dates
3
Professor receives Liley Medal
for revealing NZ’s dramatic rise
in infectious diseases
4
$1.2m high blood pressure trial
funded
5
2013 New Zealand Research
Honours Awards
6
Chief Executive’s message
Royal College honours top Kiwi
paediatrician
6
Virus particles set to help fight
cancer
7
As I write this message there is less than a month before Christmas.
It is still a busy time for us at the HRC, as we have many funding
opportunities in process.
Study identifies significant
gaps in Māori maternal health
knowledge
8
Low blood sugar in newborns –
how low is too low?
10
Secretariat staff news
11
Curing the incurable: exploring
a new protein replacement
therapy
12
Injury researcher wins national
leadership award
13
Licence policy drives research
14
‘The eyes have it’ in top health
research Career Development
Awards
15
Key to brain’s role in fertility
identified
16
HRC Chief Executive, Dr Robin Olds
The 2014 funding round has taken several steps forward since the last
issue of HRC News. All proposals are now undergoing peer review, prior
to being considered by assessing committees in the New Year.
The HRC estimates the total value of proposals to our annual funding
round this year to be about $475 million. We will be able to support
about $65–70 million of contracts. For the five types of contract offered
in the 2014 round, we will likely fund six Feasibility Studies (out of
31 applications), 10 Emerging Researcher First Grants (out of 44
applications), 4–5 Programmes (out of 15 submitted), 3 Explorer Grants
(from 24 submitted) and about 30 Projects (from an initial 351, 100 of
which were selected to put forward full proposals).
The number of Explorer Grant applications is markedly down from the
116 received last year, which indicates that applicants are now more
aware of the special requirements for this particular fund.
I want to thank all involved in the annual funding round, including the
researchers who spend a great deal of time planning and preparing their
applications, research office staff, our very dedicated peer reviewers, and
the HRC Secretariat for making the process run as smoothly as possible.
We recently announced our Career Development Award recipients for
2014. These awards are a fantastic opportunity to help some of New
Zealand’s best and brightest become world-class leaders in their fields.
We also awarded our Liley Medal to Professor Michael Baker from the
University of Otago, Wellington, at the Royal Society of New Zealand’s
Research Honours event last month. Through his research Professor
Baker and his colleagues have challenged the widely held view that as
a country gets wealthier, infectious diseases inevitably decline. You can
read more about Professor Baker’s research in this issue of HRC News.
Finally, I wish all our readers a restful and enjoyable Christmas break.
Meri Kirihimete ki a koe me te whanau.
Dr Robin Olds
Chief Executive
Health Research Council of New Zealand
2
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa
HRC News December 2013
(Continued from page 1)
Dr Wallace also carried out a pilot
study in sheep to help establish
whether babies born preterm, who
frequently become anaemic after
birth, show similar changes to their
heart structure and function as those
who had anaemia in utero.
Almost all babies born preterm will
become anaemic at some point,
a condition known as anaemia of
prematurity.
For the pilot study, anaemia was
induced in sheep delivered preterm.
This resulted in no long-term growth
impairments, but these animals did
have increased levels of haemoglobin
in their blood as adults. There was a
similar increase in haemoglobin levels
in the anaemia-affected participants
from the human study.
“This is a completely novel finding.
We suspect that the cardiovascular
changes as a result of anaemia have
caused the body’s haematological
system to undergo changes too. It
might be the body’s way of trying to
improve cardiac performance. The
similarity of this finding in humans
and sheep leads us to wonder whether
anaemia before term equivalent age,
whether experienced in- or ex utero,
may have similar long-term health
consequences.”
One News presenter Wendy Petrie presents Dr Wallace with the prize for first place in the
University of Auckland’s Exposure competition, an annual university-wide competition to showcase
postgraduate research. Photo courtesy of the University of Auckland.
Further work by other members of
Dr Wallace’s team is now underway
to investigate the effects of anaemia
following preterm birth on long-term
heart structure and function.
Dr Wallace completed this study as
part of her PhD at the University of
Auckland’s Liggins Institute under
the supervision of Distinguished
Professor Jane Harding and Dr
Stuart Dalziel. She would like to
acknowledge the support of her
collaborators, including Professor
Brett Cowan and Associate Professor
Alistair Young (Department of
Anatomy with Radiology, University
of Auckland) who performed the
cardiac MRI scans and complex
coronary blood flow analysis;
Associate Professor Ian LeGrice and
Professor Bruce Smaill (Auckland
Bioengineering Institute); Auckland
cardiologist Dr Nigel Lever; and
Professor Kent Thornburg from the
Oregon Health & Science University
in the US.
Information: Dr Alexandra Wallace
Liggins Institute, the University of
Auckland
✆ +64 021 628 417
[email protected]
Upcoming closing dates
Subscribing to HRC News
For an up-to-date list of all application registration,
opening and closing dates, please go to the HRC
website: www.hrc.govt.nz.
Current and past issues of HRC News can be
viewed on the HRC website: www.hrc.govt.nz.
Ngā Kanohi Kitea Full Project Grant
Online registration closes on 17 December 2013
(12pm)
Applications close on 11 March 2014 (12pm)
Hard copies of full project applications are due at the
HRC by 14 March 2014 (5pm)
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Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa
3
HRC News December 2013
Professor receives medal for revealing
NZ’s dramatic rise in infectious diseases
The HRC’s prestigious Liley Medal was awarded to Professor Michael Baker at the New
Zealand Research Honours Dinner held in Dunedin on 27 November 2013. Sir William Liley’s
widow, Lady Margaret Liley, was again able to present the Liley Medal, along with the HRC’s
Board Chair, Mr Robert Stewart, ONZM, on behalf of the HRC.
Professor Michael Baker
Photograph by Dionne Ward
Professor Michael Baker receives the Liley Medal from Lady Margaret Liley and HRC Board Chair Mr
Robert Stewart at the 2013 New Zealand Research Honours Dinner.
Photograph courtesy of the Royal Society of New Zealand
Professor Baker, from the University
of Otago, Wellington, has been
honoured for his outstanding
contribution to the health and
medical sciences in the field of public
health.
admissions for infectious diseases
between the periods 1989–1993 and
2004–2008. The authors also showed
that Māori and Pacific people and
those who are socioeconomically
disadvantaged bore a disproportionate
share of the burden.
implications for health and social
policy in New Zealand, and will
likely stimulate research and action
in other countries where ethnic and
socioeconomic inequalities may
predispose vulnerable populations to
poor health outcomes.”
“Through this study Professor Baker
and his colleagues have challenged
the widely held view that as a country
gets wealthier, infectious diseases
inevitably decline. Instead, they’ve
shown that in New Zealand we’re
experiencing a double whammy, with
a rise in infectious diseases as well
as chronic diseases such as cancer
and diabetes,” says the HRC’s Chief
Executive, Dr Robin Olds.
Information: Professor Michael
Baker
University of Otago, Wellington
✆ +64 4 918 6802
[email protected]
In 2012, Professor Baker was the
lead author on an already highly
cited paper1 in the world’s leading
general medical journal, The Lancet.
The paper presented a national
study of 5 million overnight hospital
admissions showing a dramatic rise
in the incidence of serious infectious
diseases and rising inequalities across
populations in New Zealand.
The paper uncovered a relative
increase of 51 per cent in the
age-standardised rate of hospital
4
“The findings have enormous
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa
1 Dr Michael G Baker MBChB, Lucy Telfar Barnard
PhD, Amanda Kvalsvig MBChB, Ayesha Verrall
MBChB, Jane Zhang MSc, Michael Keall PhD, Nick
Wilson MBChB, Teresa Wall DPH, Prof Philippa
Howden-Chapman PhD (24 March 2012). Increasing incidence of serious infectious diseases and
inequalities in New Zealand: a national epidemiological study, The Lancet, Vol. 379, Issue 9821,
p1112-1119.
HRC News December 2013
About the Liley Medal
Liley Medal obverse
Liley Medal reverse
The Liley Medal is awarded annually by the Health
Research Council of New Zealand to recognise an
individual whose recent research has produced a
significant breakthrough within the health and medical
fields. The medal is named after Sir William (Bill) Liley
KCMG, BMedSc, MB, ChB, PhD (ANU), Hon. DSc
(VUW), Dip Obs, FRSNZ, FRCOG, Hon. FACOG
(1929–1983), whose contributions to medical science,
particularly obstetrics, while working at National
Women’s Hospital in Auckland are still celebrated
today. One of Sir William’s great contributions was
to extend the use of spectrophotometry of amniotic
fluid to a much wider range of potentially affected
pregnancies – work which gained him an international
reputation. The technique he developed made it
possible to identify which baby could be safely in utero
for a normal gestation period and which baby should
be delivered.
For more information about the Liley Medal and Sir
William Liley, go to the HRC website: www.hrc.govt.
nz/news-and-publications/medals.
$1.2m high blood pressure trial funded
A $1.2 million nationwide project will evaluate how care for people with resistant high blood
pressure1 can be improved in New Zealand. The project will comprehensively assess aspects of
health delivery for people with high blood pressure.
A key part of the two year project will be a trial that will
compare the effectiveness of a comprehensive clinical
management approach with a new treatment that ‘zaps’
nerves to the kidney to reduce blood pressure.
denervation is a very promising technique, but its role
in New Zealand health care is currently uncertain. Renal
denervation is still new in this country and is only available
in certain centres.
The University of Auckland will lead this research, working
with a large team of health professionals from across the
country.
This trial will provide detailed, comprehensive advice for
New Zealand on the optimal ways to help people with
resistant high blood pressure. The trial itself, within this
wider programme of work, will compare the effects of renal
denervation to those of intensive medical management on
blood pressure and other measures of health.
The trial will include several hundred people with resistant
high blood pressure from throughout Auckland, Waikato
and Christchurch.
The funding for the programme comes from the new
Health Innovation Partnership that was established earlier
this year between the National Health Committee and the
HRC.
The five district health boards in Auckland, Waikato and
Christchurch are supporting the trial.
New Zealand Chair of the Cardiac Society of Australia
and New Zealand Professor Ralph Stewart says renal
The trial will be clinically led, with strong participation
from medical and interventional specialists and general
practitioners.
Treating hypertension has been consistently shown to
reduce the risk of cardiovascular disease and stroke, which
are major health targets in New Zealand.
1 Resistant high blood pressure is defined as having a systolic blood pressure
greater or equal to 160mmHg despite taking at least three blood pressure lowering
medications. Normal blood pressure is less than 120mmHg (systolic) and less than
80mmHg (diastolic).
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa
5
HRC News December 2013
2013 New Zealand Research Honours
awards
The HRC would like to congratulate all the health/
science-related winners at this year’s Royal Society of
New Zealand Research Honours event.
Callaghan Medal – Dr Siouxsie Wiles, from the
University of Auckland, in the field of microbiology/
science communication.
Rutherford Medal – Distinguished Professor Dame
Anne Salmond, FRSNZ, from the University of
Auckland in the field of anthropology.
MacDiarmid Medal – Professor Neil Broom, from
the University of Auckland, in the field of health/
bioengineering.
Thomson Medal – Dr Peter Lee, Chief Executive
of Auckland UniServices Limited in the field of
commercialisation.
A full list of the 2013 Research Honours medal winners
can be found at www.royalsociety.org.nz.
Royal College honours top Kiwi paediatrician
Former HRC Board member, Distinguished Professor Jane Harding from the University
of Auckland, is to be awarded the Howard Williams Medal for 2014 at the Royal College of
Physicians Congress in Auckland next May.
announcement was made by the
President of the Paediatrics and Child
Health Division, Associate Professor
Susan Maloney.
Professor Jane Harding served on the HRC
Board between 2001 and 2007.
The college’s Paediatrics and Child
Health Division awards the medal
each year to a person who has made
an outstanding contribution to
Paediatrics and Child Health in
Australia and/or New Zealand.
This may be in the areas of
research, education, teaching,
administration, or in the development
of special services or practice. The
6
Professor Harding’s research activities
include clinical as well as basic
physiological studies. Her main
interests concern the interaction of
nutrients and growth factors in the
regulation of growth before and after
birth, and the long-term consequences
of treatments given around the time
of birth.
Most recently, she was the lead
scientist in a part HRC-funded
study (published in The Lancet in
September) that developed a cheap
and easy-to-administer dextrose gel to
treat low blood sugar (hypoglycaemia)
in newborns (read more about this
study on page 11). In June this year,
Professor Harding was awarded
$1,197,339 in the HRC’s annual
funding round to test the dextrose gel
treatment in a randomised trial.
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa
Professor Harding obtained her
medical degree at the University
of Auckland, and trained in fetal
physiology on a Rhodes Scholarship,
completing her Doctor of Philosophy
at the University of Oxford. After
specialist training as a paediatrician
in New Zealand, she completed her
FRACP in neonatology.
Her postdoctoral training was as a
Fogarty Fellow at the University of
California in San Francisco.
Professor Harding was appointed
to the Medical and Health Sciences
Faculty of the University of Auckland
in 1989 and was appointed Professor
of Neonatology in 1997. She is
currently Deputy Vice-Chancellor
(Research) for the University of
Auckland and is a member of the
LiFePATH research group of the
university’s Liggins Institute.
News article courtesy of the University
of Auckland.
HRC News December 2013
Virus particles set to help fight cancer
By Mark Wright
Virus-like particles (VLPs), based on the empty virus shell of rabbit calicivirus, have now been
developed by University of Otago researchers to the point where they could be trialled to deliver
anti-cancer vaccines and treatments in people.
vaccines, like the hepatitis B vaccine
or the cervical cancer vaccine, target
another arm of the immune response,
which is to make lots of antibodies.”
The calicivirus-based VLP gets picked
up by the dendritic cells. These cells
then present it to the body’s killer T
cells, which then attack the tumour.
Dr Young says one of the key features
is the way they also form a memory
response, just as you would see with
the likes of a hepatitis vaccination.
Associate Professor Sarah Young
Associate Professor Sarah Young, who
was awarded a HRC Sir Charles
Hercus Health Research Fellowship in
2008, says the VLP looks like a virus
to the body’s immune system but it
can’t replicate because it doesn’t have
any genetic material inside it.
“We manipulate that shell of the
virus and put on bits of the tumour
and other immune-activating signals
that will then be able to activate the
immune system. The idea is to trick
your immune system into thinking
that its own tumour is like the virus.”
Dr Young says the work has involved
close collaboration with virologist
Professor Vernon Ward, who makes
the VLP, and immunologist Professor
Margaret Baird, who is an expert in
how the immune system is activated.
“The great thing about this calicivirus
is that it acts differently to other VLPs;
it enhances the killing arm of the
immune response. It induces cytotoxic
immune cells that specifically target
and kill tumour cells.
“Other VLPs that are used in other
“The whole idea with vaccination is
that you’ve got these memory cells
that will hang around your body for
a very long time. If you were ever
infected by hepatitis they would kill
off those virally infected cells, before it
did any damage to your body.”
Working on VLPs has been a longterm project for Dr Young. Her
four-year $500,000 Hercus Fellowship
allowed her to focus on putting
certain immune enhancers on a VLP
to activate particular types of cells
within the immune system.
“A second paper we’re going to publish
shows that you can put this enhancer
molecule on the surface of VLP and
inject it intravenously. It produces a
strong anti-tumour response – much
more than if you don’t have it.”
Dr Young says when it comes to
fighting cancer they use the term
vaccine more loosely. Instead of just
being a prophylactic, given to prevent
disease, they also use the term to
mean a therapy.
“The majority of the patients we want
to treat would use it as a therapy. Once
the patient has the disease we use the
VLP to treat that patient and produce
their body’s own immune response to
that existing tumour.
“At the moment we are looking at how
our VLP would fit in with the current
gold standard therapy. Patients would
come in and have a surgical resection
or some chemotherapy: how would
the use of a VLP work alongside that?”
In many ways the VLP works like
chemotherapy in that it kills off
tumour cells. However, the big
advantage it has is that it shouldn’t
have any side effects.
“Chemotherapy is often a blunt tool.
It blasts anything that is growing. This
is a very specific tool only targeting
specific cells and providing that
memory response.”
Dr Young says they are now at the
stage where they can produce clinical
grade VLPs that would be adaptable
to different tumour models (e.g.
melanoma and lung cancer).
“It works well in all of the settings
we’ve tested it in so far. It could
potentially be a universal treatment,
which is really exciting.”
Dr Young says they are also looking
at cellular therapy. This is where they
grow T cells in the lab, put them back
into the affected animal and then add
the VLP later to boost the immune
response of those T cells.
“You can do many different
manipulations with this vaccine.”
Information: Associate Professor
Sarah Young
University of Otago, Dunedin
✆ +64 3 470 3457
[email protected]
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa
7
HRC News December 2013
At the launch of the Hapū Ora: Wellbeing in the Early Stages of Life study (from left): Kaumatua Pio Jacobs, Dr Angela Moewaka Barnes, Ms Paula Searle,
Associate Professor Joanne Baxter, Associate Professor Helen Moewaka Barnes and Dr Mihi Ratima. Absent: Dr Sue Crengle, Dr Leonie Pihama and Ms
Bridget Robson.
Study identifies significant gaps in Māori
maternal health knowledge
By Suzy Botica
A study released last month
has identified four priority
areas where more research
is needed to better support
Māori mothers and their
babies.
The Hapū Ora: Wellbeing in the Early
Stages of Life study1 looked at factors
affecting Māori health and wellbeing
in the early stages of life (hapū ora),
covering the fetal/gestational and
neonatal periods.
8
Two of the study’s authors, Massey
University’s Associate Professor Helen
Moewaka Barnes and Dr Angela
Moewaka Barnes (both Ngā Puhi),
say the research team wanted to look
beyond individual behaviour and
biology.
“A strongly individual focus can fail
to take into account wider societal
issues and causes of inequities. We’ve
focused on identifying the underlying
environmental influences that are
shaping the lives and experiences
of Māori and influencing maternal
and infant wellbeing,” says Dr Helen
Moewaka Barnes.
Helen and Angela worked with
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa
co-authors Associate Professor
Joanne Baxter (University of Otago,
Dunedin), Dr Sue Crengle (the
University of Auckland), Dr Leonie
Pihama (Māori Indigenous Analysis
Ltd), Dr Mihi Ratima (Taumata
Associates) and Ms Bridget Robson
(Wellington School of Medicine and
Health Sciences).
Each took responsibility for writing
up specific areas, broadly covering:
contextual information; Māori
concepts related to pregnancy and
birth; impacts and influences on
babies in utero and in the early days,
including epigenetics research; stress;
maternal mental health and; antenatal
HRC News December 2013
care, labour and delivery care. These
areas were then worked on collectively
to integrate the report.
The study, which was funded by the
HRC and the Ministry of Health,
based its findings on an extensive
literature review and discussions with
more than 50 Māori stakeholders
from throughout New Zealand. It
identified gaps in knowledge at all
levels of influence: national and
state (macro); community (mezzo);
mothers and babies (micro); and
health services (exosystems).
The mental health of Māori women
during pregnancy and after birth
emerged as an area of particular
concern. The literature review
revealed high levels of mental
health needs among Māori women,
especially young women. There were
also considerable gaps in knowledge.
The authors found no research in
New Zealand that directly examines
discrimination as a contributor
to maternal stress. This is despite
international research that has found
links between racism and pregnancyrelated outcomes.
“There is a dearth of epidemiological
research on stress and the mental
health of Māori women during and
post pregnancy. We found only one
published research paper2 measuring
postnatal depression in Māori,” says
Dr Angela Moewaka Barnes.
Using the knowledge gaps and
needs identified in their review and
stakeholder interviews, the study’s
authors developed four overarching
priority areas for hapū ora. They are:
1. Ensure high quality data as
a foundation for research,
monitoring and evaluation
Data is particularly needed
on Māori birth outcomes, and
maternal mental and physical
health.
2. Address societal conditions
such as poverty and
deprivation, and meet
the needs of vulnerable
populations (e.g., people living
in poverty, teen parents, solo
mothers) The review suggests
that societal norms, systems
and practices can negatively
position pregnant women, new
mothers and whanāu through
stigma, discrimination and
marginalisation.
To view an electronic copy of the
Hapū Ora: Wellbeing in the Early
Stages of Life study, go to www.massey.
ac.nz/massey/learning/departments/
centres-research/shore/projects/hapuora.cfm.
3. Support mother, baby and
whanāu through services and
social support, and by better
understanding stress and
maternal health issues
The review found that maternal
health, wellbeing and behaviours
can have considerable effects
on babies in utero and in the
early days after birth, with
implications throughout their
lives. Maternal mental health,
diabetes, nutrition and substance
use were highlighted as key areas
to focus on.
4. Improve services for maternal
and newborn care, including
maternal mental health care
Māori women experience
inequalities in access to care and
report lower levels of satisfaction
than other women. “There could
be a lot more consistency of care.
We need maternal and newborn
care providers to recognise and
value Māori tikanga, world views
and practices from pregnancy
through to birth,” says Dr Helen
Moewaka Barnes.
Information: Associate Professor
Helen Moewaka Barnes
Whāriki Research Group
Massey University, Auckland
✆ + 64 9 366 6136
[email protected]
Dr Angela Moewaka Barnes
Whāriki Research Group
Massey University, Auckland
✆ +64 9 366 6136
[email protected]
1 Moewaka Barnes, H., Moewaka Barnes, A., Baxter,
J., Crengle, S., Pihama, L., Ratima, M., Robson, B.
(2013) Hapū Ora: Wellbeing in the Early Stages of
Life.
2 Webster, M., Thompson, J., Mitchell, E., Werry, J.
(1994) Postnatal depression in a community cohort.
Australia and New Zealand Journal of Psychiatry,
28(1), 42-49.
3 Kaupapa is a set of principles and ideas that inform
behaviour and customs.
At the launch of the study, the
Ministry of Health’s Manager of Māori
Research, Paula Searle, said it was a
very valuable piece of research and
kaupapa3. It was also timely.
“I think this study will contribute
greatly to the government’s National
Science Challenge ‘A Better Start’,
which will have its first requests for
proposals released early next year. The
findings identify several key factors in
improving hapū ora. Early physical,
social and cognitive development lays
a critical foundation for health and
wellbeing throughout our life,” says
Ms Searle.
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa
9
HRC News December 2013
Low blood sugar in newborns – how low is
too low?
By Suzy Botica
Data analysis from a major New Zealand study into the connection between low blood sugar
levels (hypoglycaemia) and brain damage in newborn babies is now underway. The results are
expected to help guide the care of millions of babies around the world.
Most of the children in the study
were recruited from the Sugar Babies
Study (see box feature on page 11),
which looked at the effectiveness of a
simple dextrose gel to treat low blood
sugars in at-risk babies. Consequently,
Professor Harding’s team knew the
children’s exact blood sugar history
from birth.
“By continuously monitoring the
blood sugar levels of these babies,
we’ve been able to show that there
are a lot more babies with low blood
sugar levels than we know about just
by using routine blood tests,” says
Professor Harding. “Now we need to
find out what blood sugar levels, and
for what duration and frequency, can
cause brain damage.”
Distinguished Professor Jane Harding
University of Auckland Distinguished
Professor Jane Harding heads the
HRC-funded study, which has
involved testing some 400 2-year-old
children born at Waikato Hospital at
risk of low blood sugar levels. The
main aim is to find out if having low
blood sugar levels in the critical
newborn period has an effect on how
children grow and develop later on.
A low blood sugar level in newborn
babies is most common in the first day
or two after birth and occurs in up to
15 per cent of all newborns. Preterm,
small, and big babies are at greater
risk of having low blood sugar levels
along with babies whose mothers
are diabetic. Low blood sugar levels
can sometimes cause brain damage,
including visual problems and
developmental delays.
10
The study team tested the 2-year-old
children for brain function, vision,
cognitive and language development,
memory, growth, general health, and
family environment. In the process,
they’ve developed a number of
world-first techniques for assessing
newborns and 2-year-olds.
One such technique involved teaming
up with Distinguished Professor Geoff
Chase from Canterbury University
to find the best way of analysing and
interpreting the babies’ continuous
glucose monitoring data.
“The instruments that continuously
monitor glucose levels are designed
for diabetics. They don’t measure
well at low levels, which is exactly
what we’re interested in, and don’t
take advantage of the other data
we do have. Therefore, we had to
develop new techniques to analyse
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa
and calibrate the data for newborns.
These techniques will now be used in
future research studies and eventually
in clinical practice,” says Professor
Harding.
The area of the brain most often
affected by low sugar levels is
the visual cortex. Together with
University of Auckland vision scientist
Dr Ben Thompson, the study team
have developed and validated new
methods for assessing visual cortical
function in very young children.
Researchers from the university’s
Auckland Bioengineering Institute
are now working on adapting these
techniques further for clinical use.
“It’s notoriously difficult to test vision
in small children before they can tell
you what they can see. These methods
have the potential to provide the basis
for a reliable and automated way of
assessing vision in young children,”
says Professor Harding.
The team have also developed a
graded battery of tests for assessing
executive function in 2-year-olds
with the help of Dr Trecia Wouldes
from the University of Auckland’s
Department of Psychological
Medicine. This includes measuring
self-control, working memory, and
the ability to learn rules and then to
change them. These are important for
predicting ability to learn and school
performance, but again, are difficult to
measure in 2-year-olds.
Professor Harding says preliminary
findings suggest that children born
at risk of low blood sugars remain
vulnerable to developmental problems
HRC News December 2013
at 2 years of age. She expects the first
results to come through in the first
half of 2014. She has also received a
$2.4 million grant from the National
Institutes of Health (NIH) in the US
to assess the children in this study
Information: Distinguished
Professor Jane Harding
Deputy Vice-Chancellor (Research)
The University of Auckland
✆ +64 9 373 7599
[email protected]
when they turn 4 and a half years
of age.
“All of these data will provide critical
information about how newborn
babies should be monitored and
treated to prevent brain damage.”
Simple gel helps prevent brain damage in newborns
inside of the cheek is more effective
than feeding alone for treating low
blood sugars.
In September this year, the
international medical journal, The
Lancet, published research from the
Sugar Babies Study* showing that a
cheap and easy-to-administer
dextrose gel should be used to treat
low blood sugars in newborns.
University of Auckland study leader
Professor Jane Harding says it’s the
first report in babies to show that
dextrose gel massaged into the
formula feeds, and to be formula fed
at two weeks of age.
“Because this treatment is
inexpensive and simple to
administer, it should be considered
for first-line management of late
preterm and term hypoglycaemic
babies in the first 48 hours after
birth,” says Professor Harding.
The study enrolled at-risk babies
born after 35 weeks’ gestation
from Waikato Women’s Hospital in
Hamilton in the first 48 hours after
birth. Those babies who developed
low blood sugars were randomly
assigned to the dextrose gel or to a
placebo gel.
Treatment with dextrose gel almost
halved the likelihood of treatment
failure compared with the placebo,
with no adverse effects. Babies given
the gel were also less likely to be
admitted to intensive care for low
blood sugars, to receive additional
*Funding for the Sugar Babies Study
came from the Waikato Medical
Research Foundation, the Auckland
Medical Research Foundation, the
Maurice and Phyllis Paykel Trust,
the HRC and the Rebecca Roberts
Scholarship.
News article courtesy of the
University of Auckland.
Secretariat staff news
About HRC News
We are pleased to announce that Jaimee Dudley has
been appointed as a part-time permanent Support
Project Coordinator within the HRC’s Māori Health
Research team. Congratulations Jaimee.
HRC News can be viewed on the HRC website: www.
hrc.govt.nz
Editor: Kristine Scherp
Writers: Suzy Botica
Mark Wright
Email: [email protected]
Postal: PO Box 5541, Wellesley Street
Auckland, 1141, New Zealand
Phone: (09) 303 5200
Fax:
(09) 377 9988
Contributions are welcome. All articles in HRC News
may be reprinted, provided the writer and the source
are acknowledged.
ISSN 1178-9565 (Print) ISSN 1178-9557 (Online)
Pauline Curtis has been appointed as Policy Analyst
to cover for Rebecca Luther in the Research Policy,
Strategy and Evaluation team while Rebecca is
on parental leave. Pauline starts in the role on
Wednesday, 15 January 2014. Welcome back to the
HRC Pauline.
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa
11
HRC News December 2013
Curing the incurable: exploring a new
protein replacement therapy
By Suzy Botica
Associate Professor Geoffrey Krissansen is one of the first recipients of the inaugural HRC
Explorer Grants. Although just 6 months have passed since the grant recipients were
announced, Dr Krissansen and his colleagues at the University of Auckland are excited about
the prospects of their new drug delivery platform designed to combat certain incurable genetic
disorders.
Both cystic fibrosis and HDGC are
associated with high morbidity and
lead to premature death.
The Xentry drug delivery platform,
which is patented by the University
of Auckland, is being employed to
replace mutated proteins encoded by
single genes with the normal proteins.
Dr Krissansen says that part of
what makes Xentry so special is its
extremely small size and unique
structure.
Associate Professor Geoffrey Krissansen
Dr Krissansen’s research team have
developed a novel drug delivery
platform based on a cell-penetrating
peptide called Xentry, which is
derived from the hepatitis B virus.
Xentry can be used to deliver drugs
directly to layers of cells called
epithelia. These cells line organs and
glands such as the skin, and
respiratory and gastrointestinal tracts.
Funds from the Explorer Grant
are helping the team test whether
Xentry-based technologies could
potentially combat two particularly
cruel incurable diseases arising from
single gene defects: cystic fibrosis,
which affects epithelia in the lungs,
and hereditary diffuse gastric cancer
(HDGC), which affects epithelia in
the stomach.
12
“Large molecules don’t get across the
plasma membrane of cells, which is a
big problem for the pharmaceutical
industry. If you can’t get inside the
cell, then you can’t reach many
potential drug targets,” says Dr
Krissansen.
“Xentry is a tiny peptide. Its
functional core is only four amino
acids long, whereas most other cellpenetrating peptides are made up of
between 10 and 20 amino acids. It’s
also a new class of cell-penetrating
peptide that can make its way across
the cell membranes of virtually any
cells – except, unlike all other cellpenetrating peptides, circulating
blood cells. This is a distinct advantage
because it means the peptide doesn’t
get diluted by blood cells following
intravenous delivery.”
The team’s studies in mice have shown
that Xentry is taken up very strongly
into epithelial cells lining the stomach,
bowel, and lung.
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa
In the case of cystic fibrosis, mutations
in the cystic fibrosis transmembrane
conductance regulator (CFTR) gene
disrupt its function, which leads
to mucus build up in the lungs. Dr
Krissansen and his team plan to
replace the mutated CFTR protein
with a normal protein by using Xentry
to deliver therapeutic cargoes by an
intravenous route.
“It’s believed that you would only need
to restore 10 per cent of the CFTR
protein’s activity back to normal to
treat someone with cystic fibrosis,”
says Dr Krissansen.
HDGC is a whole different scenario
though, says Dr Krissansen. Whereas
with cystic fibrosis you inherit a
copy of the defective gene from both
your mother and father, with HDGC
you only need to inherit a defective
E-cadherin gene from either your
mother or your father. Even though
you still have a ‘good’ copy of the gene,
this can be deactivated to become
‘bad’ – and does so in about 80 per
cent of cases.
Dr Krissansen’s research team is
seeking to use the Xentry peptide to
deliver a good copy of the E-cadherin
gene to HDGC patients. This poses
a real challenge because all of the
epithelial cells in HDGC patients’
stomachs have a copy of the bad gene.
This means they need to restore the
epithelial cell function of as many cells
as possible. The more cells they can
repair, the lower the risk of cancer.
HRC News December 2013
cargoes into the cell. We’re now trying
to improve its release from the cell’s
endosomes into the cytoplasm.”
Dr Krissansen says they are trying
to see how far they can push the
technology.
Master’s student Jason Michael (right) is working on the cystic fibrosis project with Dr Krissansen, while
PhD student Glenn Bell (left) is working on the hereditary diffuse gastric cancer project. PhD student
Kristopher Montrose and technician Yi Yang (not pictured) performed the pioneering work on the
development of the Xentry peptide.
To date, Dr Krissansen’s team have
a cell line from both a cystic fibrosis
patient and a HDGC patient, and
are testing whether they can restore
the expression of the CFTR and
E-cadherin genes in these cells. Once
they’ve finished the cellular studies,
they plan to move onto animal studies,
hopefully towards the middle of 2014.
“It’s still only early days, but I
personally believe cell-penetrating
peptide technology will eventually
transform medical practice.”
Information: Associate Professor
Geoffrey Krissansen
Department of Molecular Medicine
and Pathology, the University of
Auckland
✆ +64 9 373 7599 ext 86280
[email protected]
“We know Xentry can deliver large
Injury researcher wins national leadership award
The Te Manaia Leadership Award
recognises the outstanding
commitment and contribution
individuals and organisations make to
the national injury prevention sector.
The award is convened by the Injury
Prevention Network of Aotearoa New
Zealand.
“Shanthi has made an outstanding
contribution to the injury prevention
community, both in New Zealand and
internationally, through her research
and workforce development activities,”
says Injury Prevention Network
General Manager Justine Ropata.
Professor Shanthi Ameratunga (right) with Injury
Prevention Network Chair Kiri Pardoe
The HRC extends its warmest
congratulatons to Professor
Shanthi Ameratunga, the
2013 recipient of the Injury
Prevention Network Te
Manaia Leadership Award.
“She has achieved to the highest
level in her academic career and
has been passionately committed to
training and stimulating the work of
practitioners and future leaders in the
field. It is for these reasons that she
is a worthy recipient of a Te Manaia
Leadership Award.”
Professor Ameratunga is a
leading injury researcher who has
achieved international acclaim.
Her current research work focuses
on road traffic injuries, child and
youth injury, disability and highquality equitable trauma care and
rehabilitation outcomes. She is
first named investigator on two
current HRC-funded projects, one
looking at the determinants of lifethreatening injuries among young
and middle-aged adults, and the
other a randomised controlled trial
to investigate the effectiveness of an
innovative mobile phone intervention
to reduce hazardous drinking in atrisk groups.
Professor Ameratunga is currently
professor of epidemiology at the
University of Auckland’s School of
Population Health.
In New Zealand unintentional and
intentional injury is the leading cause
of death for people between the ages
of 1 to 34 years, and a major cause of
hospitalisation.
News article courtesy of the Injury
Prevention Network of Aotearoa New
Zealand.
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa
13
HRC News December 2013
Licence policy drives research
By Mark Wright
If you are looking for a textbook example of research being used to shape policy then it is hard to
go past the HRC-funded New Zealand Drivers Study.
the study became part of a wider
HRC-funded Injury Prevention
Research Unit programme. By that
stage the New Zealand Drivers Study
had gone on to look at those drivers
who hadn’t actually progressed on to
get their restricted licence.
“A lot had just got ‘stuck’ on their
learner licence. They hadn’t gone
on to get their restricted licence
and we weren’t sure why. We didn’t
know whether they were doing a
lot of unsupervised driving and
just ignoring the learner licence
conditions, or whether they weren’t
driving at all,” says Dr Begg.
Dr Rebecca Brookland (left) and Dr Dorothy Begg
Photo courtesy of the University of Otago Magazine
Run as part of a HRC-funded
programme at the University of
Otago, Dunedin’s Department of
Preventive and Social Medicine’s
Injury Prevention Research Unit, the
New Zealand Drivers Study can be
traced back to a pilot study in 2001.
That eventually led to the 2005 launch
of the full study with funding from the
HRC, the Accident Compensation
Corporation, and the Road Safety
Trust.
Since that time it has helped provide
evidence and generate debate about
young drivers and the country’s
licensing system. But for principal
investigator Dr Dorothy Begg one of
the most important things has been
the way the research has fed into the
development of policy.
“The actual purpose of the study
was to provide evidence to influence
young driver policy in New Zealand.
That was what we set out to do
because we could see there was a big
gap there,” she explains.
14
Dr Begg says they originally had the
funding for four years. However, a
longer timeframe was needed to make
the project work, especially when the
recruitment phase required two years
to recruit a comprehensive sample
of 4000 newly licensed drivers from
throughout New Zealand.
One of the first things they looked at
was the licensing age and attitudes
to raising it. Although they expected
their cohort to be against the idea,
more than half were actually in favour
of the age being raised.
“The main reason they were getting
their licence wasn’t for what you
might call essential travel. It was
mainly so they could go where they
wanted and have freedom to do what
they wanted to do. Independence.”
That paper helped provide evidence
to go to the Parliamentary Select
Committee when they met to discuss
raising the driver licensing age, which
they went on to do.
After the first four years of funding,
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa
“From the follow-up interviews of
those that hadn’t got their restricted
licence we found that most of them
weren’t driving very much at all – so
they weren’t just ignoring the licensing
law. That was a little surprising.”
The study also included interviews
with 1200 parents of restricted drivers.
Dr Rebecca Brookland, who
undertook that part of the study for
her PhD, says parents were keen to
have the opportunity to talk about the
issues they faced.
“They felt challenged by finding
that balance between giving their
adolescents independence and
their concerns about the crash risk
and safety issues of them driving
unsupervised.”
It helped Dr Brookland identify the
key things that parents were doing
that would influence their teen’s
risk of having a crash or regularly
breaching the conditions of their
graduated driver licence. Those key
things included parents having a crash
themselves; having less rules around
their adolescent’s driving; and their
HRC News December 2013
adolescent having easy access to a
vehicle.
Findings from the parent study have
contributed to the development of
the New Zealand Transport Agency’s
current ‘Safe Teen Driver’ campaign,
which encourages parents to stay
actively involved in their teen’s driving
during their restricted licence period.
Study findings have also been used by
the New Zealand Transport Agency
in the development of their ‘Safe Teen
Vehicle’ resources.
“The restricted licence stage is still a
period of learning for a young driver,”
says Dr Brookland. “Crash risk is
highest in the first six months of
getting your restricted licence.”
Current moves to extend the period of
learner licensing from six months to
a year has the support of Dr Begg and
her team.
“Our research would suggest that it is
a good idea. Dr Pauline Gulliver had
a paper published looking at driver
training and supervised driving at the
learner licence stage.
“She found that time was a key factor.
Learner drivers who spent longer on
their learner licence had a lower crash
risk when driving on their restricted
licence, so we would advocate for an
extended learner licence period.”
Dr Dorothy Begg
University of Otago, Dunedin
✆ 021 1222312
[email protected]
‘The eyes have it’ in top health research
Career Development Awards
Three of New Zealand’s talented, up-and-coming eye researchers have each received up to
$500,000 from the HRC to develop exciting new therapies for debilitating eye conditions such
as cataracts and diseases of the cornea.
The trio and 11 other researchers
have collectively been awarded
more than $4.3 million through the
HRC’s 2014 Career Development
Awards programme. The HRC has
also awarded a further 19 Career
Development Awards in the area of
Māori health (worth a total of $1.5
million) and 10 Career Development
Awards for Pacific health research
(worth a total of $1.09 million).
Eye surgeon and clinician Associate
Professor Dipika Patel from the
University of Auckland will use her
HRC Clinical Practitioner Research
Fellowship to further develop a
new scaffold that could become a
substitute for human corneal tissue.
Ultimately, the scaffold would replace
human donor corneas in transplant
operations.
Donor corneal tissue is a limited
resource in most countries. The
current waiting time for cornea
transplantation in New Zealand is
more than a year. In many other
countries, donor corneal tissue isn’t
available.
“The development of a suitable tissue
substitute would have a dramatic
effect on reducing waiting times
for surgical treatment and may
enable treatment of corneal diseases
that are not currently suitable for
transplantation,” says Dr Patel.
the information needed to develop
novel anti-cataract therapies that use
nutritional supplements to delay the
progression of the cataract on the eye’s
lens.
University of Auckland eye specialist
Dr Ilva Rupenthal plans to use her
Sir Charles Hercus Health Research
Fellowship to develop biodegradable
eye implants that can slowly release
medication for eye diseases over up
to six months. Non-invasive laser
light passed through the cornea will
activate the implants to provide topup doses of medication.
If successful, she says this work will
open up a wide range of avenues in
the field of tissue engineering and
reconstructive surgery.
Dr Angus Grey from the University
of Auckland has received a Sir
Charles Hercus Health Research
Fellowship to tackle cataracts, the
world’s most preventable form
of blindness. Dr Grey will use
his expertise in imaging mass
spectrometry to discover what role
small molecules and metabolites
(substances produced during
metabolism) play in the development
of cataracts.
“These awards are a fantastic
opportunity to help some of New
Zealand’s best and brightest become
world-class leaders in their fields,
and to translate cutting-edge research
from bench to bedside,” says HRC
Chief Executive Dr Robin Olds.
Each year some 16,000 cataract
surgeries are performed in New
Zealand.
Dr Grey says the research will provide
Check out www.hrc.govt.nz/fundingopportunities/recipients for details on
all of the Career Development Award
recipients, including those who have
received an award in the areas of
Māori and Pacific health.
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa
15
HRC News December 2013
Key to brain’s role in fertility identified
By Mark Wright
A key to understanding the brain’s role in triggering fertility has been identified through HRCfunded research at the University of Otago, Dunedin’s Centre for Neuroendocrinology, and
published in the prominent international journal Nature Communications.
Although it was already known that
kisspeptin is important in fertility,
researchers’ understanding of how and
where it worked was still unclear.
“It’s quite a black and white result. We
can now say that kisspeptin signalling
at the GnRH neuron is the key for
fertility.”
Professor Herbison says kisspeptin
signalling was thought to occur in
the brain as well as in the pituitary
gland, the ovaries, the testes, and the
placenta.
He says kisspeptin has been
evolutionarily conserved for
reproduction for billions of years.
“What we didn’t know was what
the relative importance was. Is the
kisspeptin signalling in the ovaries
really the important thing, or is it the
kisspeptin in the brain that’s critical?”
They set up a range of experiments
using strains of genetically
manipulated mice in which the
kisspeptin receptor Gpr54 had been
removed from the small population
of about 1000 GnRH neurons in the
brain. As a result those mice do not
go through puberty and were left
completely infertile.
Professor Allan Herbison
Led by neuroscientist Professor Allan
Herbison, the research has provided
clear proof of the critical part played
by kisspeptin, a small signalling
protein that acts on the gonadotropinreleasing hormone (GnRH) neurons
in the brain. The landmark discovery
opens the door to new fertility
treatments and new forms of
contraception.
“That tells us that the kisspeptin
signalling for GnRH cells is absolutely
critical for fertility. But the clincher
experiment is where you take a mouse
where kisspeptin signalling has been
taken out of every zone on the body,
and put the correct functioning
kisspeptin receptor back into just the
GnRH neurons.
“Now the only place where kisspeptin
can act is on the GnRH neurons.
Amazingly, those mice go through
puberty and become fertile,” he says.
Professor Herbison says this one
small population of cells in the brain
tell the pituitary what to do, and the
pituitary tells the ovaries or the testes
what to do.
“You can go right back to invertebrates
and find kisspeptin is a key molecule
that is required for fertility. When you
come across something that evolution
hasn’t changed much you know you
are onto something that is pretty
important.”
Professor Herbison says the focus
is now switching to how to use
kisspeptin more effectively in fertility
treatment, even though only a small
percentage of people are infertile
because of issues with kisspeptin
signalling in the brain.
“These studies have shown us that
kisspeptin signalling is very important
and can override other causes of
infertility because it is such a powerful
activator of the whole system.”
They are already planning work with
clinical partners on making kisspeptin
part of IVF treatment cycles.
Professor Herbison says there is
also scope to develop a kisspeptin
antagonist. This could have a
role in developing new forms of
contraception and may also have
relevance to diseases such as prostate
cancer in which testosterone is a key
driver.
Professor Allan Herbison
University of Otago, Dunedin
✆ +64 3 479 7312
[email protected]
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa