Download March 2013 Monitoring International Trends

Monitoring International Trends
posted March 2013
The NBA monitors international developments that may influence the management of blood
and blood products in Australia. Our focus is on:
 Potential new product developments and applications;
 Global regulatory and blood practice trends;
 Events that may have an impact on global supply, demand and pricing, such as changes
in company structure, capacity, organisation and ownership; and
 Other emerging risks that could potentially put financial or other pressures on the
Australian sector.
A selection of recent matters of interest appears below.
Table of Contents
Products................................................................................................................................ 1
Regulatory matters ................................................................................................................ 2
Market structure and company news ..................................................................................... 4
Country- specific events ........................................................................................................ 5
Safety and Patient Blood Management ................................................................................. 6
Infectious Diseases ............................................................................................................... 7
Appendix: Alzheimer’s Research .......................................................................................... 9
1. Products
Here the NBA follows the progress in research and clinical trials that may within a
reasonable timeframe make new products available, or may lead to new uses or changes in
use for existing products.
Clotting factors
a) Baxter in February submitted a biologics license application (BLA) supplement to the
US Food and Drug Administration (FDA) for the approval of prophylaxis with FEIBA
NF (anti-Inhibitor coagulant complex), nanofiltered and vapour heated, in patients
with haemophilia A or B and inhibitors.
b) The FDA in March accepted Biogen Idec’s BLA for the marketing approval of its
recombinant factor IX Fc fusion protein (rFIXFc) for treating haemophilia B. The
application included results from the B-LONG phase III clinical trial. This
demonstrated that rFIXFc provides longer-lasting protection from bleeding with fewer
treatments than are required with the current standard of care.
c) Biogen also submitted to the FDA its BLA for its long- lasting recombinant factor VIII
Fc fusion protein (rFVIIIFc) to treat haemophilia A. Biogen Idec stated, "In our phase
III study, patients treated with rFVIIIFc were able to inject rFVIIIFc once-weekly to
twice-weekly, which creates the potential for those currently on prophylactic
treatment to reduce injections by 50 to 100 per year. Moreover, patients currently
treating bleeding episodes could potentially dose prophylactically once per week and
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maintain significant protection from bleeding with about the same total number of
injections each year they use to treat bleeding episodes today."
Other
d) The FDA has approved a 40g (400 ml) vial size for Privigen, immune globulin
intravenous (human), for treatment of primary immunodeficiency and chronic immune
thrombocytopenic purpura.
e) At the 2013 annual meeting of the American Academy of Allergy, Asthma &
Immunology (AAAAI), data were presented showing CSL Behring’s Berinert, C1
esterase inhibitor (human), provides significant relief from cutaneous attacks of
hereditary angioedema (HAE). Also at the Academy meeting, CSL Behring
announced the results of a cost-effectiveness analysis which they said showed that
on-demand treatment of HAE attacks with Berinert provides cost savings to payers
when compared with the use of two other therapies approved in the US for the acute
treatment of HAE, Firazyr and Kalbitor
f) A team from the University of Michigan Medical School has found that an
antidepressant drug used for decades - tranylcypromine, or TCP - may be useful in
treating sickle cell disease1.
g) Hydoxyurea is currently the only FDA-approved medication for sickle cell anemia. It
reduces the pain and organ damage caused by sickled blood cells; it is inexpensive.
Not all patients respond to it, but it now appears response may be able to be
predicted through genetic analysis.
h) Targeted Medical Pharma unveiled new results from an open label study of its oral
amino acid-based erythrocyte stimulating system (ESS) for the treatment of chronic
anaemia. The system is designed to stimulate progenitor stem cells in the bone
marrow.
i) The FDA has accepted for review AMAG’s supplemental new drug application
(sNDA) for iron deficiency anaemia therapy -- Feraheme (ferumoxytol) injection for
intravenous (IV) use. Approval would expand the indication for ferumoxytol beyond
the current indication for the treatment of iron deficiency anaemia (IDA) in adult
patients with chronic kidney disease (CKD) to adult patients with IDA who have failed
or could not take oral iron treatment.
2. Regulatory
The NBA monitors overseas regulatory decisions on products, processes or procedures
which are or may be of relevance to its responsibilities.
a) In February, Europe’s Committee for Medicinal Products for Human Use (CHMP)
adopted a positive opinion recommending a variation to the terms of the marketing
authorisation for CSL Behring’s Privigen2.
b) The FDA has expanded the indication for Corifact, fXIII concentrate (human). In
2011 Corifact was approved in the US for the routine prophylactic treatment of
congenital f XIII deficiency. Its indications now include the peri-operative
1
Lihong Shi, Shuaiying Cui, James D Engel, Osamu Tanabe.”Lysine-specific demethylase 1 is a
therapeutic target for fetal hemoglobin induction”. Nature Medicine, 2013; DOI: 10.1038/nm.3101
2
The new indication is as follows: Immunomodulation in adults, and children and adolescents (0-18
years) in chronic inflammatory demyelinating polyneuropathy (CIDP). Only limited experience is
available of use of intravenous immunoglobulins in children with CIDP.Detailed conditions for the use
of this product will be described in the updated summary of product characteristics (SmPC), which will
be published in the revised European public assessment report (EPAR), and will be available in all
official European Union languages after the variation to the marketing authorisation has been granted
by the European Commission.
2
c)
d)
e)
f)
g)
h)
i)
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management of surgical bleeding in adult and paediatric patients with congenital fXIII
deficiency.
The FDA has granted orphan drug status to Pluristem Therapeutics for its PLacental
eXpanded (PLX) cells for the treatment of aplastic anemia.
Affymax and Takeda Pharmaceutical, which jointly market the drug, Omontys, or
peginesatide, to treat anaemia in patients undergoing kidney dialysis, recalled all lots
of the product after reports that it had caused severe allergic reactions, including
some that were fatal. The FDA announced 19 reports of anaphylaxis. Three of the
patients had died.
The FDA sent a warning letter to Novo Nordisk concerning inadequacies it perceived
during an inspection of a facility in Denmark.
The FDA again rejected rivaroxaban (Xarelto) to treat patients with acute coronary
syndromes (ACS). Janssen Pharmaceuticals in March received a second "complete
response letter," which generally means the FDA requires more data. Bayer
HealthCare partnered with Janssen to develop rivaroxaban.
The FDA has granted orphan drug status3 to ProMetic's plasma derived plasminogen
for the treatment of hypoplasminogenemia, or type I plasminogen deficiency (T1PD)4.
With intravenous immunoglobulin (IVIg) being trialled as a treatment for Alzheimer’s
disease, there is concern that a positive result could put pressure on limited supply of
the product. The FDA is now proposing to lower the hurdle drug developers will face
in gaining approval for Alzheimer’s drugs. So far, the FDA has expected developers
to demonstrate improvements in both cognition and function. Patients have had to
demonstrate improved memory and acuity compared with a placebo group and also
do better at tasks like dressing. The FDA is now planning guidances on trial designs
that can focus on cognitive improvements alone or on preventive measures proved
with biomarkers5. A short summary of some recent Alzheimer’s research is provided
in an Appendix.
Tenaxis Medical has received FDA approval to market its ArterX surgical sealant for
prophylactic use and for treating bleeding after clamp release. ArterX is designed for
use in vasculature reconstruction in a range of surgical procedures. It is a two-part
liquid system that when mixed and applied to the vasculature will transform into a
In the US, orphan drug status is given to drugs or biologics that treat a condition affecting fewer than
200,000 patients nationally. The designation gives the drug developer a seven year period of national
marketing exclusivity, upon marketing approval for the designated indication. It gives tax credits for
clinical research costs, the right to apply for annual grant funding, assistance with clinical trial design
and the waiver of prescription drug user fees.
4
T1PD is an autosomal recessive disorder that leads to fibrous depositions on mucous membranes
throughout the body, affecting eyes, ears, sinuses, tracheobronchial tree, genitourinary tract and
gums.
5
Writing in the New England Journal of Medicine, the FDA noted that "the premise that effective
cognitive improvement will be manifested in the functional assessment of patients is untenable in the
case of early-stage Alzheimer's disease, which is increasingly the target of drug-development efforts.
We simply do not yet have drug-development tools that are validated to provide measures of function
in patients with Alzheimer's disease before the onset of overt dementia."
"For patients whose disease is at an even earlier clinical stage, so that functional impairment would
be more difficult to assess, it might be feasible to approve a drug through the FDA's accelerated
approval pathway on the basis of assessment of cognitive outcome alone. The accelerated-approval
mechanism allows drugs that address an unmet medical need to be approved on the basis of a
surrogate end point or an intermediate clinical end point (e.g., a sensitive cognitive measure), with the
stipulation that post approval studies will be conducted to verify the clinical benefit. Such a regulatory
process may hold promise for facilitating the approval of treatments that appear to be effective in early
Alzheimer's disease, when patients might be expected to derive the greatest benefit."
3
flexible gel in under 15 seconds. Results of the clinical trial appeared in the Annals of
Vascular Surgery.
3. Market structure and company news
The NBA’s business intelligence follows company profitability, business forecasts, capital
raisings or returns, mergers and takeovers, arrangements for joint research and/or
development, contracts for supply of manufacturing inputs, and marketing agreements.
Companies considered include suppliers, potential suppliers and developers of products
which may be of interest.
a) Cangene has purchased commercialization rights from bankrupt Inspiration and its
partner Ipsen to IB1001, a recombinant factor IX (rFIX) currently under review by US
and European regulators for treatment and prevention of bleeding in patients with
haemophilia B. Cangene also acquired Inspiration’s rights to two preclinical drug
candidates IB1007 (recombinant FVIIa) and IB1008 (recombinant FVIII).
b) Cangene reported its results for the second quarter of 2013, ending January 31,
2013. Total revenues for the quarter were $C 25.9 million, less than the $C 33.6
million in the same quarter of 2012. The decrease included a $C 9.7-million reduction
in revenue from US government stockpiling and lower revenue for WinRho SDF.
Partially offsetting these declines was a $C 4.0-million increase in vaccinia immune
globulin (intravenous) revenue. Net loss for the current quarter was $C 3.3 million,
an improvement from a net loss of $C 3.9 million in the same quarter of 2012.
c) A technology targeting Alzheimer's disease has been developed at The University of
British Columbia (UBC) and licensed to Cangene Corporation. Dr.Neil Cashman's
discovery will allow Cangene to advance an immune therapeutic treatment approach
to Alzheimer's by targeting the toxic form of Amyloid-beta with the potential to directly
impact the disease mechanism of action. Dr. Cashman is an expert in misfolded
protein diseases. Dr. Laura Saward, Cangene's Chief Scientific Officer, says "While
this work is in its early stages, it is showing promise for the development of a novel
immunotherapy to address this devastating disease and fits Cangene's refocused
strategy".
d) Grifols reported a 46 per cent increase in sales in 2012 over 2011, following its
acquisition of Talecris. Profits rose some 500 per cent.
e) Cerus Corporation announced financial results for the fourth quarter and year ended
December 31, 2012. The company had year-on -year product revenue growth of 20
per cent. INTERCEPT Blood System disposable kit demand was up 28 per cent
from 2011.
f) Kamada in 2012 posted its first profit from operations. Revenue rose 22 per cent to
$US 72.7 million in 2012 and the company posted a net profit of $US 260,000
compared with a net loss of $US 3.7 million in 2011. Kamada's lead product is
Glassia, an intravenous treatment for alpha-1 antitrypsin deficiency (AAT deficiency)
in congenital emphysema. A milestone in 2013 will be obtaining the results of a
Phase II /III clinical trial in Europe for inhalable AAT, due in December. Kamada will
commence a Phase II clinical trial of inhalable AAT in the US in mid-2013.
g) Kamada is planning to trial its AAT in Type 1 diabetes. The company hopes ".. that
the product can go directly to a Phase III clinical trial, because it is already registered
for
treating AAT deficiency in the US, Brazil, Argentina, and Israel, and we
believe that at least in some of these markets, we can go directly to advanced
studies " The AAT protein already has FDA orphan drug status. Kamada's
distribution agreement with Baxter for Glassia can be expanded to the AAT protein
for diabetes. If Baxter exercises this option, it will accept most of the cost of a US
clinical trial.
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4. Country- specific events
The NBA is interested in relevant safety issues which arise in particular countries, and also
instances of good practice. We monitor health issues in countries from which Australia’s
visitors and immigrants come.
a) In the US, the Obama administration called for open access to the results of federally
funded research. John Holdren, chief of the White House Office of Science and
Technology Policy, directed federal agencies that spend more than $US100 million
annually on research and development to devise a plan to implement public access.
The National Institutes of Health already has an open-access policy in place. The
Holdren memo directed agencies are to ensure that papers stemming from research
they fund should be freely available to the public within a year of publication.
d) The UK’s new Diamond Light Source in Oxfordshire is to analyse viruses requiring
Containment Level 3 – including AIDS, hepatitis and some types of flu. They will be
analysed at atomic and molecular level using the synchrotron light facility, which they
hope will help develop new treatments and vaccines.
e) In Canada, a private company- Canadian Plasma Resources- announced that it plans
to establish plasma collection operations in Toronto and Hamilton and that it will buy
plasma. Currently, Canadian Blood Services and Héma-Québec buy immunoglobulin
in the US and Europe. Cangene in Winnipeg has paid specialty plasma donors for
decades, to provide antibodies used to create Rh immune globulin. A number of
groups, including Canadian Doctors for Medicare, have called on the federal
government to deny approval to Canadian Plasma Resources. Provincial health
ministers are reportedly concerned about the impact on the voluntary donation
system.
f) Taiwan is making publicly funded H5N1 vaccine available for high-risk people such as
coastguardsmen, disease control medical personnel, airport security agents and
individuals who are going to epidemic areas.
g) The Swiss Red Cross announced in February that it is reducing its supply of donor
blood to Greece because bills have not been paid on time.
h) The French senate in December 2012 passed a law unilaterally banning the use of
tubes containing di (2-ethyhexyl) phthalate (DEHP) from paediatric, neonatal and
maternity wards. The ban will take effect from July, 2015, unless the European
Commission takes action against France if the European Food and Safety Authority
(EFSA)’s investigation into DEHP finds the ban is not scientifically justified. That
report is expected in May.
i) Ireland’s Health Minister announced in March that the country’s blood service will
continue permanent donor deferral for men who have sex with men (MSM).
j) The annual Royal College of Surgeons in Ireland Research Day was told how cancer
cells 'hijack' platelets, enabling cancer to spread around the body and promote the
growth of new tumours.
k) In New Zealand, Christchurch recorded a fourfold increase in infectious syphilis from
2011 to 2012. Most men who caught syphilis in 2011 were in their mid-40s and
contracted the disease at sex-on-site venues, such as brothels. In 2012 the median
age dropped to 26, with some sufferers as young as 19. Canterbury District Health
Board Sexual Health Centre physician Dr Heather Young said: "The highest number
of people contracting infectious syphilis is men having sex with men and many are
using social media sites or smartphones to search for sexual partners." The
applications enabled men to meet "anywhere safe and convenient" for casual sex.
One of the big concerns was syphilis' potential to spread into the heterosexual
community where it can be transferred from mother to baby during pregnancy.
Congenital syphilis could result in miscarriages, stillbirths and abnormalities in babies,
she said. Dr Ed Coughlan, clinical director of the Sexual Health Centre, said doctors
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around the city had been alerted and an advertising campaign was being published
on Facebook and in homosexual magazines, he said.
5. Safety and patient blood management
We follow current issues in patient safety.
a) In a report published online in Anesthesia & Analgesia, Johns Hopkins investigators
led by Steven M. Frank, M.D. say red cells in blood stored longer than three weeks
lose the flexibility necessary to squeeze through the body’s smallest capillaries to
deliver oxygen to tissue6. They found these changes are “not readily reversible after
transfusion”.
b) At the American College of Cardiology meeting in San Francisco, results were
presented from a new study that found transfusing donated blood more than three
weeks old results in impaired blood vessel function . The authors7 suggest why older
blood might be detrimental to patient health: a deficiency in nitric oxide which is short
lived but when present relaxes blood vessels.
c) Also at the American College of Cardiology meeting in March, researchers from the
Cleveland Clinic and Sahlgrenska University Hospital (Sweden) reported that
darbepoetin alfa - commonly used to treat anaemia in heart failure patients - does not
improve patients' health does not reduce their risk of death from heart failure. Results
were published simultaneously online by the New England Journal of Medicine.
d) Patients with major bleeding after procedures to open blocked heart arteries are at
significantly increased risk of death, according to a new study published in the March
13 issue of the Journal of the American Medical Association. The researchers also
said there are ways to predict a patient's risk of bleeding after percutaneous coronary
intervention and the risk should be reduced through the use of drugs or other
methods.
e) A meta-analysis8 suggested that using hydroxyethyl starch for critically ill patients
who required volume resuscitation was associated with higher mortality compared
with using other fluids.
f) hysterectomiesrobotic assistance increased from one in 200 procedures in 2007 to
almost one in 10 in 2010, according to a new study led by. Dr. Jason Wright from
Columbia University9. They found this did not reduce post- surgery complications.
There was also no difference in patients’ chances of receiving a blood transfusion.
g) Dr. Sam Schulman of McMaster University in Ontario led studies of more than 2,800
patients who had venous thromboembolism10. In one, Pradaxa was compared with
warfarin, and in the other Pradaxa was compared with placebo. Researchers found
that 1.8 per cent of patients taking Pradaxa had recurrent clots, compared with 1.3
per cent of patients taking warfarin. Fewer patients taking Pradaxa had major
bleeding compared with those taking warfarin (13 against 25). Three patients taking
Pradaxa developed clots, compared with 37 patients taking placebo. The study was
funded by the manufacturer of Pradaxa, Boehringer Ingelheim.
6
“Decreased Erythrocyte Deformability After Transfusion and the Effects of Erythrocyte Storage
Duration”, Anesthesia and Analgesia, published online Feb 28 2013
7
The presenter was Robert Neuman, MD. cardiovascular research fellow; senior authors included
Arshed Quyyumi, MD, professor of medicine and director of the Emory Clinical Cardiovascular
Research Institute, and John Roback, MD, PhD, associate professor of pathology and laboratory
medicine and medical director of the Emory University Hospital blood bank.
8
By Ryan Zarychanski, MD, of the University of Manitoba in Winnipeg, and colleagues, reported in
the Feb. 20 issue of the Journal of the American Medical Association.
9
Journal of the American Medical Association, online February 19, 2013.
10
published Feb. 21 in the New England Journal of Medicine
6
h) French investigators reported11 that kidney transplant patients faced an elevated risk
of cardiovascular events where they had had pre-transplant cytomegalovirus (CMV)
exposure and post-transplant CMV replication. .
6. Infectious diseases
The NBA takes an interest in infectious diseases because: the presence of disease in
individual donors (e.g. influenza), or potential disease resulting from travel (e.g. malaria)
means a donor must be deferred; temporary disease burden within a community (e.g.
dengue in North Queensland) may limit blood collection in the community for a time; and
some people may not be permitted to donate at all (e.g. people who lived in the UK for a
period critical in the history of vCJD). Blood donations are tested for a number of diseases
(e.g. HIV and Hepatitis B), but there are also emerging infectious diseases for which it may
become necessary to test in the future (e.g. Chagas disease, and the tick-borne babesiosis
and Lyme disease).
Mosquito- borne diseases
a) On 3 March 2013 health authorities in far north Queensland admitted they were
battling four separate outbreaks of dengue fever, three in Cairns and another in Port
Douglas.. More than 80 people had been diagnosed. In the Solomon Islands, a
dengue state of emergency was declared at the national hospital on 13 March. At 15
March, New Caledonia was registering 130 new dengue cases a day.
b) Inviragen will begin the second stage of a Phase II clinical trial on its dengue vaccine.
The completion of the first stage, the company said, "determined that the first dose of
the vaccine is well tolerated in adults, adolescents and children, some of whom were
pre-exposed to dengue viruses." Dr. Gilad Gordon, Inviragen's chief medical officer
said: "The second part of this Phase II clinical trial will yield additional insight about
the vaccine's safety and immunogenicity in children as young as 18 months and will
set the stage for future vaccine efficacy studies." DENVax was developed by CDC
scientists in Fort Collins. It is designed to protect against all four strains of dengue
fever.
c) A group of French and Australian scientists say they have a promising method for
producing a live-attenuated vaccine against the Chikungunya virus12.
Influenza
d) CSIRO announced that scientists have discovered a new drug which, in the lab, is
able to prevent the spread of different strains of influenza. The drug prevents the flu
virus from removing the sugar on a cell’s surface and then binding to the cell. This
new antiviral could prove successful in modulating disease severity and slowing a
pandemic while vaccines are manufactured.
e) A Centers for Disease Control (CDC) analysis suggested this season’s flu
vaccination in the US was only 56 per cent effective for those vaccinated. Against
the A (H3N2) strain only 9 per cent of those 65 and over were protected. Most of the
elderly in the study did not receive the high-dose version developed by Sanofi to
address poor immune responses in the elderly, so there was insufficient data to see if
it performed better.
11
Cécile Courivaud, MD, of Saint Jacques Hospital in Besançon, and colleagues in the Journal of
Infectious Diseases
12
Nougairede A, De Fabritus L, Aubry F, Gould EA, Holmes EC, et al. (2013) Random Codon Reencoding Induces Stable Reduction of Replicative Fitness of Chikungunya Virus in Primate and
Mosquito Cells. PLoS Pathog 9(2): e1003172. doi:10.1371/journal.ppat.1003172
7
f)
The World Health Organization (WHO) on 21 February 2013 recommended changing
one of the three vaccine strains for the northern hemisphere's 2013-14 flu season.
Its expert group recommended staying with the A/H3N2 and A/H1N1 components,
A/California/7/2009 (H1N1)pdm09 and A/Victoria/361/2011 (H3N2). It suggested
adding B/Massachusetts/2/2012 to replace B/Wisconsin/1/2010. The new influenza
B virus is from the same Yamagata lineage as this season's vaccine. It is different
from the one the WHO's expert group recommended for the southern hemisphere In
September 2012, which included the same three strains as in the prior year.
g) For vaccine companies that plan for the next northern hemisphere season to make
quadrivalent (4-strain) vaccine that contains 2 influenza B strains, the WHO
recommends including a virus similar to Brisbane/60/2008. This was a component of
the northern hemisphere's trivalent vaccine for the 2011-12 season. It is from the
Victoria lineage. The experts’ analysis of circulating B strains found that while
Victoria lineage viruses are prevalent in some countries, the proportion of Yamagata
lineage ones continue to increase and are becoming dominant in many countries.
When they looked at patterns with the genetic clades, they found that many viruses
in clade 2, which includes B/Massachusetts/2/2012, were antigenically distinct from
those in clade 3, which includes B/Wisconsin/1/2010.
h) The H3N2 virus has been the dominant flu strain in much of the Northern
Hemisphere during the current flu season, with the H1N1 strain responsible for fewer
illnesses in North America than in other parts of the world such as Europe.
Other
i) On 6 March, the Ministry of Health in Saudi Arabia informed WHO of a new
confirmed case of infection with the novel coronavirus (NCoV). The male patient,
who died on 19 February, was aged 69. To that time, WHO had been informed of a
global total of 14 confirmed case of human infection, including 8 deaths; 7 cases,
including 5 deaths, had been reported from Saudi Arabia. There have been
suggestions that this may be a bat virus that has crossed into humans.
j) On 12 March the Ministry informed WHO of a further confirmed case, a 39 year old
male who died on 2 March.
k) On 9 March the CDC warned state and local health officials about potential infections
from the novel coronavirus, although no cases had yet been reported in the US.
l) Researchers in the Netherlands have identified the host cell protein that allows the
newly discovered coronavirus to enter its target cells, according to a study published
March 13 in Nature13.
m) On March 5, the CDC reported that bacteria resistant to antibiotics, and killing half
the people it infects has appeared in nearly 200 US hospitals and nursing homes.
The bacteria known as Carbapenem-Resistant Enterobacteriaceae (CRE) are easily
spread from patient to patient on the hands of health-care workers. CRE bacteria
can transfer their antibiotic resistance to other bacteria of the same type.
n) On 18 March, Australia’s ABC reported that Dandenong hospital had experienced
CRE but had it under control.
o) UK health officials said in February that there may be a 'superbug' gonorrhea strain
spreading across UK which is hindering treatment. There were around 21 000 new
cases in 2011, a 25 per cent increase from the previous year. The Health Protection
Agency said a third of these cases occurred in gay men. In 2012 the World Health
Organization noted that the drug-resistant strain is apparent throughout the world
13
V.S. Raj et al., “Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronvirusEMC,” Nature, 495:251-56, 2013.
8
Appendix: Alzheimer’s Disease Research
With intravenous immunoglobulin (IVIg) being trialled as a treatment for Alzheimer’s disease,
the NBA – concerned about market pressure if the trial result is positive- takes an interest in
research on other possible treatments for Alzheimer’s, on the identification of genetic
predisposition for the disease, and on improvements in diagnostic tools.
a) Researchers at the Indiana University School of Medicine have combined brain
images of people with Alzheimer’s or at risk of it with their genetic data to find a
hitherto unknown link between the gene for butyrlcholinesterase (BCHE) and betaamyloid deposition in the brain14. The study also showed that apolipoprotein-E
(APOE), a known genetic risk factor for Alzheimer’s, was also associated with the
level of amyloid found in the brain. The effect of BCHE was independent of the
APOE gene variant, but volunteers with both gene variants had more amyloid
deposition than those with a single suspect gene. The volunteers are part of the
Alzheimer’s Disease Neuroimaging Initiative (ADNI), the largest public-private
partnership to date in Alzheimer’s research. ADNI’s goal is to find neuroimaging and
other biological markers that can detect disease progression and measure the
effectiveness of potential therapies.
b) Hirano bodies are tiny. They are found in nerve cells of people suffering from
Alzheimer's, bovine spongiform encephalopathy or mad cow, and Lou Gehrig's
diseases. Researchers at the University of Georgia have now found that Hirano
bodies may play a protective role in the progression of neurodegenerative diseases
such as Alzheimer's. They have developed a transgenic mouse model that has
Hirano bodies. Says Marcus Fechheimer, professor of cellular biology: "Now we
know that Hirano bodies do not kill cells and are not toxic to mice this new model will
allow us to ask whether Hirano bodies have any effect on progression of disease in
the brain." The research was published in BMC Neuroscience.
c) Abnormal deposits in the brain thought to trigger Alzheimer’s disease can be
detected decades before the illness can be noticed, according to doctors at
Melbourne’s Austin Hospital. Their findings, published March 8 in The Lancet
Neurology, suggest there is a large window of opportunity to slow, or even reverse,
the accumulation of amyloid beta. Christopher Rowe, Austin Hospital’s director of
nuclear medicine, said “We’ve known for a long time from post-mortem studies that
apparently normal people can have amyloid in their brain, and it’s been hypothesized
that this is representing a slow build up towards Alzheimer’s disease and they just
hadn’t developed the dementia by the time that they died,” he said. “It’s very likely
that amyloid is the trigger, but the process of Alzheimer’s disease does require other
things that happen which we don’t entirely understand.” Even before dementia sets
in, shrinkage in the part of the brain linked to memory and attention occurs about four
years earlier, and memory is impaired about three years before dementia sets in.
d) A spokesman for Australian company Prana Biotechnology says of its investigational
compond PBT2 that by “targeting specific metal imbalances in the brain, PBT2
possesses the ability to ameliorate Alzheimer's pathology in relevant mouse models
for both senile plaques and neurofibrillary tangles. This data, in combination with the
previously reported Phase IIa clinical trial results for PBT2 in Alzheimer's disease
further support PBT2 as a potentially promising therapy for this devastating disease".
(Rudy Tanzi, the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard
Medical School and Prana's Chief Scientific Advisor).
14
Ramanan VK, et al. “APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir
PET genome-wide association study”. Molecular Psychiatry. Published online, Feb. 19, 2013. doi:
10.1038/mp.2013.19.
9
e) Scientists at the University of British Columbia have normalized the production of
blood vessels in the brain of mice with Alzheimer's disease by immunizing them with
amyloid beta. Recent research by the UBC team demonstrated doubling of blood
vessels in the brain of mice and humans with Alzheimer’s. Their study, led by Wilfred
Jeffries was published online in March in Scientific Reports.
f) A new drug has been developed to target a specific subtype of adrenergic receptors
(alpha-2C) in the brain, which are believed to be involved in modulation of brain
functions under stressful conditions, or the "fight or flight" response. Reporting on
the trials, author Juha Rouru, MD, of Orion Pharma in Turku, Finland was quoted as
saying. "Anytime you have a drug that targets a new pathway in the brain and shows
effectiveness in clinical trials, it is exciting." The study was discussed in American
Academy of Neurology, March 2013
10