|Toxoplasma gondii parasite up close. Credit: University of Melbourne|
In the July 14 edition of Scientific Reports, 39 researchers from 14 leading institutions in the United States, United Kingdom and France suggest novel approaches that could hasten the development of better medications for people suffering from toxoplasmosis. This chronic, currently incurable infection, caused by the parasite Toxoplasma gondii, infects the brain and eye of as many as 2 billion people worldwide.
Their findings provide conceptual and practical roadmaps for improving the efficacy and reducing toxicity of available medicines. They also offer insights into the biology of T. gondii, suggest critical molecular targets for new medicines, and offer renewed hope for the speedy development of much-needed curative medicines for those with toxoplasmosis—and potentially malaria.
The researchers describe three significant steps forward:
The team's findings matter because T. gondii is the most frequent cause of infection leading to destruction of the back of the eye for persons in most countries in the world. It is most damaging for infants and children who acquire infection from their mothers during gestation, but it can also cause life-threatening infections in those with compromised immune systems, such as those with cancer, autoimmune disease or AIDS. Highly virulent strains of Toxoplasma are also now known to cause lethal disease, especially in South America.
A large data analysis by researchers at the University of Chicago, published June 26, 2016, in Clinical Infectious Diseases, found that the estimated annual incidence of toxoplasmosis over the last ten years in the US was 6,137 people, based on diagnostic codes for the disease. An editorial in that journal notes that these data "are the strongest to date to indicate that toxoplasmosis represents a significant disease burden in the United States."
More information: Martin McPhillie et al, New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections, Scientific Reports (2016). DOI: 10.1038/srep29179
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I copy news articles pertaining to research, news and information for Parkinson's disease, Dementia, the Brain, Depression and Parkinson's with Dystonia. I also post about Fundraising for Parkinson's disease and events. I try to be up-to-date as possible. I have Parkinson's diseases as well and thought it would be nice to have a place where updated news is in one place. That is why I began this blog.
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|Dr Nikolai Petrovsky and a 3D protein model being used in the development of a possible Alzheimer’s disease vaccine. Credit: Flinders University|
With more than 7.5 million new cases of Alzheimer's disease a year, the race to find a vaccine and effective treatment for dementia is growing by the day.
Now, researchers in the U.S. and Australia have made a breakthrough discovery in the international quest to discover a new and potentially effective vaccine targeting the pathological proteins associated with Alzheimer's disease (AD), the most common cause of dementia in the elderly.
In research findings just released in Nature's Scientific Reports journal, Flinders University experts, as part of a high-level U.S. research team at the Institute of Molecular Medicine (IMM) and University of California, Irvine (UCI), have made a successful vaccine formulation that targets the abnormal beta-amyloid and tau proteins that signal Alzheimer's disease.
With more than 48 million dementia cases in 2015, Alzheimer's is emerging as one of the costliest to the world's health care systems, especially in mature economies in Western countries.
The World Health Organisation has projected the total global societal cost of dementia-related illnesses and care at more than $US600 billion a year.
"If we are successful in pre-clinical trials, in three to five years, we could be well on the way to one of the most important developments in recent medical history," says Flinders University School of Medicine Professor Nikolai Petrovsky, director of South Australian vaccine research company Vaxine Pty Ltd.
"Along with our rapidly aging populations, we now know that the explosion in type 2 diabetes in the West is likely to further dramatically fuel the projected rise in the number of cases of dementia globally, with diabetes being the major risk factor for Alzheimer's disease," Professor Petrovsky says.
The scale of the dementia problem has seen the U.S. Congress commit a further $US350 million to the National Institutes of Health (NIH) for research into Alzheimer's disease, taking research funding in the US to more than $US1.3 billion this year.
With NIH and Alzheimer's Association funding, the U.S. researchers say they have developed an "exceptional" universal vaccine platform, called MultiTEP, to target the hallmark proteins, aberrant forms of AB and tau proteins.
β-amyloid (AB) is a protein found to be prominent in driving Alzheimer's disease, but the accumulation of pathological tau also correlates with the formation of dementia in Alzheimer's patients.
Using a combination of anti-amyloid-beta and anti-tau vaccines with powerful and safe adjuvant technology called Advax developed by Vaxine Pty Ltd "shows promise for both preventive and therapeutic approaches in AD," Professor David Cribbs told Bloomberg news agency in the U.S.
Professor Michael Agadjanyan, head of IMM Department of Molecular Immunology, says the MultiTEP platform-based vaccines "do not induce potentially harmful auto-reactive cellular immune responses, while still generating antibodies that bind strongly to the amyloid and tau pathological molecules in brain tissue from AD patients."
Co-author of the latest paper, IMM Department of Molecular Immunology, Associate Professor Anahit Ghochikyan, says, "This study suggests that we can immunise patients at the early stages of AD, or even healthy people at risk for AD, using our anti-amyloid-beta vaccine, and, if the disease progresses, then vaccinate with another anti-tau vaccine to increase effectiveness."
She says the cooperative studies with National Institute of Aging IMM scientists and collaborators from UCI and the University of Southern California are working with experts from four companies to conduct non-clinical safety-toxicology studies to fulfil US Government safety standards for the Investigational New Drug application.
After completion of these pre-clinical studies, they plan to test the immunogenicity and efficacy of the new vaccines in human trials.
Cutting-edge research company Vaxine Pty Ltd is internationally renowned for developing the world's first swine flu vaccine during the 2009 pandemic and is active on other fronts including Ebola and Zika virus research.
The vaxine is funded by the U.S. NIH to develop novel compounds called adjuvants that play a critical role in maximising vaccine effectiveness. The Vaxine Advax adjuvant technology is a key component in the development of IMM's Alzheimer's vaccine.
More information: Hayk Davtyan et al. Alzheimer's disease AdvaxCpG- adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules, Scientific Reports (2016). DOI: 10.1038/srep28912
July 15, 2016
WEST LAFAYETTE -
The National Institute of Environmental Health Sciences has awarded a five-year, nearly $1.7 million grant to a Purdue University health sciences professor. Jason Cannon will use the funds to determine if dietary factors have a role in Parkinson's Disease.
Cannon is an associate professor of toxicology in Purdue's School of Health Sciences. The study seeks to determine if heterocyclic aromatic animes, a possible carcinogen that is formed when grilling meat at high temperatures, is also a neurotoxin linked to the disease.
"Other researchers have found that the class of compounds heterocyclic aromatic animes are probable carcinogens, and one of these cancer scientists shared with me that while the animals in their study were exposed to the carcinogen, they also experienced neurological problems," said Cannon. "My lab's work has found that when we isolate neurons in cultures and expose cells to reasonable doses of these compounds, yes, we see the same types of neurons lost in Parkinson's disease."
Purdue says Cannon will study the compound's effect more in-depth. Cannon says he is interested in looking at factors that cause Parkinson's which people could potentially encounter every day.
The study is being done in collaboration with other researchers from Purdue, as well as researchers from the University of Minnesota, the Defense Threat Reduction Agency in Virginia and the Biosciences and Biotechnology Division at Lawrence Livermore National Laboratory in California.
Most common was non-amnestic with executive dysfunction
In the observational LANDSCAPE study, the most common subtype of PD-MCI was non-amnestic single domain (39.4%), Elke Kalbe, MD, of University Hospital Cologne in Germany, and colleagues reported online in the Journal of Neurology, Neurosurgery and Psychiatry.
They also found that age, gender, and global cognition predicted disease subtype -- and they noted that additional longitudinal research is needed to determine whether these specific MCI profiles predict the development of dementia in Parkinson's patients.
About a quarter of patients with Parkinson's have MCI, and higher rates have been reported with more advanced disease severity. Some work has suggested that PD-MCI also predicts conversion to dementia.
Researchers also believe the MCI seen in Parkinson's is different from that involved in Alzheimer's disease: it appears to affect executive function rather than memory.
However, the jury is still out on PD-MCI, as results regarding the cognitive profile of patients with Parkinson's have been variable and have come from small studies. Indeed, the Movement Disorders Society's most recent (2012) guidelines on diagnosing MCI in patients with Parkinson's caution that its criteria will require validation and will likely be refined with additional research.
To further clarify the issue, Kalbe and colleagues conducted the LANDSCAPE Study, a multicenter, prospective observational trial of 269 patients with PD-MCI -- the largest number of prospectively recruited patients with PD-MCI to date, the researchers said.
About two-thirds of patients with PD-MCI had executive impairment (65.3%), followed by visuospatial (36.3%), memory (33.5%), attention (25.8%), and language impairment (6.5%).
After non-amnestic single domain MCI, the largest subtypes of participants were amnestic multiple domain (30.5%), non-amnestic multiple domain (23.4%), and amnestic single domain (6.7%).
The tests most frequently impaired were the Modified Card Scoring Test (MCST) (number of categories 43.5%), the digit span backwards (36.1%), and the word list direct recall (31.2%).
Regression analyses showed that lower global cognition, female gender, and higher age predicted PD-MCI subtypes -- but education and disease-related parameters did not.
"Our finding that executive dysfunctions are the most typical cognitive symptom in PD-MCI is in line with recent reviews and original studies and reflects the fact that the 'cognitive' frontostriatal loop projecting from the dorsal striatum to the dorsolateral prefrontal cortex, which is related to executive functions, is affected early in patients with PD," the researchers wrote. "Likewise, executive dysfunctions are most typical in newly diagnosed, drug-naïve patients with PD."
Kalbe and co-authors did acknowledge, however, that some studies have shown memory to be most frequently impacted in Parkinson's, and this could be due to methodological differences in studies, or it may reflect different neuropathological pathways that suggest different subtypes of Parkinson's disease.
The team also noted that patients with the amnestic multiple domains subtype had the lowest performance in global cognitive scores, suggesting that these patients may be the most likely to go on to develop dementia.
"Predicting the [amnestic multiple domains PD-MCI subtype] with variables that are easily available in clinical routine could be useful, as this subtype scored lowest on global cognition and ... may thus be 'closest' to dementia." The researchers cautioned, however, that commonly used cognitive tests vary greatly in their sensitivity to detect dysfunction.
The study was limited because PD-MCI diagnosis was not based on the Movement Disorders Society criteria since those were not available when the study started, and because the small size of the amnestic single domain subtype may have confounded statistical comparisons between this and other subtypes.
Kalbe et al concluded that additional longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks for developing dementia.
The study was supported by Novartis, the International Parkinson Fonds, and the German Ministry for Education and Research.