The Czech-Norwegian joint project focused on discovering specific mitophagy biomarkers across Alzheimer’s Disease continuum
Assoc. Prof. Evandro F. Fang gave an excellent lecture on novel mechanisms activating ‘garbage cleaning’ (mitophagy) from the brain at the Department of Neurology, Second Faculty of Medicine in Prague. It was a great opportunity for clinicians to learn new approaches to preventing aging and AD. Also, we had some time to explore Czech cuisine and nature.
It is our pleasure to announce that Assoc. Prof. Evandro F. Fang will be a host of seminars at the Neurological Clinic of the Second Faculty of Medicine, Charles University and Motol University Hospital, with his lecture on “Cleaning the `brain garbage’ to improve cognition and quality of life in elderly”.
Ageing affects us all – come and learn more about it! The accumulation of damaged mitochondria is a hallmark of aging and Alzheimer’s disease. But did you know that the molecular mechanisms of this disruption of mitochondrial homeostasis, and their relationship to Alzheimer’s disease, are still unclear? Learn about the latest scientific hypotheses available on this mechanism. Mitophagy is a cellular self-cleaning process that removes damaged mitochondria and therefore plays a critical role in maintaining neuronal homeostasis and neuronal survival. What can lead to defective mitophagy?
Find out on Thursday, June 15th at the library of the Neurological Clinic.
The lecture is intended for the general professional public. Undergraduate and postgraduate students, and experts from the fields of medicine, natural science, and psychology are very welcomed.
This month, Czech readers can learn about healthy aging and the role of mitophagy in aging and Alzheimer’s disease prevention. In the popular Czech journal “Květy” you can find an interview with Assoc. Prof. Martin Vyhnalek, the principal investigator of MitAD grant.
On April 18 2023, researcher Evandro Fei Fang at the University of Oslo and Akershus University Hospital is the winner of the National Association for Public Health’s Dementia Research Prize for 2023.
His work in the search for effective drugs against Alzheimer’s disease is described as “groundbreaking”.
At the same time, Fang reminds that all good forces must make a joint effort to fight the disease that affects many of us.
Network for knowledge exchange
Over the past five years, Evandro Fei Fang has contributed to establishing networks for knowledge exchange between dementia researchers, held lectures about the research and his findings at prestigious universities worldwide and put the fight against dementia on the map and agenda in a number of ways.
The main reason for the award is also a concrete solution proposal Fang and his research team have put forward regarding a mechanism for removing damaged mitochondria in the brain. This track is referred to by several as “groundbreaking” in the search for effective medication against Alzheimer’s disease.
Garbage in the brain
– We believe that a main reason why we experience memory loss and other cognitive impairments when we get older is that a lot of “rubbish” accumulates in our brains over time. There is a “garbage truck” (termed “autophagy” in biology) in the brain that normally clears this away when we are younger, he says.
– When we age, however, this “garbage truck” becomes less efficient. The question is, why does this function lose effectiveness? There are several reasons, but an important element is that the garbage truck’s “engine” (termed “mitochondria” in biology) begins to wear out after many years of work. And if the engine goes on strike, the garbage truck doesn’t work well.
From theory to dementia drugs?
His hypothesis about what goes wrong when the form of dementia develops is also far more than an exciting theory. The mechanism has been replicated in studies carried out by several other research teams in a number of countries, which strengthens the belief in the potential medicinal value. This understanding of Alzheimer’s has also led to Fang and his research team identifying two promising components which they hope can be further developed into effective medicines against the disease. Evandro Fei Fang emphasizes the belief that this track can eventually lead to a better everyday life for those of us affected by Alzheimer’s.
– We should concentrate on repairing the garbage truck’s engine. The reason why we have different forms of plaque in the brain, and thus defining features of the disease picture in an Alzheimer’s diagnosis, is because this rubbish is created, but not removed. We need to add energy that restarts the engine and gets this cleaning process in the brain going again, says the award winner.
Cure requires community-wide dedication
At the same time, for Evandro Fei Fang, the fight against dementia is something that cannot be won on one’s own. He wants a joint boost against the disease, and believes we all play a key role on the road to a better future for people with dementia and their relatives.
– Our understanding of dementia and how we find the way to an effective drug against Alzheimer’s does not rest only on one lab or one research team. The whole society must work towards the same goal, not least in terms of funding. Our financial contributors, the ability to collaborate, the infrastructure around research and support from politicians and decision-makers are all very important elements. We must all play as a team if we are to manage this, he emphasizes.
The researcher is also clear about how much it means that ordinary Norwegians are on the team.
– Every kroner we receive in support moves us a small step towards the big goal. The support from private individuals through the National Association for Public Health is therefore very important to those of us who work with this every day. I hope and believe that what we are working on will be able to give a great deal of value back to society in the form of better prevention and better treatment of Alzheimer’s disease. My big thanks go to everyone who donates to the cause, says Evandro Fei Fang emphatically.
The jury’s reasoning
Since 2 October 2017, Evandro Fei Fang has been employed as a researcher at UiO, where he has established a very active group and conducts research on ageing and dementia at an internationally high level. Fang and his colleagues have put forward a new etiological hypothesis for Alzheimer’s disease – defective mitophagy, the mechanism for removing damaged mitochondria (damaged engine of the garbage truck), the cells’ energy supply. This hypothesis has been very well received in the competitive Alzheimer’s field with 676 citations to his 2017 article in Nature Neuroscience as of April this year. The proposed mechanism is supported by trials in many species and welcomed in the international trade press (among others Kingwell 2019 Nat Rev Drug Discov) and international media. An editorial in Nat Rev Drug Discov points out that increasing mitophagy is a new and promising strategy for the treatment and prevention of Alzheimer’s disease.
The studies provide immediate clinical translation since Fang has characterized several mitophagy-induced substances, e.g., the NAD+ precursor nicotinamide riboside (NR) and the naturally occurring urolithin (UA), as potential drugs against Alzheimer’s, and is now participating in clinical testing of NR in Alzheimer patients.
Very recently, the Fang laboratory has made an important new discovery: they used artificial intelligence with wet-lab validation in AD animals, and have identified two mitophagy-inducing ‘lead compounds’ as robust anti-AD drug candidates. Since 2003, over 250 drugs have been in clinical testing for Alzheimer’s, but almost all have failed. The substances have mostly only been aimed at eliminating Aβ plaques and Tau tangles. It therefore seems necessary to focus on other mechanisms.
Fang and colleagues have proposed that impaired function of the NAD+-mitophagy axis is a ‘new’ etiological mechanism for AD. Fang has shown that NAD+ treatment increases mitophagy and counteracts memory loss in 4 animal models of Alzheimer’s. This has high clinical relevance, in the short and long term: Nicotinamide riboside (NA), which is converted to NAD+ in the body, is absorbed easily after oral administration without known toxicity. Clinical trials of NR on AD patients are in progress.
Our team member, Dr. Martina Laczó, shared her knowledge and expertise at Alzheimer Cafe, an informal meeting place for caregivers, their loved ones with dementia, and professionals to share their concerns, experiences, and the joys of caring.
Dr. Laczó discussed what to do when memory problems arise, what the symptoms of dementia are, and whether there is a reliable “Alzheimer’s test”. She answered questions like: Which symptoms may indicate the disease that causes dementia syndrome? Where can I seek professional help in case of memory problems? How a comprehensive diagnosis of cognitive impairment is made. Whether it is possible to go for testing of memory and other cognitive functions as part of prevention.
Our neuropsychological team members presented the recent findings in neuropsychological research at the 39th Psychological days in Olomouc (14-16 September 2022). The neuropsychological team leader, Dr. Hana Horakova, presented her research on subjective cognitive decline „Když pacient ví, zatímco lékař ještě ne: Role subjektivních kognitivních stížností v identifikaci jedinců v riziku Alzheimerovy nemoci“ (video 1). Assoc. Prof. Tomas Nikolai talked about the need of new Uniform Data Set for diagnosis of neurocognitive impairment „Základní neuropsychologické baterie pro vyšetření neurokognitivních poruch: Tvorba a česká lokalizace“; and Veronika Matuskova, M.A. presented the concept of mild behavior impairment „Není to jen o kognici: Neuropsychiatrické příznaky v časných stádiích Alzheimerovy nemoci“ (video 2).
Assoc. Prof. Martin Vyhnalek presented the new concepts of ageing, including new information about mitophagy, during the invited lecture Cognition changes in old age: how to know we are ageing normally and how to age successfully at the 19th Seminar of practical neurology in Brno. This prestigious event for neurologists was attended by more than 250 neurologists from the Czech republic.
In November our MitAD team published a review article on Compromised autophagy and mitophagy in brain ageing and Alzheimer’s diseases in Aging Brain (an Open Access journal that complements Neurobiology of Aging).
In this review, we give an overview of autophagy and mitophagy and their link to the progression of AD. We also summarize approaches to upregulate autophagy/mitophagy. We hypothesize that age-dependent compromised autophagy/mitophagy is a cause of brain ageing and a risk factor for AD, while restoration of autophagy/mitophagy to more youthful levels could return the brain to health.
Please find the full-text here.
On the 13th of October, a satellite symposium of the Mit-AD project focused on the mechanisms and diagnosis of Alzheimer’s disease took place at the Scientific Conference of the 2nd Faculty of Medicine of Charles University. The main guests were members of the Mit-AD team Assoc. Prof. Evandro F. Fang introduced the role of mitophagy in the pathophysiology of AD, and Dr. Liu Shi, whose lecture focused on plasma biomarkers of AD. The principal investigator of Mit-AD Assoc. Prof. Martin Vyhnálek talked about new developments in the clinical diagnosis of AD, and Dr. Hana Horáková about the role of neuropsychological testing in the diagnostic process. The symposium, which included a Mediterranean breakfast, was attended by more than 60 guests from the students and staff of the 2nd Faculty of Medicine of Charles University.
With the support of EEA and Norway Grants.
