Assoc. Prof. Evandro F. Fang with Dr. Katerina Veverova and Assoc. Prof. Martin Vyhnalek
On 18-19 September 2023, the MitAD team co-organized the 1st Norway-UK joint meeting on aging and dementia in Oslo, hosted by Evandro F. Fang (the University of Oslo and Akershus University Hospital, Norway), Lynne Cox (University of Oxford, UK) and Richard Siow (King’s College London, UK). The meeting was opened by educational and political leaders of the two nations, including Prof. Per Morten Sandset (Vice-Rector for Research and Innovation of the University of Oslo), Clare Filshie (Deputy Head of Mission from the British Embassy in Oslo), and Øystein Lund (Counsellor for Research and Education from the Royal Norwegian Embassy in London). Assoc. Prof. Vyhnalek and Dr. Veverova presented their findings from the MitAD project entitledAlterations of human CSF and serum-based mitophagy biomarkers patients from Czech Brain Aging Study (CBAS).The meeting attracted over 40 experts and scholars from 13 countries, including China, Denmark, Greece, Japan, Norway, the United Kingdom, the United States, and others. They gathered to share the latest research findings on various aspects of global ageing and to engage in discussions and workshops on topics including mechanisms of human ageing (such as genetic risk factors, DNA damage and repair, mitophagy and autophagy, etc), connections between ageing processes and disease, and promoting a healthy ageing environment. including. Importantly, discussions included potential interventions to reduce biological ageing and translation of research findings into clinical application.
Assoc. Prof. Evandro F. Fang visited the Second Faculty of Medicine, Charles University in Prague in June. During his visit, he delivered his famous lecture on novel mechanisms activating ‘garbage cleaning’ (mitophagy) from the brain at the Department of Neurology. It was an excellent opportunity for clinicians to learn new approaches to preventing aging and Alzheimer’s disease. On this occasion, he gave an interview to a hospital magazine, Motol IN, intended for patients and the general public.
You can find the issue with the article “Removing brain ‘garbage’ as a pathway to healthy brain” online here (Motol IN č.7-8/2023).
Here we provide the original version in English:
You recently received an award for your excellent dementia research (National Association for Public Health’s Dementia Research Prize for 2023). What does such an award mean to you and your team?
EFF: It was such a big honour as a laureate of the National Association for Public Health’s Dementia Research Prize for 2023 presented by H.M. King Harald V of Norway. This is among the most prestigious awards in the science fields in the Scandinavian countries, and is to give recognition to researchers or clinicians who have contributed significantly to the understanding or treatment of dementia. Such a big award to a young research, it really encourages me to work harder on the way to find a cure for Alzheimer’s disease, the most common dementia worldwide.
What is the best way to improve human mitochondrial function? Can we change anything in our lifestyle?
EFF: Mitochondria are the powerhouses of our body and mitochondria are dynamic (fusion and fission) and fragile. It has been reported in both laboratory and clinical studies that interventions like exercise and healthy diet can improve mitochondrial numbers and quality. Exercise and healthy diets are public accessible approaches to work with.
You have been working as a researcher in the US and in Norway. How do the conditions for scientists in the two countries differ?
EFF: I have been working in Hong Kong (4 years), Baltimore in the USA (6 years), and Oslo (Norway, almost 6 years). I have had great and positive experiences in studying and living in these charming cities. Speaking of science they are different: the working speed is Hong Kong is very fast and professional; in the USA, the research competitive is very high and among the highest quality; in Norway, the funding is very decent and the research environment is open and thus one can have a great balance of life and scientific career.
What would you advise young researchers to succeed in their careers?
EFF: To set up a goal of your career, and based on this goal to develop your training plans and to rich your CV. Definitely, in such a world with international competition in most scientific jobs, we need to work hard in a happy way. A key to make us happy is to choose the career that one really love.
In your opinion, what is the most pressing research question that needs to be addressed in the field of mitophagy and Alzheimer’s disease?
EFF: Our 2019 paper on Nature Neuroscience is considered a milestone on targeting defective mitophagy as a druggable target for Alzheimer (with more than 800 citations since 2019). Since then great efforts by many other labs and us have done on the mechanistic studies of defective mitophagy in Alzheimer as well as on the development of novel drug candidates for Alzheimer. Some novel mitophagy-inducing molecules show great anti-Alzheimer activity in laboratory models and human iPSC-derived cellular systems; furthermore, these molecules are bioavailability, with favoured pharmacokinetics, and some can pass the blood-brain barrier. Thus, the most pressing question is to test them in clinical trials for Alzheimer.
Can you tell us your assumption when will be possible to treat Alzheimer’s disease causally?
EFF: Alzheimer’s is likely a group of diseases which make it challenging to find a drug to cure all individuals with Alzheimer’s. The exciting news on the 25-35% efficacy in reducing memory loss of newly developed anti-Abeta antibodies bring us hope. Targeting on offsetting defective mitophagy may show a more profound benefit as it could reduce many risks/causes of Alzheimer’s (Nature Review Drug Discovery Turning up mitophagy in Alzheimer disease – PubMed (nih.gov))
Welcome to join us the 1st Norway-UK meeting on ageing and dementia on 18-19 Sep. 2023!
We are pleased to invite you to this exciting meeting, where scientists from the most prestigious universities will share their research on aging and dementia. Assoc. Prof. Evandro F. Fang is an organizer of this event, where Assoc. Prof. Martin Vyhnalek and Dr. Katerina Veverova will present the results of the MitAD project on mitophagy biomarkers in the AD continuum.
Our team had the great opportunity to present our preliminary results of the MitAD project at AAIC 2023 in Amsterdam. We enjoyed talking to researchers from all over the world and sharing our exciting discoveries on mitophagy across the Alzheimer’s disease continuum. Just like we enjoyed the informal time with the whole Czech Brain Aging Study (CBAS) team.
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 Medicinein 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.
Assoc. Prof. Martin Vyhnalek was a host on the popular Czech TV show “Fokus VM” with the theme of a LONG LIFE, where he discussed the importance of healthy mitochondria in successful aging.
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.
The king together with the laureates of this year’s research awards: Dan Atar (middle) for research on cardiovascular disease and Evandro Fei Fang (left) for research on dementia. Photo: Nasjonalforeningen for folkehelsen
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.
Evandro Fei Fang and his team from Norway
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.
