Dr Scheibye-Knudsen & The Longevity Molecule
Dr Morten Scheibye-Knudsen suspects that therapeutics to prevent age-related diseases are already on the market — we just aren’t using them in the right way. Prior to Molecule, his team had been using machine learning to analyze the medical records of 4 million Danish citizens, identifying prescription drugs associated with longer lifespans. Funding was needed to perform wet-lab testing on the possible candidates, and that’s where VitaDAO came in. By purchasing the intellectual property-NFT, this DAO, whose mission is to improve human lifespan and healthspan, was able to meet the funding goal of $250 000. Dr Scheibye-Knudsen and his team are currently testing compounds in both fruit fly and human cell models, with a reduction in cellular senescence being used as a measure of success. At the six-month review, the team had been able to rule out one compound as it had not been fruitful in the fly model. They had also identified a promising new compound that was showing consistent reduction in cellular senescence. Moreover, new avenues of research may be opened up through this study — the mechanism through which these molecules act will need to be characterized. There is still a vast library of prescription medications that could be tested, each representing a possible treatment for aging. Imagine being able to wake up and take a longevity compound cocktail each morning! Dr Scheibye-Knudsen has recently published a paper on cellular senescence, and if you look closely, you’ll be able to spot VitaDAO in the acknowledgements.
“In my core (I) believe that leveraging the community for scientific development is exciting and useful. I think we need as many minds as possible to work on these problems.”
Dr Morten Scheibye-Knudsen
Dr Korolchuk & Autophagy Activators
Aging is associated with defective autophagy pathways in cells. The process is as follows: faulty autophagy leads to an accumulation of dysfunctional mitochondria and other cellular components such as protein aggregates, which in turn cause stress pathways to be activated. These pathways deplete cellular resources to the point of eventual apoptosis, or cell suicide. One of the key reasons for defective autophagy is lysosomal dysfunction which sits right at the finish line of the autophagy process, and is Dr Viktor Korolchuk’s area of interest. Having identified possible autophagy activators, Dr Korolchuk contacted Molecule to find funding to test these activators. Within four weeks his project was assessed by VitaDAO and approved. Not only was this thrilling, but it represented the huge strides being made by Molecule to increase the ease in which projects are funded. Using Npc1 knockout cells, which are unable to form lysosomal protein and thus complete autophagy, Dr Korolchuk will administer potential activators to these cells. These compounds will also be tested against cells that lack the ability to initiate autophagy, to demonstrate the specificity of these activators to work at the terminal stage of autophagy which involves the lysosome. According to Dr Korolchuk, two of the most beneficial aspects of receiving funding through a DAO are the possibilities of collaboration and/or data sharing within the VitaDAO community.
Dr Fang & Mitophagy Activators
“A sharp body makes a sharp mind” is the sentiment of Dr Evandro Fei Fang. A trailblazer in his field, Dr Fang was the first to propose mitophagy, a subtype of autophagy, as a possible driver for Alzheimer's, and went on to demonstrate its causative role in the disease. Using AI, aptly named Fang-AI, his lab has identified compounds that may activate mitophagy. With the support of VitaDAO, other novel small molecule libraries will also be tested in Fang-AI. VitaDAO is facilitating the testing of these compounds, with Dr Fang citing the delicate nature of cell toxicity as a probable hurdle. These compounds will be tested cross-species in order to reduce the chance of false positives. If they are successful, drug therapies could be developed to treat not only patients with Alzheimer's but people suffering from all sorts of neurodegenerative diseases, such as Parkinson's, Huntington's, and ALS. Within this grant, Fang’s previous PhD student, Dr Shuqin Cao, has also received funding. During Dr Cao’s PhD, she identified two mitophagy activators in passion fruit which, amazingly, were effective at one tenth of the dose of the small molecules identified by Fang-AI. VitaDAO’s funding will allow for further structural modification to patent these molecules.
“Assigning an intellectual property agreement to VitaDAO allowed us to concentrate on the wet lab. They talk to industry to see who is willing to buy the IP, or do clinical trials. This is a win-win for both parties.”
Dr Evandro Fei Fang
Dr An & Periodontal Disease
Periodontitis, a chronic oral disease, is the inflammaging (inflammation without overt infection) of the tissues supporting our teeth. This leads to the degradation of connective tissue, bone, and eventual loss of the tooth. It is inextricably linked with aging and is not only painful, but also associated with age related diseases such as heart disease, diabetes and Alzheimer's. Dr An, a self described “dentist scientist”, is crafting the first medical non-surgical solution to this problem. This project is the first project to be funded as an IP-NFT in the US. Previously Dr An had found that the drug Rapamycin, an mTOR inhibitor, had had success in reducing age-related periodontal bone loss in mice. Based on those studies, his team will use funding from VitaDAO to test small molecule inhibitors of the mTOR pathway to combat this inflammaging. At the end of the eight week study in mouse models the aim is to see a reduction in inflammaging or even a direct improvement of periodontal disease. Although the study is examining dental disease the benefit extends further, as a prospective method to ward off many cognition- and age-related diseases. As a patient, the hope is that one day the toothpaste from your local grocery store will contain these small molecules, stopping periodontitis before it even begins.
Dr Sharma & Senolytic CAR-NK Cells
Methods to clear senescent cells have been already established, but come with the caveat of potentially deleterious off-target effects. By harnessing our own immune system, we could mitigate the damaging effect of these senescent cells, while avoiding unfortunate side effects. Dr Sharma proposed that Chimeric Antigen Receptor Natural Killer cells (CAR-NK) could be the answer, based on the success of CAR-T cells to combat cancer. Natural killer cells, our immune system’s surveillance team, are cheaper to produce and have the benefit of not needing to be derived from the individual patient, compared to T cells. Additionally, natural killer cells are cleared from the body in 2–3 weeks, which reduces the potential of off-target effects. Senescent cells have unique surface markers, three of which have been characterized by Dr Sharma’s team. VitaDAO is funding the design of natural killer cells that will recognise these markers. Dr Sharma’s research sits on the threshold of a wide range of further study; senescent cells are heterogenous, meaning that this method may not work ubiquitously. Additionally, some senescent cells are beneficial, and thus should not be a target. A resounding principle of the DeSci movement is to look at science through a different lens: one of intrigue and development rather than the pressure to report immediately actable results. VitaDAO saw the intrinsic value in this research for those reasons.
Dr Paus & Thyroid Hormones for Hair Loss
Hair loss is commonly considered a cosmetic issue but affects the majority of the population in their lifetime, and can cause great emotional distress. This is the cause that drives HairDAO, the second DAO to enter the IP-NFT arena. Leading their first project is Dr Ralf Paus, a titan in the hair loss field. Previously, Dr Paus had established that the introduction of thyroid hormones T3 and T4 was able to extend the hair follicle growth phase, stimulate keratin production, as well as mitigate hair cell apoptosis. This was done by adding thyroid hormones into organ culture, in which the hair follicles sat. Before Dr Paus, topical thyroid hormones had never been tested in the context of dermatology. Funding from HairDAO will allow Dr Paus to test T3 and T4 on human scalp skin, with a possible second bout of funding to further the research. Results are expected summertime this year. Fascinatingly, one of the drawbacks in hair loss research is model validity. Mouse hair models do not adequately emulate human hair models… so if anyone is willing to donate a bit of your scalp, let him know! A self-described luddite, Dr Paus was apprehensive of this reasonably tech savvy way of funding but guidance from HairDAO and Molecule made the process painless. He later went on to speak to one of the key advantages of being funded by a DAO: having a community of people who share your vision and can offer robust scientific commentary.
Looking to the horizon…
Hot on the heels of HairDAO is ValleyDAO. The DAO, whose focus is synthetic biology, is in talks with Dr Rodrigo Ledesma-Amaro to fund his research into lipid extraction from oleaginous yeast. While microbial lipids are far more sustainable than the alternatives; sources of animal fats and plant oils - they are more expensive to extract. Dr Ledesma-Amaro aims to combat this. AthenaDAO also has a potential IP-NFT in the pipeline, tackling ovarian aging with PhD student, Lu Dong. On the surface, female reproductive health seems to only pertain to women, but AthenaDAO reminds us that this issue matters to every person because it impacts the creation of a future generation. Outside of the umbrella of IP-NFT’s, the ever-active VitaDAO has a couple of projects on the horizon. They have funded the creation of The Longevist, a careful curation of longevity research, to be released every quarter. You can expect the first issue soon!
Experimentation is integral to scientific progression — and that extends to all aspects of the scientific process. We’d like to express our gratitude to these six researchers and their teams for embracing change and experimenting with this novel way of funding. If this resonates with you, take 15 minutes to upload your project on the Molecule website, or join our Discord.