First German health insurance company reimburses proteome analysis for the early detection of diseases. ‘IK Innovationskasse’ is the first German statutory health insurance to pay for molecular early detection tests for chronic cardiovascular and kidney disease and individual carcinomas using proteome analysis. For more information, see: https://www.protexam.com/en-gb ‘IK Innovationskasse’ board member Ralf Hermes is convinced. "This form of prevention seems to have the potential to solve the cost problem in the healthcare system to a large extent," says Hermes. The ‘IK Innovationskasse’ recently began covering a large part of the costs of this new molecular diagnostic method. With the help of proteome analysis, the risk of many chronic diseases can be effectively reduced because they can be identified at a molecular level for the first time and recognised early before organ damage occurs, thus enabling efficient treatment to be initiated. It is well known that drugs only act on proteins, not on dead cells. The dilemma so far has been that chronic diseases progress without symptoms and go unrecognised in the first few years before they become noticeable with massive organ damage. They are the real cost drivers in healthcare systems because they are recognised too late and therefore have to be treated inefficiently but at great expense and in a long time. With the ageing population, the increase in chronic diseases and the retirement of significant age groups from the medical service, the problems will soon have a dramatic impact. Approximately 40% of the German population is chronically ill and therefore requires regular medical treatment. The costs for this amount to more than 120 billion euros per year. This corresponds to a third of the total expenditure of the statutory health insurance funds in Germany of just over 300 billion a year. Hermes sees it as a logical step to support this necessary paradigm shift, "away from repair medicine", with the use of proteome analysis for early detection to prevent organ damage that can no longer be stopped and is irreparable. "Better prevention through early detection also allows medical treatments and necessary medications to be better tailored to individual patients for the benefit of the health of the insured and to reduce costs more efficiently," Hermes continued. This could not only save the German healthcare system from imminent collapse, but improve patient’s quality of life and life expectancy. Newpaper articles: BILD, 03.02.2024 Berliner Zeitung, 28.02.2024

Mosaiques has informed all institutions in many contries, who are responsible for the health of the population, about the possibility of efficient management of cancer, chronic cardiovascular, and kidney diseases, the biggest problem for healthcare systems worldwide: "Efficient management of cancer, chronic cardiovascular, and kidney diseases, the biggest problem for healthcare systems worldwide, is now possible! Time to act! 80% of all healthcare costs are attributable to these diseases. Since 1989, the UN has put chronic diseases on a par with Ebola as a "threat to Western civilization". Without these underlying diseases, which are usually recognized far too late, there would be no severe Covid-19 pandemic and no other viral pandemics. In addition, environmental damage and contaminated food chains also initiate inflammation in the body, especially in the blood vessels (in the endothelium) and as a trigger for fibrosis. The demographic effects are an additional burden for Western healthcare systems and China. Further forecasts are gloomy: by 2050, the number of chronically ill people worldwide will double to 3 billion. This also applies to diabetes. For example the UAE, where more than half of the population already suffer from diabetes (~30%), hypertension, kidney and cardiovascular disease (40%), is threatened with extinction of the local population. In Germany, men already die 8 years and women 4 years earlier than in other German speaking countries (Federal Institute for Population Research). Life expectancy is also declining in the USA. Both healthcare systems are among the most expensive ones worldwide. Overtreatment, as observed for prostate cancer with 90% unnecessary biopsies and operations (ProtecT study), which has already been corrected in the USA but continues in EU countries, especially Germany, also applies to other specialist areas (angiographies in cardiology, biopsies in nephrology, ERCP in gastroenterology, etc.). A correction via legal framework or administrative interventions has only been made in the USA for prostate cancer treatment. The status quo The rigid incentive system with its favouring late treatment will exacerbate the existing underuse of early detection and treatment of chronic diseases to prevent organ damage. Incentives to improve early treatment, e.g., adjusting insulin treatment of diabetic patients in order to prevent associated diseases (CKD, CVD) have hardly been successful. At this stage, the associated diseases are already manifest, they are not recognized in time with the current diagnostics. Even the current blood pressure control with the effective drugs available is often inadequate. The necessary intensive medical monitoring of patients for individual adjustment to drugs that act on different proteins requires multiple office visits and would then still contain more conjecture than biological knowledge. The high number of heart attacks, CHD and kidney disease, the "hostage of mankind", cannot be reduced efficiently in this way. The decoded proteome solves the diagnostic dilemma and societal health problems in chronic diseases The dilemma is that chronic cardiovascular and kidney diseases can only be detected with the methods currently used (reduced eGFR and/or albuminuria) on the basis of the presence of massive organ damage. At this point, the chronic diseases progress dynamically and cannot be stopped, at best progression can be somewhat slowed. The affected organ parts are irretrievably lost and a cure is impossible. Early detection and efficient therapy require timely, highly qualified diagnostics for precise therapy determination. The disease-specific changes in the cells are controlled exclusively by proteins. Drugs only target proteins and cannot act on dead cells, as is the case with the current late detection of the diagnostic parameters used to date. Mosaiques' proteome analysis has decoded the cellular molecular level by deciphering the proteome and detecting chronic diseases such as cardiovascular and kidney diseases at an early stage, enabling timely drug intervention and preventing manifest organ damage. Various approved drugs are available to prevent the dynamic, progressive loss of organ function in these chronic diseases: Beta blockers, ACE inhibitors, sartans, statins; SGLT2 inhibitors, GLP1-RA, aldosterone antagonists, etc. The disease-specific proteome changes, for example in CKD, affect several hundred proteins. The impact varies from person to person; 150 proteins are affected in one patient, 180 in another. This impairs the effective use of medication, as each drug only acts on certain proteins. If these proteins are not involved in the disease development in an individual patient, then the particular drug cannot work in that patient! Only the proteome analysis of mosaiques can effectively predict which drugs, which all target different proteins, are best suited for an efficient timely therapy to prevent organ damage, heart attacks etc. Mosaiques’ knowledge on the proteome of also enables prediction of the development and formation of cancer already with the initial defects in the cellular signalling system. These degenerated, pre-malignant cells, which can no longer be effectively corrected by the body's endogenous mechanisms, form the basis for the development of cancer in the respective organs. Proteome analysis maps this entire molecular process of tumour onset and progression. Proteome analysis only offers tests whose clinical benefit has already been proven and approved in evidence-based studies. Development and worldwide scientific acceptance of proteome analysis Since 2002, more than 100 clinical evidence-based studies have been conducted by over 1,000 renowned physicians and scientists from cooperating university hospitals worldwide to demonstrate the benefits for each individual indication. Since 2005, over 30 studies have been funded by the EU Commission. Even then, it was obvious that genomics (which affects around 10 million patients worldwide) was generally applicable to rare diseases and proteomics to chronic diseases and their definition, specification and early detection, which affect 2 billion patients worldwide. The "MIT", the "Forum Health Research" (Helmholtz, Fraunhofer, university hospitals, and many others) name mass spectrometric proteome analysis as the key to success in efficient healthcare. More than 20 proteome-based clinical tests, most of which have emerged from EU funding, have now been approved for the early and accurate detection of a wide range of diseases. In 2016, the FDA issued a "Letter of Support" for use in the context of molecular drug testing for chronic kidney disease. The German Diabetes Society, the ERA-EDTA former presidents, the Steno Center in Copenhagen and other renowned research institutions worldwide have spoken out in favour of the early detection of chronic diseases using proteome analysis. In the meantime, meta-analyses and economic studies in Europe and the USA (e.g. Thornton Snider et al, PLoS One. 2019 May 31;14(5):e0217487 and Critelis et al, Nephrol Dial Transplant. 2018 Mar 1;33(3):441-449), all of which point to the urgency of using proteomic analysis for accurate and early detection of chronic diseases to fundamentally improve healthcare and significantly reduce the cost burden. This will maintain social peace and credibility in politics in all countries of the world. TIME TO ACT! The future of healthcare through proteomics Poking in the “haystack of uncertainty” in diagnostics and drug development has come to an end thanks to proteomic complex recognition of all proteins involved in the disease process on which drugs act alone. This revolutionary and groundbreaking aspect of mosaiques' proteome analysis, its unique selling point and the paradigm shift in individualized diagnostics and therapy, is needed worldwide. Diseases such as CVD and CKD are being defined and recognized at an early stage for the first time, so that existing drugs with their specific proteomic mechanisms of action can be used in a timely and targeted manner. Until recently, the comprehensive disease-specific proteome was not known. Drugs only targeted one or a small number of proteins and the cellular mechanism was able to re-develop the disease within a few months, using other proteins whose involvement was unknown and/or not targeted. This is the first qualified step towards personalized medicine. The scientific substance of the proteome database, which has been built up over the last 20 years with around 100,000 qualified proteomic data sets of the respective diseases, is now being used specifically for the search for qualified active substances. Deciphering the wealth of mechanisms of action of many different active ingredients from nature would take decades using conventional methods. By using artificial intelligence in combination with proteomics data, this is possible in just a few days and is already being tested in simulations on the disease-specific proteome using the database at a level of preclinical knowledge not previously thought possible. Lifestile products such as the weight loss injection in its symbiosis of lifestyle and clinical benefit (insulin stimulation) or new muscle-building active ingredients that are intended to alleviate skeletal pain through weight loss and muscle building will no longer be chance finds with the knowledge of the disease-specific proteome. mosaiques is already working with AI companies linked to major US companies. The future of personalized medicine has already begun. A central element in chronic diseases appears damage to the blood vessels (endothelium) and fibrosis and is mapped in a large number of specific proteins, the collagens. Endothelial damage and fibrosis are mutually dependent and precede chronic diseases. Only Mosaiques' proteome analysis defines and recognizes all these factors from a single sample. At the same time, this subclinical damage is the cardinal problem for triggering a pandemic in viral outbreaks. This current state of medical knowledge must be used immediately to save millions of lives; TIME to ACT !!!!"

The study about the association of air pollution with the biomarker test of biological aging was published in the Jounal Environmental Health Perspectives. This study investigated whether air pollution exposure is associated with accelerated urinary peptidomic aging, independent of calendar age and whether this association is modified by other risk factors. Among 660 participants (50.2% women; mean age: 50.7 y), higher exposure to PM10, PM2:5, BC, and NO2 was associated with a higher UPP-age-R. Studying effect modifiers showed that higher plasma levels of desphospho-uncarboxylated matrix Gla protein (dpucMGP), signifying poorer vitamin K status, steepened the slopes of UPP-age-R on the air pollutants. In further analyses among participants with dpucMGP ≥4:26 lg=L (median), an interquartile range (IQR) higher level in PM10, PM2:5, BC, and NO2 was associated with a higher UPP-age-R of 2.03 [95% confidence interval (CI): 0.60, 3.46], 2.22 (95% CI: 0.71, 3.74), 2.00 (95% CI: 0.56, 3.43), and 2.09 (95% CI: 0.77, 3.41) y, respectively. UPP-age-R was an indirect mediator of the associations of mortality with the air pollutants [multivariable-adjusted hazard ratios from 1.094 (95% CI: 1.000, 1.196) to 1.110 (95% CI: 1.007, 1.224)] in participants with a high dpucMGP, whereas no direct associations were observed. Ambient air pollution was associated with accelerated urinary peptidomics aging, and high vitamin K status showed a potential protective effect in this population. Current guidelines are insufficient to decrease the adverse health effects of airborne pollutants, including healthy aging trajectories.

Mosaiques organized an international meeting on collagen and fibrosis in Toulouse in the context of the DisCo-I project ( https://www.disco-1.eu/ ). Worldwide leading scientists, among others, Prof. Hans-Jochen Anders, Prof. Lucas Van Aelst, Prof. Anne-Dominique Lajoix, and Prof. Angel Argiles, gathered to discuss approaches towards early detection of fibrosis and prevention or even reversing this pathological development, that is the main cause for most chronic diseases (cardiovascular disease, kidney disease, liver disease, etc.). A major outcome of the meeting was the clear demonstration that fibrosis can be detected early and possible ways of therapeutic intervention, and molecular mechanisms can be unraveled using omics approaches.

The risk of diabetic kidney disease (DKD) progression is significant despite treatment with renin–angiotensin system (RAS) blocking agents. Current clinical tools cannot predict whether or not patients will respond to treatment with RAS inhibitors (RASi). We aimed to investigate whether proteome analysis could identify urinary peptides as biomarkers that could predict the response to angiotensin-converting enzyme inhibitor and angiotensin-receptor blockers treatment to avoid DKD progression. Furthermore, we investigated the comparability of the estimated glomerular filtration rate (eGFR), calculated using four different GFR equations, for DKD progression. We evaluated urine samples from a discovery cohort of 199 diabetic patients treated with RASi. DKD progression was defined based on eGFR percentage slope results between visits (∼1 year) and for the entire period (∼3 years) based on the eGFR values of each GFR equation. Urine samples were analysed using capillary electrophoresis–coupled mass spectrometry. Statistical analysis was performed between the uncontrolled (patients who did not respond to RASi treatment) and controlled kidney function groups (patients who responded to the RASi treatment). Peptides were combined in a support vector machine-based model. The area under the receiver operating characteristic curve was used to evaluate the risk prediction models in two independent validation cohorts treated with RASi. The classification of patients into uncontrolled and controlled kidney function varies depending on the GFR equation used, despite the same sample set. We identified 227 peptides showing nominal significant difference and consistent fold changes between uncontrolled and controlled patients in at least three methods of eGFR calculation. These included fragments of collagens, alpha-1-antitrypsin, antithrombin-III, CD99 antigen and uromodulin. A model based on 189 of 227 peptides (DKDp189) showed a significant prediction of non-response to the treatment/DKD progression in two independent cohorts. The DKDp189 model demonstrates potential as a predictive tool for guiding treatment with RASi in diabetic patients. LINK: https://academic.oup.com/ndt/article/39/5/873/7335297

Europe's leading physicians and biochemists - funded by the EU Commission - will meet for two days (18.-19.10.2023) in Hanover at mosaiques, the world's leading proteome company. The first meaningful proteomic definitions of the molecular development of the post-Covid-19 syndrome are expected, with the necessary differentiation from other chronic diseases. This proteome analysis test should be available to patients in the short term for targeted treatment in order to make it easier to make an exact diagnosis from only one urine sample.  The scientific consortium has already developed the molecular urine test for the early detection - within the first week - of the severe course of Covid-19 (see CRIT-CoV study ), the sub-study and approval took already place in December 2020. Despite targeted therapy options that only work in the first week, health systems have not made use of this diagnostic. Those responsible feared that patients who were not at risk would then no longer be vaccinated.

The ProSTRAT-AI international project is funded by EUREKA network and aims to improve intervention in patients with prostate cancer, by stratifying the patients to those that can continue active surveillance and which would require immediate treatment.  LINK: https://www.eurekanetwork.org/

Mosaiques Diagnostics was invited by the European Medicines Agency (EMA) to participate in a panel discussion that was held during the “Accelerating Clinical Trials in the EU” Multi-stakeholder hybrid workshop kick-off meeting on 22-23 June 2023. During the panel discussion, Mosaiques presented and discussed its proprietary model for accelerating drug development based on personalized medicine and AI approaches. Further information can be found in the following link: https://www.ema.europa.eu/en/events/act-eu-multi-stakeholder-platform-kick-workshop 

Following extensive research, the ReDiRECt project has successfully pinpointed promising drug candidates for repurposing in bladder cancer. These candidates have exhibited anti-cancer effects in pre-clinical models, and further clinical testing is planned.