Periodic Reporting for period 1 - SEMISOFT (A web-platform interfaced software for spectroscopic molecular characterization and early diagnosis of Parkinson's disease)
Reporting period: 2022-11-01 to 2024-04-30
Everyday our life depends on a multitude of IR and Raman spectrophotometers scattered around the world even if one may ignore the importance of these instruments that are routinely employed in very important operations. A few examples are the detection of impurities in hospital respiratory gases or pollutants in the air of our cities, the analysis of blood samples, the characterization of the composition of a pigment employed in a painting to avoid its deterioration, the food and water quality check, or even forensic support to criminal investigations. The reasons why Raman spectrophotometers are preferred and their market is rapidly increasing is because these instruments are very versatile. They can equally and quickly detect gas, liquid or solid samples down to micrograms of samples. In addition, they are safe and portable, and neither destructive nor invasive with respect to the sample.
This project, called SEMISOFT, delivers a suite of codes via a user-friendly web platform to facilitate the interpretation and a better understanding of the Raman (and IR) measurements.
As a pilot test case, we pick up the challenge of the early salivary diagnosis of the Parkison’s disease (PD) from samples processed by a partner at Fondazione Don Gnocchi Research Hospital. Differently from healthy subjects, in PD patients a very important protein called α-synuclein, which is present also in our saliva, is known to undergo the formation of fibrils, a peculiar type of aggregation. Raman measurements, called spectra, are slightly different for fibrils compared to the standard protein conformation. We showed that SEMISOFT simulations are able to provide a clear indication for the early PD detection by disentangling the α-synuclein fibrils formation signal from those of many other compounds, about 2000 different types, harbored in our saliva.
Eventually, thanks to a routine salivary sampling and after some saliva sample treatments, we have been able to put forward a possible salivary test for the early diagnosis of PD.
This project, called SEMISOFT, delivers a suite of codes via a user-friendly web platform to facilitate the interpretation and a better understanding of the Raman (and IR) measurements.
As a pilot test case, we pick up the challenge of the early salivary diagnosis of the Parkison’s disease (PD) from samples processed by a partner at Fondazione Don Gnocchi Research Hospital. Differently from healthy subjects, in PD patients a very important protein called α-synuclein, which is present also in our saliva, is known to undergo the formation of fibrils, a peculiar type of aggregation. Raman measurements, called spectra, are slightly different for fibrils compared to the standard protein conformation. We showed that SEMISOFT simulations are able to provide a clear indication for the early PD detection by disentangling the α-synuclein fibrils formation signal from those of many other compounds, about 2000 different types, harbored in our saliva.
Eventually, thanks to a routine salivary sampling and after some saliva sample treatments, we have been able to put forward a possible salivary test for the early diagnosis of PD.
SEMISOFT activities have been distributed into two main steps. In the first one the goal is to achieve the creation of a web platform and employ it to suggest how to detect the presence of α-synuclein fibrils in saliva. In the second step the goal is to put forward a diagnostic protocol for the early detection of PD.
The activities of the first part involved mainly computational and theoretical chemists with the help of computer scientists for the creation of the web-platform, now available at http://semisoft.unimi.it(opens in new window). The server that hosts the web-platform is located at the host institution and the platform is a user-friendly graphical interface. Thus, no user programming experience nor desktop installation is required. The molecular dynamics (MD) α-synuclein was simulated and we generated the computational spectra for the different scenarios using the web platform. Eventually, we came up with a clear indication about the Amide I signal shape for the detection of the fibrils. Contextually, the experimental partners at Fondazione Don Gnocchi research Hospital have been trained with an ad hoc doctoral course for MD simulations and the usage of the SEMISOFT web platform. The main outcome of this part is that the web platform, which represents a prototype for commercialization of SEMISOFT, is available to the large community of Raman spectroscopy users, including both academic peers and private companies. At this regards, a marketing survey, competitive analysis, and a business model canvas have been performed during this stage of the project.
The activities of the second part focused on setting up a diagnostic protocol for the salivary detection of the PD. Indeed we are now able to discriminate with some statistical confidence between PD individuals and non-PD ones. The pool of tested people are over sixty years old ones. The main outcome of this second part is the creation of a prototype of a non-invasive diagnostic Raman spectroscopy tool for detecting new salivary fingerprints of PD.
The primary SEMISOFT stakeholders are, apart from Fondazione Don Gnocchi Hospital as described above, the PD patients, general practitioners, neurologists, and National Health Services. PD patients will benefit from an early diagnosis for the preservation of neuronal functioning, the symptom reduction, the disease progression slowdown, and the overall improved quality of life and the cost reductions. With an estimated cost of $1393 billion in 2010 and a target of 110000 patients per year, and considering about €240 billion expenses for diagnosis, the savings of an early PD diagnosis protocol are evident.
The SEMISOFT customer segments are research centers, pharmaceutical companies, and manufacturers of Raman spectrophotometers. Specifically, the global PD drugs market is projected to reach $10.4 billion by 2031.
In summary, SEMISOFT has contributed and can contribute to the advancement of clinical protocols and has the potential to generate significant social benefits in terms of early disease detection and improved healthcare outcomes.
The activities of the first part involved mainly computational and theoretical chemists with the help of computer scientists for the creation of the web-platform, now available at http://semisoft.unimi.it(opens in new window). The server that hosts the web-platform is located at the host institution and the platform is a user-friendly graphical interface. Thus, no user programming experience nor desktop installation is required. The molecular dynamics (MD) α-synuclein was simulated and we generated the computational spectra for the different scenarios using the web platform. Eventually, we came up with a clear indication about the Amide I signal shape for the detection of the fibrils. Contextually, the experimental partners at Fondazione Don Gnocchi research Hospital have been trained with an ad hoc doctoral course for MD simulations and the usage of the SEMISOFT web platform. The main outcome of this part is that the web platform, which represents a prototype for commercialization of SEMISOFT, is available to the large community of Raman spectroscopy users, including both academic peers and private companies. At this regards, a marketing survey, competitive analysis, and a business model canvas have been performed during this stage of the project.
The activities of the second part focused on setting up a diagnostic protocol for the salivary detection of the PD. Indeed we are now able to discriminate with some statistical confidence between PD individuals and non-PD ones. The pool of tested people are over sixty years old ones. The main outcome of this second part is the creation of a prototype of a non-invasive diagnostic Raman spectroscopy tool for detecting new salivary fingerprints of PD.
The primary SEMISOFT stakeholders are, apart from Fondazione Don Gnocchi Hospital as described above, the PD patients, general practitioners, neurologists, and National Health Services. PD patients will benefit from an early diagnosis for the preservation of neuronal functioning, the symptom reduction, the disease progression slowdown, and the overall improved quality of life and the cost reductions. With an estimated cost of $1393 billion in 2010 and a target of 110000 patients per year, and considering about €240 billion expenses for diagnosis, the savings of an early PD diagnosis protocol are evident.
The SEMISOFT customer segments are research centers, pharmaceutical companies, and manufacturers of Raman spectrophotometers. Specifically, the global PD drugs market is projected to reach $10.4 billion by 2031.
In summary, SEMISOFT has contributed and can contribute to the advancement of clinical protocols and has the potential to generate significant social benefits in terms of early disease detection and improved healthcare outcomes.
Raman and IR measurements are very important for molecular analysis because they can associate to each molecule a unique fingerprint. SEMISOFT is a web-platform that simulates the results of these measurements directly from standard molecular dynamics (MD) simulations. MD software are nowadays employed both by academics and in the private sector and the potential impacts of SEMISOFT are for these community that can now enhance their MD tool and interface with Raman and IR spectra.
Specifically we showed that a successful interpretation of α-synuclein Raman spectra in its different forms after suitable laboratory treatments is able to provide a diagnostic tool for the early detection of PD. This is a big step forward because a cheap salivary test may replace the current invasive cerebrospinal fluid collection and may detect the illness in the early stage when neuroprotective drugs should be more beneficial. Thanks to the SEMISOFT project, the diagnostic delay can be reduced and the disease progression can be evaluated and monitored under specific therapeutic protocols.
In the same fashion one can better understand all the Raman spectra associated to complex systems and whose spectra are now useless. For example SEMISOFT would possibly allow the identification of specific biomarkers in biological samples where now complexity is hampering a successful identification. SEMISOFT would prevent wrong or late diagnosis avoiding dramatic consequences on the individual quality of life.
In general, SEMISOFT potential users are practitioners, clinicians (neurologists), research centers. These will be interested in SEMISOFT because in a preliminary competitor analysis matrix, it conjugates early diagnosis properties with diagnostic precision. In addition, other users will be Raman spectrophotometer manufacturers, pharmaceutical companies and producers of computational chemistry software. For example, Raman producers are on the top of a growing market trajectory characterized by an estimated $71.08 billion by 2030 and a notable Compound Annual Growth Rate (CAGR) of 7.9%, placing them at the forefront of potentially exploitable opportunities and synergies. The advantages for pharmaceutical companies essentially mirror those of Raman spectroscopy. Overall we proved that SEMISOFT protocol, in aiding the early detection of PD, is cost effective.
Specifically we showed that a successful interpretation of α-synuclein Raman spectra in its different forms after suitable laboratory treatments is able to provide a diagnostic tool for the early detection of PD. This is a big step forward because a cheap salivary test may replace the current invasive cerebrospinal fluid collection and may detect the illness in the early stage when neuroprotective drugs should be more beneficial. Thanks to the SEMISOFT project, the diagnostic delay can be reduced and the disease progression can be evaluated and monitored under specific therapeutic protocols.
In the same fashion one can better understand all the Raman spectra associated to complex systems and whose spectra are now useless. For example SEMISOFT would possibly allow the identification of specific biomarkers in biological samples where now complexity is hampering a successful identification. SEMISOFT would prevent wrong or late diagnosis avoiding dramatic consequences on the individual quality of life.
In general, SEMISOFT potential users are practitioners, clinicians (neurologists), research centers. These will be interested in SEMISOFT because in a preliminary competitor analysis matrix, it conjugates early diagnosis properties with diagnostic precision. In addition, other users will be Raman spectrophotometer manufacturers, pharmaceutical companies and producers of computational chemistry software. For example, Raman producers are on the top of a growing market trajectory characterized by an estimated $71.08 billion by 2030 and a notable Compound Annual Growth Rate (CAGR) of 7.9%, placing them at the forefront of potentially exploitable opportunities and synergies. The advantages for pharmaceutical companies essentially mirror those of Raman spectroscopy. Overall we proved that SEMISOFT protocol, in aiding the early detection of PD, is cost effective.