Early, non-invasive diagnosis of neurodegenerative disease will be a game changer
Structure is often related to function, and that is frequently the case with proteins which exhibit several levels of complex structural organisation. Misfolded proteins are typically inactive. However, in some cases, these unstable proteins or pieces of them (peptides) can aggregate into stable assemblies that interfere with cell function. With the support of a Marie Skłodowska-Curie Actions Individual Fellowship(opens in new window) for the UPRECON project, Piotr Hańczyc of the University of Warsaw(opens in new window) has developed a technology that detects the early stages of such aggregation, indicative of neurodegeneration, before clinical symptoms appear. This opens the door to more effective therapies that slow or halt the progression of neurodegenerative diseases, enhancing the quality and potentially duration of life for millions.
Sticking together through thick and thin
Some of the most important protein-misfolding diseases are associated with amyloid aggregates(opens in new window). Amyloid aggregation begins with the clustering of several misfolded protein or peptide monomers to form oligomers(opens in new window). These, in turn, can self-organise into cytotoxic and stable polymeric fibril-like assemblies rich in beta sheet(opens in new window) regions called plaques. Formation of an amyloid state of proteins is associated with numerous diseases(opens in new window), including Alzheimer’s, Parkinson’s and Huntington’s disease, as well as type 2 diabetes. Increasing life spans and changing lifestyles will likely increase the incidence of these conditions with ageing. Enhanced diagnosis and treatment will not only benefit the millions of patients globally but also reduce the financial burden on patients, their families and healthcare systems.
Two photons are better than one
While technology and understanding have advanced tremendously, until now scientists could only detect mature amyloid fibrils usually associated with advanced disease stage. Hańczyc has overcome this barrier using ultrafast laser spectroscopy in combination with two-photon excitation with near-infrared light(opens in new window). It induces strong light absorption by amyloids but not natural proteins. Hańczyc expands: “I found that the amyloid aggregates in the early stages of formation exhibit a unique optical signal that differentiates them from more mature aggregates.” Given that near-infrared light can penetrate deep tissue and its absorption does not damage cells, it could become a method of choice for brain scan tomography and early detection of protein aggregation.
Early diagnostics of neurodegenerative disease
Hańczyc built on his discovery to develop a patented methodology leading to the creation of a spin-off company. “The technology enables the detection of oligomeric forms of amyloid fibrils from the very early stage of their aggregation in cerebrospinal fluid from patients with Alzheimer’s disease,” he says. His company will validate the technology with a larger sample from volunteers who could develop cognitive symptoms in 10 to 15 years. The MSCA grants are very competitive, funding projects with a high level of risk but a tremendous potential if successful. Hańczyc has delivered on that potential and with this launched his career dedicated to developing safe and non-invasive optics-based tools for neurodegeneration. “Thanks to better understanding of the molecular mechanisms underlying neurodegeneration, we can develop new techniques capable of detecting, treating and eliminating the risk factors. These powerful new tools will enable personalised diagnostics and therapies,” Hańczyc concludes.
Keywords
UPRECON, protein, amyloid, aggregates, neurodegeneration, fibrils, Alzheimer’s, near-infrared, spectroscopy, two-photon
