How does NeuroScience Associates support amyotrophic lateral sclerosis (ALS) research?
We are a specialty CRO that works with scientists across a broad spectrum of research, some of which is focused on ALS. We utilize our expertise in study design, histology, and pathologic analysis to provide our clients with high throughput services. Beyond our business activities of processing our clients’ tissues, we have a special interest in ALS. We are blessed with directed donations of brain and spinal cord tissues from two ALS heroes. We’ve initiated an expansive histologic evaluation of the first brain as proof of concept of how researchers can thoroughly and efficiently investigate the entire brain histologically.
What are some key achievements?
Many years ago we developed Large Format™ sectioning and staining capabilities, which enable us to section an entire, intact human brain hemisphere. Rodent models are an important part of CNS research, but there is no substitute for investigating the pathology in actual human brains.
In 2018 we began high throughput whole slide scanning with the acquisition of our first state of the art system. We’ve since purchased additional systems to accommodate rapidly increasing demands for not only brightfield but also fluorescent markers. The systems quickly digitize our standard 2×3” MultiBrain® slides, each of which displays stained sections from up to 42 tissues. Even more impressive, they digitize 3×5” ALS human brain tissue with relative ease.
Acquiring images is great, but opening access to them via an image sharing platform that allows our clients and other researchers to explore these massive whole slide images, was the next big task. Through our use of the Proscia platform we can now provide such access.
The biggest achievement of all is underway. Thanks to Aiforia and their AI algorithms, the images are being converted to masses of data. The translation of the ~petabyte of data (for each brain!) to searchable and useful information, we expect will unveil unexpected and exciting new truths about ALS that will provide researchers with extraordinary new targets.
What do you believe are some of the most important unsolved questions in ALS research today?
Determining the etiology of the disease is the most important thing to sort out. Some genetic/hereditary markers have been found in some patients, but not all. What other factors contribute to the onset and progression of ALS?
A lot of attention is given to lower motor neurons in the spine for obvious reasons, but I think the relationship and connection to upper motor neurons in the brain should be explored more. What is happening in motor cortex early on before clinical symptoms arise? What antibodies can be used in IHC applications to study upper motor neurons? What role are glia playing in the disease progression?
Why is it important to continue to raise awareness?
ALS is a particularly devastating CNS disease with an imminent death sentence and no treatments that significantly extend the 2-5 year survival post diagnosis. There are approximately 16,000 people in the US living with ALS. While that may seem relatively small compared to other CNS diseases like AD and PD, every 90 minutes another ALS patient in the US loses their battle.
The benefits of this focused ALS research will be far reaching as all CNS research is important in developing our understanding of how the brain functions. Serendipitous discoveries in one field of study often lead to advances in other fields.
How do you think the research project with Aiforia will help advance ALS research?
Digitizing the stained human brain hemispheres is essential for compiling useful data. However, analyzing images of that number and size is daunting to say the least. Combining the Large Format™ neurohistology and digital imaging expertise of NSA Labs® with Aiforia’s artificial intelligence platform creates a powerful toolbox for extracting data from ALS brain and spinal cord tissues. Instead of simply sharpshooting areas of known pathology, a thorough representative set of sections throughout the brain and the spinal cord, covering numerous traditional and antibody stains, will be analyzed, leaving no stone unturned in hopes of elucidating previously unknown patterns and mechanisms associated with ALS. NSA’s Large Format™ tissue processing and whole slide imaging provides an exceptional foundation to which Aiforia can apply powerful, custom built AI algorithms for data extraction.
Bottom line impact? I’m optimistic that this initial proof of concept will yield such exciting data that it will lead to the funding of an expansive project. Hundreds of ALS brains and spinal cords will be thoroughly analyzed and we will shorten the time to a cure by decades!
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