The power of intelligent storage for precious brain tissues

Diseases of the central nervous system are on the rise, owing to an aging population, and a great number of studies are currently underway to help build our understanding of these complex conditions. Researching human tissue provides an accurate representation of what is happening in the human brain at a cellular, or even molecular, level. However, tissue samples are scarce, so preserving their integrity and viability is crucial to the success of research, and there is a clear need for reliable cold storage solutions that can achieve this. This article looks at the storage challenges facing researchers using tissue models, and describes how the pharmaceutical company Cerevance has overcome these difficulties to secure the future of its research programmes.

The burden of central nervous system (CNS) disorders - particularly neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis (ALS) - is increasing at an extremely concerning rate. The global incidence of ALS is expected to rise by 69% between 2015 and 2040 [1], and the number of people living with Alzheimer’s disease is set to double every 20 years, rising to 78 million by 2030 [2]. The causes of CNS disorders can vary between conditions and cases, but they are often linked to genetics, age, infections, trauma and lifestyle. The aging global population is thought to be an important factor in the increasing incidence of neurodegenerative diseases, as we live longer thanks to the successes of modern healthcare [2]. However, without a cure, patients are forced to face debilitating symptoms that can impair their quality of life and reduce their life expectancy.

Unravelling the brain’s mysteries

Many scientists are racing to find appropriate treatments that can help to slow down or even prevent the onset of various neurodegenerative diseases. However, research in this area can be incredibly challenging due to the complexity of the brain, creating several hurdles for researchers to overcome. Arguably, one of the most prominent challenges is finding appropriate models to assess pathology and aid drug development. Animal models have traditionally been used as a method for understanding the impact of CNS disorders on humans. However, the human brain is exceptionally complex, with diverse synaptic connections and neural circuit structures, and several evolutionary changes allow sophisticated functions - such as advanced language, moral reasoning and complex learning skills - that cannot be modelled in animals [3]. The poor physiological relevance of these models to the intricacies of the human brain results in them offering lower predictive power of real patient responses to treatments for CNS disorders [4]. Clinical trials for Alzheimer’s disease therapies, for example, have notoriously high failure rates, which many attribute to the premature and inappropriate translation of seemingly successful results from animal models to humans [5].

    
Brain freeze: ensuring safe sample storage

Motivated by the challenges of animal models, scientists are now implementing alternative strategies to understand disease pathologies. One approach is to create a ‘brain bank’ of human brain tissue samples, allowing primary materials to be used in biochemical studies. Working with such samples creates its own challenges, and researchers active in this area have a duty of care to ensure the integrity of these priceless biological specimens and show respect to those that have donated them. They must also adhere to stringent licensing conditions imposed by the Human Tissue Authority (HTA), including regulations for handling and storage to ensure that samples remain viable for their intended purpose.
Appropriate storage of human brain tissue samples in ultra-low temperature (ULT) freezers is essential to preserve their integrity, as even limited cycles of freeze-thawing can impact the success of biochemical studies. However, it is critical that researchers invest in systems that they can trust, as each of these samples is unique and irreplaceable. The consequences of freezer failures can be devastating, resulting in a loss of viable samples, equating to potentially millions of pounds’ worth of resources. Monitoring systems to detect any temperature fluctuations within the cold storage system are an effective way for brain banks to safeguard their specimens, providing reassurance to regulators that every reasonable step has been taken to protect their human tissue samples 24 hours a day. Efficient monitoring systems can alert users of sudden temperature spikes, giving early warnings of potential system failures and allowing efficient intervention. However, inadequate or inappropriate monitoring systems can either lack sensitivity - providing little or no warning of an impending issue - or lead to repeated false alarms, requiring unnecessary interventions, often outside of laboratory operating hours.

A no-brainer for sample security

Cerevance, based in Cambridge, UK, has curated an extensive collection of human brain tissue samples to help the company identify promising targets for the treatment of CNS disorders. With over 14,000 unique samples in its library, the company recognises the importance of efficient and effective ULT storage and monitoring. Todd Lowings, Facilities Manager and a founding member of Cerevance, explained:
“Our human tissue licence from the HTA allows us to obtain these biological specimens from libraries, and store them in -80°C freezers from Haier Biomedical for preservation. We don’t take that responsibility lightly; a lot of consideration goes into handling these samples. Part of this is to make sure that we invest in the best monitoring systems for our freezers, but it is also vital to ensure that the temperature in our lab is consistent, and assess the oxygen and carbon dioxide levels as a critical safety precaution for working with liquid nitrogen. Unfortunately, our experience with monitoring equipment in the past has been pretty poor. The biggest issue has been false alarms; we have sometimes been woken up in the middle of the night and been forced to drive into work to investigate alerts - particularly frustrating when many turned out to be errors. It has been a real headache but, of course, we have a responsibility to the donors and the company to protect the frozen samples, and had to investigate every alert to be truly confident that there was no danger.”
The research group has since acquired state-of-the-art monitoring systems from Haier Biomedical that reliably monitor data in real time, which has made a world of difference to their confidence in these instruments. Todd continued: “This system has allowed us to establish our own set-up and parameters – including setting the maximum and minimum temperature range on the probes, establishing a time delay of 15 minutes to account for the freezer being opened several times a day, and optimising the positioning of the probes - to ensure ideal working conditions. In addition, the monitors are run independently of the freezer on batteries, which means that they do not need to rely on mains electricity, and can still be used during a power outage, which is a fairly common cause of freezer faults. The batteries are also replaced annually by the supplier, giving us reassurance that the instrument will not run out of power.”
This positive experience has given the team confidence in the systems once again, and the company now has several freezers with temperature probes to house all of its tissue samples, as well as carbon monoxide, oxygen and humidity monitoring in its laboratories and offices. In doing so, the company can ensure the optimal environment for samples - from storage right through to use - avoiding unexpected variations that could result in discrepancies in research data.

Summary

Researchers at Cerevance are using a biobank of over 14,000 human brain tissue samples to identify critical targets for the next generation of treatments for CNS disorders. Preserving the company’s precious brain bank in ULT freezers is a vital step in ensuring the integrity of its tissue samples, and investing in reliable real-time monitoring systems and freezers from Haier Biomedical will help the company to secure the future of this research, offering hope to individuals affected by a range of neurodegenerative diseases.

About the authors

Scott Kerslake, IoT and Monitoring Specialist, Haier Biomedical
Scott graduated with a degree in forensics before moving into IoT-connected technologies. He joined Haier Biomedical to support the stakeholders of its IoT and monitoring portfolios, and advises customers on the best technologies for their current and future operations. He also provides ongoing technical support and training for a broad spectrum of clients from within healthcare, academia, pharmaceutical and biotech fields.

Todd Lowings, Facilities Manager, Cerevance
Todd is an industry expert with a demonstrated history of working with start-ups and well-established companies within the pharmaceutical and biotechnology industries. During the course of his career, he has accumulated a wealth of experience in facilities management, laboratory management practices, health and safety, and procurement, and has also gained a strong skillset in lab and business operations.

References

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2. Alzheimer’s Disease International. Dementia statistics. Accessed 1st September 2023. https://www.alzint.org/about/dementia-facts-figures/dementia-statistics/#:~:text=There%20are%20over%2055%20million,and%20139%20million%20in%202050.
3. Pankevich, DE., Altevogt, BM., Dunlop, J., et al. Improving and accelerating drug development for nervous system disorders. Neuron. 3, 84 (2014) 546-553. doi:10.1016/j.neuron.2014.10.007
4. Howes, O.D., Mehta, M.A. Challenges in CNS drug development and the role of imaging. Psychopharmacology 238, 1229–1230 (2021). https://doi.org/10.1007/s00213-021-05838-3
5. Drummond E, Wisniewski T. Alzheimer’s disease: experimental models and reality. Acta Neuropathol. 2, 133 (2017) 155-175. doi: 10.1007/s00401-016-1662-x. Epub 2016 Dec 26. PMID: 28025715; PMCID: PMC5253109.