Recent news regarding Sanofi’s decision to end its partnership with Maze Therapeutics has caused much discussion in the biotech sector, prompting this Duke AI Health Friday Roundup. We explore what this decision signifies and can take from it as we look for lessons we can glean from it.
Hebb-Williams Mazes are highly effective for controlled dry environment experiments when testing drugs or genetic modifications on spatial reference memory and hippocampal-dependent cognitive processes, as they enable scientists to track key behavioral parameters like latency, path length and errors over multiple trials to detect cognitive impairments or improvements.
The Hebb-Williams Maze
Hebb-Williams Maze (HWM) is a behavioral test designed to measure spatial learning and memory in rodents like rats and mice. Unlike other mazes that rely on environmental cues to lead animals through, Hebb-Williams maze does not use visual cues to guide animals towards an exit; animals must rely solely on problem solving abilities for navigation through. By analyzing parameters like maze latency or number of errors made during maze navigation, researchers can identify cognitive deficits or impairments while conducting longitudinal studies can assess changes over time as interventions or treatments impact cognitive function over time.
Hebb-Williams-based maze tests have historically been employed to evaluate the impact of pharmaceutical drugs and interventions on spatial cognition in both humans and animals; however, results of such studies have often been inconclusive due to an inadequacy between this paradigm and translational research validation criteria.
Criteria #1 – To fulfill this criterion, the paradigm must enable direct comparison of human and animal behaviors. In order to do so, it should also measure both how FMRP impacts behaviors as well as its biological mechanisms.
Though limited, a Hebb-Williams study is still feasible under certain experimental conditions. First, testing environments must remain uniform throughout each experiment – typically, this means using a square arena with opaque material such as Plexiglass for testing Hebb-Williams tests with starting and goal boxes located at opposite corners for each experiment and remaining there throughout its entirety.
The maze structure must also remain consistent throughout an experiment, with every arm having the same length. Furthermore, walls constructed out of similar material should ensure they are opaque and cannot be seen through. In many instances each arm may also be connected to its respective central area via an opening allowing researchers to examine each arm independently from one another.
The Morris Water Maze
The Morris Water Maze is a widely utilised behavioral test designed to assess spatial learning and memory in laboratory animals, particularly rodents. The test relies on rodents’ natural instinctive tendency to swim away from bodies of water to reach hidden platforms submerged just below its surface to escape, making this an invaluable tool in the study of Alzheimer’s, dementia, memory-related neurological conditions or any similar disorders.
MWM testing is relatively straightforward: introduce an animal into a pool of tepid water and have them swim to a floating platform, whereupon they should remain for the duration of the trial. A variety of protocols have been developed to increase its sensitivity; such as shifting platform location at each trial or placing it somewhere that normally is not visible – these cryptic changes aim to minimize external cues that the animal might use when searching for the platform, thus expanding our ability to assess hippocampal-independent navigation.
There are multiple approaches to measuring performance in the Morris Water Maze, from measuring latency to analyzing animal path strategies. Some researchers have developed automated algorithms that classify search trajectories into different search categories (Cooke et al., 2019) and this allows investigators to compare subjects against previous results and identify high-performing groups.
Researchers have acknowledged the Morris Water Maze is an effective tool for studying spatial memory, yet its drawbacks have been noted by some. Notably, certain forms of cognitive impairment in mice may go undetected by its test; moreover, animals’ visual acuity can impact MWM analyses by altering performance levels.
Researchers are actively searching for alternatives to the Morris Water Maze. Measures such as working memory, reference memory and task strategy may provide useful data, yet these assessments require complex computer software for accurate interpretation. An alternative solution would be using an electronic recording device that automatically measures animal behaviors and tracks; such automatic measurements are more precise and reliable than manual observations.
Age-Related Cognitive Deficits
Cognitive deficits pose an immense burden to both individuals and society alike. Although some cognitive decline is expected with age, more severe deficits could indicate diseases such as Alzheimer’s or Parkinson’s. By understanding their causes we may be able to halt or even reverse their progression.
Spatial behavior tasks like the Morris water maze are frequently used as measures of spatial memory formation in both rodent and human studies, providing researchers with a measure of spatial navigational memory formation.
Animals use reference cues such as landmarks to locate hidden platforms within mazes – much like how an unfamiliar environment would require navigation – and then their memory formation is assessed after multiple trials. Over time, aged rodents show a decline in performance on these mazes indicating memory decline as they age; yet its causes remain enigmatic despite extensive study by scientists studying these phenomena.
The University of Florida team’s primary aim is to use contemporary neuroscience methods to better comprehend the causes of behavioral changes associated with cognitive aging and associated diseases such as diabetes, hypertension, and heart disease. Their findings will serve as guidance for future clinical research in these fields.
UF’s research team also seeks to increase older adults’ willingness and ability to engage in cognitive rehabilitation and other clinical trial management designed to improve their well-being, maintain independence as they age, or help with cognitive training protocols prescribed by their doctors.
A study from the National Institute on Aging suggests that new technology systems may significantly increase participation. According to this research, seniors may find it easier to follow doctors’ instructions when participating in cognitive training protocols.
UF researchers have shown that cognitive exercises can delay Alzheimer’s and other neurological diseases. This research is especially noteworthy, given that most dementia cases result from neurologic conditions rather than age-related memory decline and these diseases can often be treated through medications.
Researchers who wish to understand long-term patterns must gather data over an extended period – this is what distinguishes longitudinal studies from cross-sectional ones; cross-sectionals give only a snapshot of a phenomenon at one moment in time, while longitudinal research examines correlations over time allowing more valid conclusions than with cross-sectionals alone.
Longitudinal studies can take several different forms, including cohort, panel, and record linkage studies. Cohort studies focus on sample groups with similar demographic characteristics at certain times–like birth or location–and then observe them over an extended period to see how their outcomes vary – for instance, health conditions or lifestyle choices. It is the most frequently conducted type of longitudinal research; some consider clinical trials a form of cohort research.
Panel studies are an extension of cohort studies, in which researchers observe participants at multiple points over an extended period. This type of longitudinal research allows researchers to collect both qualitative and quantitative data in either prospective or retrospective mode.
Record linkage studies use pre-existing information such as past online surveys or previous research to reveal trends that would otherwise be difficult to spot with other methods of investigation.
Longitudinal studies offer many advantages, but their implementation can be complex and time-consuming. Accumulating enough data to detect meaningful relationships may take months or years and participants often drop out at some point during their participation.
Additionally, longitudinal research can require large samples to generate accurate results; this can present difficulties when working with vulnerable or marginalized populations. Researchers must find effective means of recruiting and retaining participants, such as offering incentives or offering flexible scheduling arrangements.
Furthermore, standardized data collection procedures and recording systems that can be replicated across sites or time periods must also be established