Challenges of Neurodegenerative Diseases studies

Neurodegenerative diseases are evolving pathologies affecting the central nervous system (CNS) such as Alzheimer’s, Parkinson’s and Huntington’s diseases, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, etc.

They have been widely studied as they greatly impact our brain and motor functions such as cognition, memory, control of movement and behavior.

Hitherto, therapeutic solutions for these diseases are limited and animal models that mimic some physiological and behavioural aspect of the human diseases (sleep disorders, motor symptoms, injury, anxiety etc.) are still required.

Animal models of Neurodegenerative Diseases

Rodent models played a key role in our understanding of some of the molecular mechanism underlying neurodegenerative disease.

However, as highlighted by Weili Yang et al1, we can’t rely solely on rodent models due to genomic, molecular, and anatomic differences between rodents and humans.

Thus, the development and validation of large animal models is of primary importance to link fundamental discoveries to the clinical advances.

Following disease evolution and change in behavior

One of the issue researchers are facing when studying neurodegenerative disease is the unpredictability of the disease onset. Once the animal develops symptoms such as gait deficit, tremors, paresis, paralysis, cognitive deficit or other behavioral features, irreversible neuron destruction has already occurred.

Advances in telemetry now offers ways to assess subtle changes in neuron electrical current in EEG2, 3, 4 or behavioral phenotype4 providing leads on pre-onset phenotypes symptoms and help to target the proper therapeutic window.

This could be translated to the clinic, as McCarthy and Schueler have recently discussed the relevance of using innovative digital technology and Smart home, to digitize physiological behaviors such as sleep disturbance and gait changes to monitor and develop therapies for patients living with Alzheimer’s disease5.

Learn more about preclinical behavior applications

Measuring the impact on the cardiovascular system

Recent studies in preclinical research are showing physiological consequence reaching far beyond the CNS and sometimes in unexpected ways. These could possibly be used as additional predictive or monitoring biomarkers and following multiple measurements.

Neurodegenerative diseases have been associated with cardiovascular anomalies. For example model of Parkinson’s disease showed cardiac autonomic dysfunction, arrhythmias, conduction defects, circadian periodicity of heart rate, decreased systemic arterial pressure variation, and sudden cardiac death has been observed in some models of Parkinson’s disease2, 6, 7.

Cardiac pathology were also reported in model of Huntington’s and Alzheimer’s disease8,9.

Implanted telemetry allows short and long-term acquisition of ECG, EEG, EMG in rodents, swine, dogs, non-human primates, etc. and allow combined neuro-cardiovascular studies.

Non-invasive follow-up of respiratory system

Similarly, neurodegenerative disorders are often associated with respiratory sensitivity alteration. Those could be mild as an increase in prevalence of sleep-disordered breathing or more severe chronic restrictive respiratory insufficiency as observed in Parkinson’s model. Amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia (SCA) are progressive neuromuscular disorders that eventually lead to respiratory insufficiency10, 11.

Respiratory function can be measured by plethysmography on rodent models and have been successfully used in neurodegenerative diseases12 and could also be applied to other neurological disorders such as Neuromuscular dystrophies (Duschenne, Emery-Dreifus etc), Myopathies or Rett Syndrome.

Adding the ECG measurement combined to respiratory function is also possible using the ecgTUNNEL.

In large animals, respiratory function can be assessed non-invasively with Respiratory Inductance Plethysmography.


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