This FOA addresses a significant need in the field: the identification of sensitive, reliable, reproducible, valid, and relevant endpoints that can be used in preclinical animal testing and human clinical trials of therapeutic compounds for IDD. One of the goals of this FOA is to align and validate outcome measures and biomarkers developed for preclinical animal testing with endpoints currently or potentially used in human trials; this FOA focuses on preclinical measures that will predict safety and efficacy of interventions in humans with developmental disabilities. Applications may also propose preclinical animal trials or replication studies conducted in a rigorous, controlled and standardized manner. This FOA is designed to stimulate and accelerate ongoing clinical and translational research in the IDDs. Potential areas of research include but are not limited to:
- Identification of sensitive, reliable, reproducible, valid, and relevant outcome measures and/or biomarkers in model organisms that address key domains of function impacted in neurodevelopmental disorders, ideally with knowledge of their neural and physiological substrates and developmental progression. Examples include cognitive function (e.g., memory, learning, executive function, attention), behavior and emotion (e.g., anxiety, aggression, and social interactions), communication, sensory impairment, auditory processing, ocular function, seizures, sleep architecture, respiratory function, endocrine regulation, and biochemical, molecular or other physiologic indices that can inform and predict outcomes in human clinical trials for IDD.
- Studies in juvenile animal models of pediatric IDD using more than one mammalian species (e.g., rodents and non-human primates) in parallel experiments in order to validate a set of measures.
- Studies of non-invasive biological and/or physiological measures of neural circuits underlying treatment response that can be evaluated in both model animals and pediatric patients.
- Investigations of biomarkers or surrogate markers of disease progression and amelioration that measure treatment response in animals and can predict outcomes in human clinical trials.
- Studies of in vivo, cellular and/or molecular measures in model organisms that are predictive of safety, efficacy, and toxicity of novel therapeutics in infants, children and adults with IDD, particularly projects that focus on neurologic, behavioral, growth and developmental outcomes in pediatric patient populations.
- Development of measures that predict specific adverse effects and toxicities of pharmacological treatments in IDD patient populations. Investigators should identify the outcomes to be assessed in preclinical studies and provide a means for determining the predictive value for the human clinical outcomes. The measures developed via this initiative may also be relevant to neurodevelopmental conditions other than the IDD syndromes listed.
- Preclinical animal trials of therapeutic compounds for IDD conducted in a rigorous, controlled and standardized manner; applications may also propose replication trials of a compound or treatment to allow an independent validation of efficacy or to address a discrepancy reported in published studies prior to launching a large scale translational project or human clinical trial.
It is important to note that biomarker discovery is rapidly advancing in other disease conditions such as epilepsy and muscular dystrophy. Thus, prospective applicants may benefit from lessons learned in other, similar endeavors. Investigators may find it beneficial to establish a multidisciplinary team that includes, for example, expertise in biochemistry, physiology, and pharmacology; behavioral and cognitive studies in animals; the design of clinical trials; clinical aspects of IDD; and other fields as appropriate.
Deadline: standard dates apply
Filed Under: Funding Opportunities