MASSACHUSETTS GENERAL HOSPITAL — Department of Health and Human Services STTR Phase I: NIA

Description

Abstract Overmillion Americans are currently affected by Alzheimerandapos s diseaseADwith an economic burden estimated at andgt$billion year inthat is projected increase at least four fold over next several decadesIn spite of the dearth of pharmacological options to modify the course of the disease at presentthe field has developed accurate biomarkers that demonstrate that the pathology of AD is presentyears of more prior to the onset of memory symptomsThere is converging opinion at the national level and within pharmaceutical companies that our best strategy to develop disease modifying therapies is to design clinical trials during this asympomaticpreclinical periodThe accurate biomarkers that detect individuals in theyear preclinical period of ADprior to the onset of memory symptomshave limitationsThey are largely radiological indicatorswhich are expensive and require the subject to travel to a remote locationMoreoverwith the advent of a disease modifying therapeuticscreening themillion people above the age ofto determine who would benefit from this therapy is prohibitively expensiveTo address this critical unmet medical needwe developed an algorithm of olfactory tests that functionally probe two vulnerable neural circuits with early signs of pathologyolfactory and memory circuitsIn clinically normal elderly individualswho have undergone longitudinal neuropsychological testing and radiographic phenotypingthe Percepts of Odor Episodic MemoryPOEMalgorithm identified clinical normal individuals with selective odor memory deficitsnormalized to other aspects of their individual olfactory functionodor discrimination and odor identificationThose clinically normal elderly individuals with a selective odor memory deficit were enriched in thekey AD risk factorsApoEthe strongest genetic risk factor for ADevidence of neurodegeneration in a key memory and olfactory processing area of the brainandmost importantlya significant decline in cognitive function over timeIn order to fully explore the potential of this findinghere we seek to expand our participant pool by creating a digital olfactory battery that couples with the POEM algorithmwith the ultimate goal that this can be self administered independently at homeTo accomplish this goalwe have partnered with a leading digital health companythe ADK groupto develop a mobile app and Scentovationsa company taking an innovative approach to the design and manufacturing of odor delivery devices that are either reusable or disposableThe mobile app will organize the subjectandapos s experience with instructions and cueswill collect the response data generated in response to the testsand will send it securely to a central locationIn additionproprietary naturalistic odors developed by International Flavors and Fragrances will be incorporated into this battery to improve the perceptual salience of odors and performance across different cultures and continentsFollowing the development of this prototypewe will seek to validate it in both a clinical and home settingUsed alone or together with other non invasive measures that probe function of different brain regionsa remote test to identify cognitively normal people harboring AD pathology and at risk of developing clinical AD is an essential step to developing and clinically managing therapies that will impact the growing epidemic of AD Project Narrative Detecting clinically normal elderly individuals with AD pathology and following their disease progression in a non invasiveaffordable manner is a critical step to developing and monitoring disease modifying therapiesWe developed the POEMPercepts of Odor Episodic Memoryalgorithm to identify cognitively healthy elderly individuals with neurodegeneration in their memory circuits and significant cognitive decline over timeTo seek further validation of this promising methodologywe have teamed with a leading digital health company and propose to develop a digital olfactory battery for remote assessment of the POEM algorithm using novel odor diffusers and naturalistic odors