NCT06372587: ENERGISE

Next-Generation alzheImer'S Therapeutics

Recruiting now NA Last updated 18 April 2024

What this trial tests

NA trial testing genetically encoded engineered proteins in Alzheimer Disease in 14 participants. Currently enrolling.

Timeline

19 December 2023

Primary endpoint
30 December 2024

28 February 2027

Quick facts

Lead sponsor	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Phase	NA
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	basic science
Enrollment	14
Start date	19 December 2023
Primary completion	30 December 2024
Estimated completion	28 February 2027
Sites	1 location across Italy

Drugs / interventions tested

• genetically encoded engineered proteins

Conditions studied

• Alzheimer Disease — all drugs for Alzheimer Disease →

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Who can join

Adults 18 to 80, any sex, with Alzheimer Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Is this the right time to use next-generation approaches in Alzheimer's disease (AD)? In recent years, several large clinical trials testing treatments for AD have failed, putting the entire field on a reset. AD drug trials have almost exclusively sought to use antibodies targeted toward misfolded amyloid and tau proteins. Of note, although these approaches have failed, they were designed to cover both familial and sporadic forms of AD. On the other hand, the failure in developing new effective drugs is attributed to, but not limited to, the highly heterogeneous nature of AD with multiple underlying hypotheses and multifactorial pathology. The idea underlying this project is based on the assumption that learning and memory disorders can arise when the connections between neurons do not change appropriately in response to experience. Thus, by intervening on the core mechanisms of the cellular correlate of learning and memory, i.e., synaptic plasticity, the investigators expect to preserve some of the essential brain functions in AD. By overcoming the limits of traditional AD therapeutic approaches, the investigators will use genetically encoded engineered proteins (GEEPs), which the investigators developed and tested in vitro and in murine models, to control their activity in living human neurons boosting synaptic plasticity. Indeed, outstanding and relevant progress in understanding synaptic physiology empowers the possibility to prevent or limit brain disease like never before. The investigators designed GEEPs to address some of the leading causes of synaptic plasticity failures documented in AD. Thus, GEEPs will be tested in human induced pluripotent stem cells (hiPSCs)-derived living neurons obtained from reprogrammed peripheral tissues of participants with Alzheimer's diseases. hiPSCs will be obtained from fibroblast-derived from a skin biopsy of participants with AD and controls performed in local anesthesia using a 4 mm punch. The findings will provide the first preclinical study on the effect of genetically engineered proteins to control essential pathways implicated in synaptic plasticity on AD-related cognitive decline.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.