Revolutionary Nasal Spray Drug Offers Hope for Alzheimer’s Treatment – New Research Uncovered

Researchers at Università Cattolica and Fondazione Policlinico Universitario A. Gemelli IRCCS have made a significant finding in the treatment of Alzheimer’s disease. They found that a nasal spray drug can inhibit the brain enzyme S-acyltransferase (zDHHC). This inhibition may help reduce cognitive decline and brain damage associated with Alzheimer’s.

In their study, led by Professors Claudio Grassi and Salvatore Fusco with the University of Catania’s collaboration, researchers noted that the brains of Alzheimer’s patients contained high levels of S-acyltransferase. This enzyme could be a target for new drugs. Furthermore, they discovered that more of this enzyme was linked to poorer cognitive performance. A grant of €890,000 from the Ministry of Health will support the exploration of new therapies targeting this enzyme.

Alzheimer’s disease involves changes in proteins like beta-amyloid and tau, leading to their aggregation in the brain. These proteins’ functions are influenced by chemical modifications, notably S-palmitoylation, facilitated by S-acyltransferase enzymes. Previous studies indicated that abnormal S-palmitoylation affects cognitive abilities in metabolic diseases, including type 2 diabetes, which is often associated with Alzheimer’s.

In this study, the researchers found that early Alzheimer’s symptoms resemble brain insulin resistance, increasing levels of the zDHHC7 enzyme and altering the S-palmitoylation of proteins essential for cognitive functions.

In animal models, inhibiting S-palmitoylation minimized harmful protein accumulation in neurons and slowed cognitive decline. In post-mortem brains of Alzheimer’s patients, higher levels of zDHHC7 correlated with reduced cognitive performance. Experimental nasal spray “2-bromopalmitate” effectively stopped neurodegeneration and extended mouse lifespans.

Currently, no drugs selectively block zDHHC7, and 2-bromopalmitate lacks precision. However, with 2023 PNRR funding, researchers will test new approaches, such as “genetic patches” that target zDHHC7 RNA or engineered proteins that disrupt its activity.

This research offers hope for future Alzheimer’s treatments through a better understanding and targeting of the zDHHC enzyme.

Reference: Natale F, Fusco S, Grassi C. Inhibition of zDHHC7-driven protein S-palmitoylation prevents cognitive deficits in an experimental model of Alzheimer’s disease. PNAS, 2024.