November 25, 2024

expert reaction to study in mice testing nasal treatment for Alzheimer’s disease

A study published in PNAS looks at a nasal treatment for Alzheimer’s disease in mice. 

Dr Richard Oakley, Associate Director of Research and Innovation, Alzheimer’s Society, said:

“We know that many different proteins such as amyloid build up in the brains of people with Alzheimer’s disease and cause damage to brain cells, however, understanding how and why damage is caused is still being explored by researchers. The importance of amyloid was highlighted in 1989, when Alzheimer’s Society funded research led by Professor Sir John Hardy helped us understand the role of the amyloid protein in Alzheimer’s disease. 

“This recent study focuses on an enzyme in the brain which makes changes to many different proteins such as amyloid. It was found that using a drug which ‘switches off’ the enzyme could reduce the damage to brain cells by lowering the amount of protein building up. This highlights a potential avenue for future treatment of early-stage Alzheimer’s disease, targeting this enzyme. 

“This is incredibly early stage research and more investigation would be needed to understand if this nasal spray drug could be used in humans, but it is exciting to see another possible treatment being developed for this highly complex disease. 

“Many treatments we are seeing developed today are most effective in the early stages of dementia. It’s critical we improve diagnosis so that people are diagnosed earlier and can access treatments available today and the treatments of the future.”

Dr Julia Dudley, Head of Research at Alzheimer’s Research UK, said:

“It is encouraging to see research like this. We urgently need more effective and affordable treatments for people living with dementia. Not only this, but they also need to be quick and easy to deliver.

“Researchers looked at a protein in the brain called ‘S-acyltransferase’, which has been linked to cognitive decline in Alzheimer’s disease. By targeting this protein with a nasal spray they found that they could slow down memory problems in mice.

“However, there is still a long way to go. It’s important to note that as these findings were in mice, researchers will need to test this treatment in clinical trials before we know whether this is effective for people living with dementia.

“Alzheimer’s Research UK are committed to finding new treatment options that could bring us a step closer towards a cure.”

The following comments were provided by our friends at the Spanish SMC:

Eloy Rodríguez, neurologist at the Marqués de Valdecilla-IDIVAL University Hospital and lecturer at the University of Cantabria, said:

“It seems to me an interesting article, of high scientific level and very well done, which opens the way to a new therapeutic target in Alzheimer’s disease. Its main limitation is that it is still a study carried out in mice (although there is a part in which they use post mortem tissue from Alzheimer’s patients, the ‘therapeutic’ part is done in transgenic mice).

“The fact that it works in transgenic mice, used as Alzheimer’s models, is far from being equivalent to a potential efficacy in humans, but it is an avenue that will be worth exploring further in successive studies.”

Xavier Morató, director of Clinical Trials at Ace Alzheimer Center Barcelona, said: 

“There is an urgent need to find molecules that target the initial and early events of the Alzheimer’s disease cascade. Oral and subcutaneous GLP1 agonists are currently in phase III evaluation for the treatment of the disease and have been shown to improve insulin sensitivity and reduce inflammation.

“In this work, we observed increased total protein palmitoylation pattern levels and expression of several enzymes called zDHHC in the hippocampus of transgenic mice at an early stage of the disease and in the human brain with Alzheimer’s disease.

“Altered brain insulin signaling led to epigenetic regulation of zDHHC7 in a mouse model of cognitive impairment. This work uses an intranasal inhibitor of zDHHC7, providing a noninvasive route of administration to reach the central nervous system.”

‘Inhibition of zDHHC7-driven protein S-palmitoylation prevents cognitive deficits in an experimental model of Alzheimer’s disease’ by Francesca Natale et al. was published in PNAS at 20:00 UK time on Monday 25 November 2024. 

DOI: 10.1073/pnas.2402604121

Declared interests

Eloy Rodríguez: Declares that he has no conflicts of interest

Dr Julia Dudley: no conflicts of interest

For all other experts, no reply to our request for DOIs was received.