FDA-approved drug to treat liver infections could curb Alzheimer’s

A breakthrough drug designed to treat liver infections could be an unexpected therapeutic for people with Alzheimer’s disease.

Scientists found lonafarnib, an FDA-approved drug, curbed brain degeneration and improved behavioral symptoms in mice.

The drug was originally designated by the Food and Drug Administration as a therapy for hepatitis D, a liver infection virus transmitted through body fluids. 

In the new study, scientists genetically engineered mice to develop tangles of tau, a protein thought to cause Alzheimer’s.

But lonafarnib prevented their formation.   

Dr Israel Hernandez, from the University of California, said: ‘Although tau-related diseases including Alzheimer’s disease and chronic traumatic encephalopathy are serious public health problems, no disease-modifying treatment currently exists for these conditions.

‘Generally, approaches to treatment have directly targeted the tau protein.

‘However, few pharmacologic interventions directed toward tau pathways have reached clinical trials.

‘Interventions in upstream pathways have shown some efficacy in animal models, but none of these approaches has had success in human clinical trials to date.’

Researchers from the University of California identified a new pathway that promotes the degradation of tau via lysosomes – subcellular structures that break down molecules.

They found that this pathway cleared tau proteins by preventing certain enzymes and proteins from interacting with neurons.

The researchers then investigated the potential of lonafarnib in mice, which has been extensively studied as a treatment for hepatitis D and Progeria – a rare ageing disorder.

Chronic treatment with the drug boosted tau degradation, preserved brain size and prevented behavioural deficits such as obsessive circling in mice with dementia.

The authors say the pathway could be a ‘druggable target’ in tauopathies and other neurodegenerative diseases that feature dysfunctional protein degradation.

The study was published in the journal Science Translational Medicine. 

Dr Rosa Sancho, Head of Research from Alzheimer’s Research UK said: ‘The diseases that cause dementia are incredibly complex and many biological processes drive their progression.

‘Lonafarnib should be explored as a potential way to target the tau protein, but this early work in mice still has a long way to go before we’ll know whether it could be a medicine that benefits people with dementia.’

She added: ‘Tau is a key player in a number of the diseases that cause dementia and a promising focus for drug discovery efforts worldwide.

‘This study suggests that treatment with lonafarnib may only be effective in the early stages of disease, re-enforcing the importance of research into the early detection of diseases like Alzheimer’s.

‘With almost a million people in the UK living with dementia today, we must double efforts towards finding new treatments.

‘The Alzheimer’s Research UK Drug Discovery Alliance is currently working on over 20 promising drug discovery projects, with the goal of bringing new medicines to people with dementia as soon as possible.’