Dementia could be halted in future with gene therapy, a study suggests.

Scientists tested a gene that blocks harmful changes to the brain on mice with a rodent version of the condition.

After four months the mice showed a marked reduction in clinical symptoms and performed as well in memory tasks as healthy mice.

However, experts are urging caution because the research is at a very early stage. And mouse “models” of Alzheimer’s do not precisely mirror the disease in humans.

But lead researcher Dr Magdalena Sastre, from Imperial College London, hopes the study will provide a spring board for developing gene therapy treatments that either prevent Alzheimer’s or stop it progressing.


Scientists modified a virus to carry a gene that prevents a harmful substance from forming on the brain

She said: “Although these findings are very early they suggest this gene therapy may have potential therapeutic use for patients. There are many hurdles to overcome and, at the moment, the only way to deliver the gene is via an injection directly into the brain. However this proof of concept study shows this approach warrants further investigation. We are still years from using this in the clinic. However, in a disease that urgently needs new options for patients, this work provides hope for future therapies.”

The treatment used a harmless modified virus to carry the gene, known as PGC1-alpha, into parts of the brain most affected by Alzheimer’s.

The gene is believed to block formation of a peptide – a protein fragment – called beta-amyloid that builds up in sticky clumps in the brains of people with the disease.

Deposits of beta-amyloid are thought to trigger the death of brain cells, leading to dementia symptoms such as loss of memory.

In the study, the virus carrying the gene was injected into the hippocampus and cortex regions of the brain.

Damage to the hippocampus affects short-term memory, so that recent events such as a conversation or what a person ate for breakfast are forgotten.

It also has an impact on orientation and increases the chances of getting lost while out for a walk or driving home from the shops.

The cortex is involved in long-term memory, reasoning, thinking and mood. Cell death in this area can lead to symptoms such as depression, or struggling to cope with a supermarket checkout, dress oneself, or cook a familiar recipe.

The mice were treated at an early stage of disease progression, before they had developed amyloid deposits or “plaques” in their brains.

After four months mice given the gene therapy had very few amyloid plaques, which were numerous in untreated animals.

The memory tests included watching how mice responded when a familiar object in their cage was replaced with a new one. Healthy mice explored the new object for longer, having noticed it was different from the one they remembered.

Treated mice appeared to suffer no loss of brain cells in the hippocampus. They were also less likely to experience toxic inflammatory effects, which cause further cell damage and are linked to Alzheimer’s.


The therapy helped to reduce clinical symptoms in mice

PGC1-alpha codes for a protein that plays a role in metabolic processes in the body, including sugar regulation and the breakdown of fats.

Dr David Reynolds, chief scientific officer at the charity Alzheimer’s Research UK, which co-funded the research reported in the journal Proceedings of the National Academy of Sciences, said: “There are currently no treatments able to halt the progression of damage in Alzheimer’s, so studies like this are important for highlighting new and innovative approaches to take us towards that goal.

“This research sets a foundation for exploring gene therapy as a treatment strategy for Alzheimer’s disease, but further studies are needed to establish whether gene therapy would be safe, effective and practical to use in people with the disease.

“The findings support PGC1-alpha as a potential target for the development of new medicines, which is a promising step on the road towards developing treatments for this devastating condition.”

Rob Howard, Professor of Old Age Psychiatry at University College London, said that, while promising, the work should be viewed as a “proof of concept” in blocking the development of one Alzheimer’s brain symptom.

He added: “This may or may not translate into benefits when applied to humans, but is an important first step. Before clinical effectiveness trials of this technology in Alzheimer patients can be conducted, I would anticipate several years of early phase and safety studies. Only time will tell.”

Fellow expert Dr Mark Dallas, lecturer in cellular and molecular neuroscience at the University of Reading, said: “Gene therapy has a chequered history and therefore it will need to be tested more extensively before we can exploit the potential of gene therapy for Alzheimer’s disease.”