Alzheimer’s drugs ‘fail because of a patient’s DNA’: Scientists discover 75% of people carry a genetic mutation that makes three out of four dementia treatments ‘ineffective’
- May be why so many drugs work in animals trials but are ineffective in humans
- Gene CHRFAM7A is involved in memory and associated with Alzheimer’s
- CHRFAM7A is mutated in three out of four people who are ‘less likely to benefit’
Alzheimer’s drugs may fail because of a patient’s DNA, research suggests.
A study found a genetic mutation that three quarters of people carry may be why so many medications work in animals trials but are ineffective in humans.
The gene CHRFAM7A codes for a receptor for acetylcholine, which transmits impulses within the nervous system. Acetylcholine is involved in memory and has long been associated with Alzheimer’s.
Three out of four established Alzheimer’s drugs, and more in development, work to stimulate acetylcholine receptors.
CHRFAM7A is not typically carried by the animals used in Alzheimer’s studies but is mutated in three out of four people.
These unlucky patients are ‘less likely to benefit’ from dementia medications and require ‘personalised treatment’, the US researchers said.
Alzheimer’s drugs may fail because of a patient’s DNA, research suggests (stock)
The research was carried out by the University at Buffalo (UB) and led by Dr Kinga Szigeti, director of the Alzheimer‘s disease and memory disorders center.
Dementia affects 850,000 people in the UK, of which 62 per cent have Alzheimer’s, according to the Alzheimer’s Society.
And in the US, 5.8million people live with the condition, which is set to rise to nearly 14million by 2050, Alzheimer’s Association statistics show.
Alzheimer’s is incurable, with treatments only being able to temporarily relieve symptoms.
Dozens of drugs are under development, with billions of dollars being invested.
However, when it comes to treating Alzheimer’s, there are many more setbacks than successes.
This has been blamed on the wrong proteins being targeted, ambitiously trying to ‘cure’ the disease rather than prevent symptoms and patients simply being treated too late.
The UB researchers previously studied how CHRFAM7A and Alzheimer’s drugs interact in tissue in the laboratory.
To uncover how DNA influences treatment response, the scientists looked at data from a 10-year study with 345 patients by the Texas Alzheimer Research and Care Consortium.
Results revealed CHRFAM7A presents in two ‘flavours’.
The first is a functioning gene that a quarter of people carry, while the remaining 75 per cent have a ‘mutated’ version.
‘This splits the population one-to-three between non-carriers and carriers,’ Dr Szigeti said.
The results were presented at the Alzheimer’s Association International Conference in LA.
Three out of four Alzheimer’s drugs that are approved by the Food and Drug Administration in the US stimulate receptors that respond to acetylcholine.
CHRFAM7A specifically codes for an alpha 7 receptor for acetylcholine.
Drugs that target alpha 7 have been in development for more than a decade but have consistently failed when they enter clinical trials.
‘Since this human fusion gene was not present in the animal models and screening systems used to identify drugs, 75 per cent of Alzheimer’s patients who do carry this gene are less likely to benefit and therefore are at a disadvantage,’ Dr Szigeti said.
The study also found nerve cells that are ‘at risk’ of Alzheimer’s express alpha 7.
‘Our work confirms alpha 7 is a very important target for treating Alzheimer’s but the right model – a human model – has to be used when testing new drugs,’ Dr Szigeti said.
The results suggest patients require a personalised approach to their treatment based on their CHRFAM7A expression.