A gene discovery has explained why current Alzheimer’s drugs don’t work for lots of patients, and why so many new drugs fail in clinical trials.

The acetylcholine receptor α7nAChR has long been a target of interest for Alzheimer’s drugs. The neurotransmitter acetylcholine is involved in memory and learning processes. Despite acetylcholine being linked to the development of Alzheimer’s, many drugs targeting the acetylcholine receptor have failed in clinical trials.

Scientists have suspected that the action of a human specific gene, CHRFAM7A, could be the reason why drugs that appear to be effective in the animal testing stage later fail in human clinical trials. The CHRFAM7A gene is a ‘fusion gene,’ coding for both the acetylcholine receptor and a kinase enzyme that phosphorylates proteins.

Stem cells were edited to express the CHRFAM7A gene. The uptake of amyloid beta protein was measured, as this protein has been found to form plaques in the brains of Alzheimer’s patients. It was found that CHRFAM7A modulated the uptake of amyloid beta.

However, further studies on humans found that only 75% of people have the CHRFAM7A gene. Those that did not have the gene respond better to the drugs currently available, which mainly target the acetylcholine receptor.
Both studies press the need for a more personalised approach to Alzheimer’s treatment.