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The results of a world-first clinical trial have shown that a new gene therapy shows promise in reducing the amount of harmful proteins that build up in the brains of Alzheimer’s patients, potentially slowing or reversing the disease.
Using the therapy on a small number of patients, researchers were able to halve the concentration of the tau protein in their brains, which is thought to be implicated in the cognitive decline seen in people with the condition, reports the report. IFL Science.
Alzheimer’s disease is famous in the scientific community for being considered the most difficult disease to understand. With animal models that may not represent it correctly and numerous dead-end hypotheses – which are promising in theory but fail in practice – research has continually resulted in disillusionment when it comes to creating a viable treatment.
Current understanding of the underlying cause of the disease rests on two main mechanisms: harmful accumulation of tau protein; and amyloid protein plaques. Both disintegrate as they form, preventing brain cells from communicating with each other and even causing neurons to die.
This research, recently published in Nature Medicine, focused on tau. Tau is an insoluble protein, encoded by the microtubule-associated tau protein (MAPT) gene, which forms tangles in the brains of Alzheimer’s patients, making it a prime target for therapies.
The new approach, designated BIIB080 (/IONIS-MAPTRx), targets MAPT with an oligonucleotide “gene silencer” (a small piece of DNA or RNA) that stops the gene from producing more tau.
Clinical trials are designed to see if the drug is safe for humans and well tolerated, not to see if it is effective in treating the disease. The researchers tested it on 46 patients with an average age of 66, with some receiving the drug by injection into the spinal cord, while others were given a placebo.
All patients in the group completed the trial and had only minor side effects, indicating that the treatment is safe. At the end of the trial, after 24 weeks, the investigators found a tau reduction of more than 50% in the central nervous system of the group receiving the highest dose, suggesting that the drug had a significant biological effect.
Researchers now need to move on to new clinical trials over a longer period of time to assess whether this effect really has an impact on Alzheimer’s symptoms.
It is usually in this next phase that drugs for the disease tend to fail, as translating these successes into symptom reduction is a difficult task – but this is one of the first promising results of a therapy of this type in a long time, said the IFL Science.
“We need more research to understand the extent to which the drug can slow the progression of the physical symptoms of the disease and to evaluate the drug in larger groups and with older people and in more diverse populations,” said Catherine Mummery, lead author of the study.
“But the results are a significant step towards demonstrating that we can successfully target tau (protein) with a gene silencing drug to slow down – or possibly even reverse – Alzheimer’s disease and other diseases caused by the accumulation of tau in the future,” he added.
ZAP // 
