2023-05-03 12:20:27
About 1 million people live in France with Alzheimer’s disease and nearly 225,000 new cases are diagnosed each year. There is currently no treatment capable of curing this disease. Recently, researchers conducted a clinical trial on a mouse model to test the interest of gene therapy once morest Alzheimer’s disease. Results.
Alzheimer’s disease, the most common dementia
The Alzheimer’s disease is the shape of dementia the most frequent and its prevalence continues to increase from year to year. In recent years, researchers and physicians have acquired more precise knowledge of the physio-pathological mechanisms responsible for the disease. Their efforts focus mainly on two levels:
- Improve the diagnosis of the disease, by developing specific tests using easy-to-measure biomarkers;
- Develop treatments capable of curing the disease.
Currently, there is no treatment that can stop Alzheimer’s disease. This pathology is related to abnormal protein buildupTHE amyloid and tau proteins, in different brain regions. Previous studies have suggested that reducing the amount of tau protein in the brain may reduce signs of disease. In this context, researchers recently conducted a first clinical trial to assess a genetical therapy in the treatment of Alzheimer’s disease.
Gene therapy for Alzheimer’s disease?
The gene therapy developed by the researchers targets the expression of the gene coding for the tau protein. By inhibiting this expression, they seek to reduce the presence of tau protein and thus improve the clinical condition of patients suffering from mild Alzheimer’s disease. To evaluate their gene therapy, they conducted a Phase 1b, randomized, double-blind, placebo-controlled, multiple-escalating-dose clinical trial. The objective of this clinical trial was to evaluate the safety, pharmacokinetics and effect of gene therapy.
A total of 46 patients, with a mild form of Alzheimer’s disease were recruited for this clinical trial, conducted between 2017 and 2020. They were randomly divided into two groups:
- A group of 34 patients received every 4 or 12 weeks over a period of 13 weeks, increasing doses of gene therapy (administered intrathecally);
- A group of 12 patients received a placebo.
Switching off the gene encoding tau protein to fight the effects of Alzheimer’s disease
After a post-treatment period of 23 weeks, endpoints were safety, uptake of gene therapy into cerebrospinal fluid, and total tau protein concentration in cerebrospinal fluid (cerebrospinal fluid, or cerebrospinal fluid, is the liquid in which the brain and spinal cord bathe). Mild or moderate adverse events were observed in 94% and 75% of patients in the “test” and “placebo” groups, respectively. The most frequently observed side effect was headache. In the end, more than 90% of the patients continued the study until its end.
In terms of evaluation, a dose-dependent reduction in the total concentration of tau proteins in the cerebrospinal fluid was observed thanks to gene therapy. The mean reduction was more than 50%, compared to the concentration at the start of the study, 24 weeks following a final dose of 60 mg (4-dose regimen) or 115 mg (2-dose regimen). This first clinical trial on gene therapy targeting the tau protein reveals that it is possible to reduce the concentration of tau proteins in subjects with mild Alzheimer’s disease. A promising trial, even if it now remains to be proven that reducing the concentration of tau proteins significantly improves the clinical condition of patients, and in what proportions.
Estelle B., Doctor of Pharmacy
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#Gene #therapy #Alzheimers #disease
