Gene therapy using a viral vector that delivers the human nerve growth factor (NGF) gene to the basal nucleus of Meinert has demonstrated high safety in patients with mild to moderate Alzheimer's disease, according to Pannochka, an online publication for girls and women aged 14 to 35. net These are the results of the first human trial of an innovative therapy reported at the Alzheimer's Clinical Research Conference in San Diego.

" bartus. Cholinesterase inhibitors available today, according to the scientist, "

Dr. Bartus, who is the president of San Diego-based RTBioconsultants, said: “Their effects on the cholinergic system are not optimal, they do not regenerate nerve cells, do not protect neurons from cell death, and do not affect lost neuronal function.. Of course, drugs give some improvement, but their level of effectiveness is low, and they do not improve symptoms in all patients.. Moreover, they do not affect the further progression of Alzheimer's disease in any way..

Neurotropic therapy with nerve growth factor should overcome all these shortcomings and give doctors a more powerful tool than current drug therapy.. Decades of research in animal models suggest that nerve growth factor "

Dr. Bartus said: “There are at least two significant barriers to the adoption of this technology.. First, Alzheimer's disease is extremely complex, so targeting therapy plays a very important role.. The correct choice of cholinergic target neurons is a real challenge, since it is their degeneration that is the main cause of memory loss..

The second obstacle, according to the doctor, is the need to influence the cholinergic neurons of the basal nucleus of Meinert, while avoiding affecting other populations of neurons.. 20 years ago, in practice, this was very difficult to implement. In the past decade, gene therapy combined with stereotaxic surgery has allowed the treatment of.

Using new technologies, Dr. Bartus and his colleagues at Ceregene, where the researcher has served as chief scientist for over 10 years, have developed a viral vector that delivers human nerve growth factor (AAV2-NGF, or CERE-110) into cells..

“You can think of this as a biopharmaceutical that, when administered to a patient, causes NGF gene expression in target neurons, and in this way supports cholinergic nerve cells.. Preclinical studies have demonstrated a strong dose-dependent effect on target neurons, with no side effects or toxicity, even after very high doses in animals.. It was quite unusual, and very encouraging for us, ”commented the results of his research, Dr..

Dr. Bartus at this conference presented the results of a phase I clinical study: data from 10 patients aged 50 to 79 years with mild to moderate Alzheimer's disease who received three different doses of AAV2-NGF via bilateral stereotaxic injection into the basal nucleus of Meynert. Dose A was 1.2x1010 viral particles, dose B was 5.8x1010 viral particles, and dose C was 1.2x1011.

Patients were observed for 24 months, studying the safety and preliminary evaluating the effectiveness of gene therapy. For this, positron emission scanning with 18-fluorodeoxyglucose was used before the start of the study, and then after 6, 12 and 24 months.. Neurophysiological tests were also used, which included the ADAS-Cog Alzheimer's Cognitive Assessment Scale.. The computer software made it possible to build detailed 3D models of Meinert's nucleus basalis "

Dr. Bartus reported that AAV2-NGF was safe and well tolerated throughout the 24 months of treatment.. The side effects that have been reported are related to the surgical procedure itself and resolve shortly after the procedure (headache).

Positron emission tomography showed no signs of accelerated neuronal degeneration, the autopsy of three patients (who died of various causes during these 2 years) confirmed the active gene-mediated expression of NGF directly in the basal nucleus of Meinert.

Scientists observed some deterioration in ADAS-Cog and other neurophysiological tests. "

These results provide grounds for a phase II clinical trial to be funded by the US National Institutes of Health as one of the most important studies in the treatment of Alzheimer's disease..

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