Recent Phase 3 Trials Shed Light on Gantenerumab’s Role in Alzheimer’s Treatment and Future Research Directions

Alzheimer’s disease (AD) is the most common cause of dementia, accounting for about 70% of dementia cases worldwide. AD is a neurodegenerative disorder that affects memory and behavior, leading to psychosocial changes and commonly affecting older people. Over time, thinking skills and the ability to carry out simple tasks are impaired. AD is caused by the accumulation of beta-amyloid plaques in the memory center and other locations in the brain, leading to the above symptoms. In the year 2020, the worldwide prevalence of AD was 55 million, and according to statistics, the number is predicted to double in the next 20 years.

Gantenerumab

Gantenerumab Credit: The New England Journal of Medicine

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Currently, there are only symptomatic medications approved for use, as there is no cure for the disease. These drugs regulate the activities of neurotransmitters, glutamate and acetylcholine, in the brain. The regulation of these neurotransmitters helps to improve symptoms. Recent pharmacological studies have focused on producing medications that target the production, accumulation, and clearance of amyloid beta protein. It is believed that anti-amyloid beta monoclonal antibodies can modify the course of AD. Though they have promising outcomes, none of these medications has proven effective in phase 3 trials thus far.

Hit or miss?

Recently, Dr. Randall Bateman and his colleagues performed two phase 3 drug trials called GRADUATE I and II, to improve cognitive and behavioral deterioration in Alzheimer’s patients. They suggested that the administration of an anti-amyloid beta immunoglobulin (anti-AB IgG1) monoclonal antibody called Gantenerumab, which has a special affinity for amyloid beta proteins, could clear the protein through a microglia-mediated process called phagocytosis and promote the clearance of the protein plaque. They also proposed that it affects cell biomarkers of the disease. Participants who had mild Alzheimer’s disease and were between the ages of 50 and 90 were recruited.

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Following the administration of Gantenerumab, the amyloid plaques were partially removed, and certain biomarkers of the disease showed improvement.

However, based on prior studies and predetermined predictions, the amount of amyloid plaque removal was less than predicted. The mean amyloid beta level remained raised even after the administration of the drug, and only 25% of the sample population had amyloid levels below the lower limit for amyloid positivity.

Clinical significance

The results from this study and other studies carried out in the past show that the use of drugs like Gantenerumab reduces amyloid plaque compared to placebo, but this does not lead to slower neurodegeneration. Alzheimer’s is currently a leading topic in biomedical research. The goal is to learn as much as we can about Alzheimer’s and other forms of dementia. We hope that new treatments will result from this increased understanding. Numerous possible methods are presently being researched globally.

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Conclusion

Alzheimer’s disease is a progressive illness that requires early diagnosis and treatment to achieve a better disease outcome. While Gantenerumab might not have had as much efficiency as we had hoped in slowing neurodegeneration, the door is still open for novel substances to be tried in the future.

References

Bateman, R. J., Smith, J., Donohue, M. C., Delmar, P., Abbas, R., Salloway, S., Wojtowicz, J., Blennow, K., Bittner, T., Black, S. E., Klein, G., Boada, M., Grimmer, T., Tamaoka, A., Perry, R. J., Turner, R. S., Watson, D., Woodward, M., Thanasopoulou, A., . . . Doody, R. S. (2023, November 16). Two Phase 3 Trials of Gantenerumab in Early Alzheimer’s Disease. The New England Journal of Medicine. Retrieved November 17, 2023, from https://doi.org/10.1056/nejmoa2304430