March 2, 2024

Medical Trend

Medical News and Medical Resources

Targeted Drug Delivery for Alzheimer’s Disease Treatment

Breakthrough! Targeted Drug Delivery for Alzheimer’s Disease Treatment



Breakthrough! Targeted Drug Delivery for Alzheimer’s Disease Treatment

On January 3rd, a groundbreaking human study published in the New England Journal of Medicine revealed that the combination of focused ultrasound and monoclonal antibodies against β-amyloid protein can accelerate the clearance of β-amyloid plaques in the brains of Alzheimer’s disease patients.

Monoclonal antibody therapies targeting β-amyloid (Aβ), such as aducanumab, lecanemab, and donanemab, have shown the ability to reduce β-amyloid plaques and slow the progression of Alzheimer’s disease. However, the current limitation lies in the blood-brain barrier (BBB), a protective barrier between blood vessels and the brain, which hinders the accessibility of these promising antibody therapies to the brain. Over 98% of drugs find it challenging to penetrate the blood-brain barrier, requiring higher doses and more frequent treatments for systemic therapy.

Scientists at RNI used the Insightec-developed focused ultrasound system to safely and temporarily open the blood-brain barrier, allowing the anti-β-amyloid antibodies to enhance contact with specific brain regions. A FUS MRI-guided treatment helmet with over 1,000 ultrasound transducers was targeted to specific brain regions with high β-amyloid plaques.

After six months of antibody treatment, the average reduction in β-amyloid plaques (53% centiloid) in the brain regions with the open blood-brain barrier was 32% compared to regions without blood-brain barrier opening. This first-in-human proof-of-concept study demonstrated the safety of the method and showed a decrease in β-amyloid plaques measured by PET scans.

Researchers commented, “This is an exciting moment for treating Alzheimer’s disease. The next phase of clinical trials will begin this year, exploring how the combination of focused ultrasound and lecanemab antibodies can further accelerate the removal of β-amyloid in a shorter time.”


Alzheimer’s Disease (AD)

Alzheimer’s disease (AD), commonly known as dementia or senility, is the most common neurodegenerative disease in the elderly, characterized by a decline in memory and cognitive function.

AD, often referred to as the “long farewell” due to the gradual deterioration of brain function and memory, starts with mild memory loss in the early stages and progresses to the loss of communication and reaction abilities. In the advanced stages, patients become bedridden and heavily dependent on others.

The World Health Organization estimates that over 55 million people globally (8.1% of females and 5.4% of males aged 65 and older) suffered from dementia in 2019. It is projected to rise to 78 million by 2030 and reach 139 million by 2050, with approximately 60%-70% being Alzheimer’s disease (AD) patients.

Reports indicate that every 3 seconds, a new dementia patient is diagnosed globally.

The global costs associated with dementia-related care and treatment are expected to double from $1.3 trillion annually in 2019 to $2.8 trillion by 2030. Alzheimer’s disease has become a significant public health issue, severely impacting global population health and quality of life.

Currently, there is no cure for Alzheimer’s disease, and the progression cannot be reversed. Treatment can only slow down the deterioration of the condition. AD is a neurodegenerative disease primarily driven by the abnormal accumulation of β-amyloid plaques and abnormal phosphorylation of Tau protein. Most scientists believe that the development of Alzheimer’s disease is caused by the abnormal buildup of β-amyloid plaques in the brain, leading to extensive neuronal death.

Overview of Major Breakthroughs and Marketed Drugs for Alzheimer’s Disease

Alzheimer’s disease has long been considered a challenging field for pharmaceutical research, with a clinical failure rate of 99.6% for new drugs targeting Alzheimer’s disease. Major pharmaceutical companies such as Johnson & Johnson, Merck, Pfizer, and Roche have faced setbacks in this field. However, on June 7, 2021, a new antibody drug called Aduhelm, designed to treat Alzheimer’s disease-related mild cognitive impairment (MCI) and mild Alzheimer’s disease, received FDA approval for market entry, becoming the first FDA-approved AD treatment based on the β-amyloid hypothesis in nearly 20 years.

Aducanumab, marketed as Aduhelm, was developed by Biogen, and the FDA approved its market entry on June 7, 2021.

Although the anti-amyloid antibody aducanumab had previously received accelerated FDA approval, its market entry was controversial. Clinical trials showed that this monoclonal antibody could clear β-amyloid in the brain, but there was insufficient evidence to suggest that it could slow or stop the progression of Alzheimer’s disease.

Another AD drug, Lecanemab, showed promising results in Phase III clinical trials, demonstrating a 27% slowdown in cognitive decline and overall improvements in various indicators. It received full FDA approval for market entry on July 6, 2023.

Breakthrough! Targeted Drug Delivery for Alzheimer's Disease Treatment

Donanemab, another drug developed by Eli Lilly, significantly slowed the progression of early-stage Alzheimer’s disease, with a 60% reduction in cognitive and functional decline in the complete results of the TRAILBLAZER-ALZ 2 Phase III clinical study announced on July 17, 2023.

Although the road to development has been challenging, the emergence of Lecanemab and Donanemab heralds a new dawn for Alzheimer’s disease treatment.

On November 15, 2023, the complete Phase III data for the investigational drug Gantenerumab were published in the New England Journal of Medicine. Gantenerumab, a subcutaneously administered fully human anti-Aβ-IgG1 monoclonal antibody with high affinity for aggregated Aβ, has been tested for treating Alzheimer’s disease.

A challenge in Alzheimer’s disease treatment is the blood-brain barrier restricting the delivery of therapeutic drugs to brain tissue.

Future Prospects

Current drug development focuses on early-stage Alzheimer’s patients with confirmed β-amyloid deposition through brain imaging. Therefore, there is a need for better-targeted drugs.

Notably, monoclonal antibody therapies targeting β-amyloid, such as aducanumab, lecanemab, and donanemab, show promise in reducing β-amyloid plaques and slowing Alzheimer’s disease progression. However, these promising antibody therapies face a significant challenge in the blood-brain barrier (BBB) limiting the delivery of therapeutic drugs to brain tissue.

The combination of focused ultrasound and lecanemab antibodies to further accelerate the removal of β-amyloid in a shorter time represents a crucial breakthrough in improving this therapeutic approach.

While the road to developing Alzheimer’s disease drugs is extremely challenging, many scientists continue to strive to overcome research hurdles, aiming to find effective diagnostic methods and treatment drug targets. They also anticipate more effective drugs entering clinical practice in the future.

Scientists remain tirelessly committed, hoping to discover more effective treatment methods and, ultimately, a cure. As Dr. Marc Haut from the Rockefeller Neuroscience Institute (RNI) states, “We hope that our work may improve the outcomes for many other patients and their families dealing with Alzheimer’s disease.”

References

Public information from U.S. Business News, World Health Organization, New England Journal of Medicine, AD International Organization 2023 Report,

and official websites of Biogen, Eli Lilly, and other companies.
References from Biogen/Eisai, Lilly, and other official websites.

Breakthrough! Targeted Drug Delivery for Alzheimer’s Disease Treatment

(source:internet, reference only)


Disclaimer of medicaltrend.org


Important Note: The information provided is for informational purposes only and should not be considered as medical advice.