Aducanumab: A new hope for Alzheimer’s disease treatment

While many other diseases take a person’s life, there’s also a few ones which gradually steal life away while a person is still technically alive & functioning, Alzheimer’s is one of the latter type. We all probably have seen the movie ‘The Notebook’, where we see how a dear one, suffering from Alzheimer’s disease becomes a total stranger. Even if we haven’t personally known an Alzheimer’s patient, we can imagine the pain & sufferings undergone by the patients & their families. According to a report sponsored by WHO in May 2018, Alzheimer’s is one of the leading causes of death, contributing to more deaths than cancer, diabetes, tuberculosis & road accidents.¹

 

As the most common form of dementia, Alzheimer’s disease is a neurodegenerative disease that is characterized by accumulation of extracellular amyloid beta plaques & intracellular neurofibrillary tangles. Recent studies support the idea that the accumulation of amyloid beta (Aβ) in brain is caused by an imbalance between the production and clearance of Aβ.² The most common symptoms of the disease are: memory loss, confusion, mood swings, disorientation and in severe cases death of brain cells & loss of brain activity leading to death.

 

Figure 1. A schematic of brain cells of a healthy patient (left) and one diagnosed with Alzheimer’s disease.³

 

Scientists have been looking for antibody-based immunotherapy against Aβ (Amyloid β) to enhance the clearance or reduce the neurotoxic effects of Aβ plaques. Aducanumab is a human monoclonal antibody that selectively targets Aβ plaques. Aducanumab can enter the brain by crossing the blood brain barrier. Once inside the brain, Aducanumab binds parenchymal Aβ, and reduces the extent of Aβ plaques. Aducanumab was developed using the human memory B cells. Human memory B cell is known to be active against the aggregation of β-amyloid. The methodology used involved screening the human memory B cells to identify antibodies that selectively binds the aggregated forms of β-amyloid.  The antibodies were then cloned and sequenced to develop the recombinant form, the drug Aducanumab.⁴

 

Aducanumab reduces brain Aβ plaques in a dose- and time-dependent manner in patients with prodromal or mild Alzheimer’s.⁴ Placebo & 3 different doses of 3mg/kg, 6mg/kg, 10mg/kg were administered intravenously every month in 165 patients in 33 sites of USA over the course of 1 year. The results came out fairly positive, showing significant reduction in the Aβ plaques. A comparative study of brain scan images of Alzheimer’s patients before and after the treatment is given in Figure-2. Common side effects of the treatment were ARIA (Amyloid related imaging abnormalities), headache, UTI (Urinary tract infection) & upper respiratory tract infection.

 

 

Figure 2.  PET (Position Emission Tomography) images of the Alzheimer’s patients before and after Aducanumab treatment. Red color indicating the plaque.⁴

 

Though many more steps and trials are required to finally approve the drug for its intended use, it’s very encouraging that we may finally have a treatment for Alzheimer’s disease that after decades of efforts. So, it can be hoped now that in a few years, there will be a drug to use against Alzheimer’s disease which will  save many lives & bypass a significant amount of  sufferings. It seems like the prayers of Alzheimer’s patients & their families are finally answered.

 

References:

1. World Health Organization (WHO), web accessed on 9/25/2018
   http://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death
    
2. Kristin R Wildsmith, Monica Holley, Julie C Savage, Rebecca Skerrett and Gary E Landreth (2013). “Evidence for impaired amyloid β clearance in Alzheimer’s disease”. Alzheimer’s Research & Therapy. 5:33
    
3. Hooper NM (2005). “Roles of Proteolysis and Lipid Rafts in the Processing of the Amyloid Precursor Protein and Prion Protein”. Biochemical Society Transactions. 33(Pt 2):335–38
    
4. Jeff Sevigny, Ping Chiao, Thierry Bussière, Paul H. Weinreb, Leslie Williams, Marcel Maier, Robert Dunstan, Stephen Salloway, Tianle Chen, Yan Ling, John O’Gorman, Fang Qian, Mahin Arastu, Mingwei Li, Sowmya Chollate, Melanie S. Brennan, Omar Quintero-Monzon, Robert H. Scannevin, H. Moore Arnold, Thomas Engber, Kenneth Rhodes, James Ferrero, Yaming Hang, Alvydas Mikulskis, Jan Grimm, Christoph Hock, Roger M. Nitsch2, Alfred Sandrock (2016). “The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease”. Nature. 53: 50-57
    
    
   By Iris Begum, a PhD student in Chemistry at the University of Kentucky