If you know someone with Alzheimer’s, then you’ve probably witnessed the severe memory loss, the personality changes, and overall transformation of your loved one into a completely different person in a short period of time. Even if you haven’t seen the disease first-hand, chances are you’ve heard about the immense toll it takes not only on the affected person, but on those who surround him or her. More likely than not, you wish you could do something about it—but you know there’s little to be done, because science just hasn’t gone that far yet.
Recent research is finally taking a big step in the right direction: a lab at the University of Zurich has developed an antibody called Aducanumab that has been shown to markedly reduce the symptoms of Alzheimer’s in early clinical trials.
Alzheimer’s is primarily a disease of the brain. We still have much to learn about it, but scientists have identified the amyloid hypothesis as the most likely means by which the disease occurs. This hypothesis states that the brains of patients with Alzheimer’s have an excess of beta-amyloid plaques, which are pieces of a more sizable protein from nearby nerve cells. These plaques can aggregate and block nerve function at synapses, causing severe degeneration of cognitive function.
The research at the University of Zurich is unique because it’s the first of its kind to successfully use an antibody to treat the disease. Antibodies are commonly used by medical researchers in disease therapy because each version of the molecule has a region that very specifically binds to a particular target (and usually, only to that target). For example, if you were to get a blood transfusion with the wrong type of blood, your body would produce antibodies that would target the foreign blood cells, and the antibodies would serve as a signal to the immune system to destroy the foreign entity. Our bodies naturally produce antibodies, but researchers can also create them behind the lab bench. In this case, the researchers at the University of Zurich produced an antibody against the beta-amyloid plaques in Alzheimer’s. Once the antibody binds to the plaques, it triggers cells of the immune system to go after the antibodies and subsequently destroy the plaques.
To test the effectiveness of the antibody, the researchers first tried a version of it in a mouse model. In the mice, they could easily track the path of the antibody: it bound the plaques as they had hoped it would, and it reduced the concentration of the amyloid plaques in correlation with the dosage of the antibody. The best part of this recent discovery, however, is that the antibody was tested in humans, and the results look promising. In the study, patients with Alzheimer’s were given either monthly intravenous infusions of the antibody or a placebo for a period of one year. Those who received the antibody showed a slowing of cognitive decline as compared to placebo, indicating that the antibody was working to combat the symptoms of Alzheimer’s.
If the researchers find similar results in higher-level phase 3 clinical trials (which are wider in scale, with more test subjects, than lower-level trials and usually compare the new treatment to older treatments), then not only will there be strong support for the amyloid hypothesis, but patients and families may finally have a reliable treatment to count on.
This research hits pretty close to home for me. My great-aunt passed away a few years ago from a multitude of problems, but largely because of Alzheimer’s. The memory loss was bad—she could barely recognize her own children—but even worse were her violent reactions to things that she used to find commonplace. I fear that my grandmother, her sister, could one day be victim to the disease too, but thankfully my family hasn’t observed its symptoms in her.
For someone like me who is very interested in chemistry—especially chemical biology—and its applications to medical research, the scientists’ success in working with antibodies is especially interesting and thought-provoking. I hope to one day pursue an MD-PhD degree where I can combine the more human aspect of medicine—caring for patients—with my passion for discovery. In my eyes, the impact of this Alzheimer’s research merges lab-bench work with patient interaction and clinical drug administration to patients in a way that exemplifies the purpose of the dual degree altogether. I would like to engage in cancer research in the future, and I look forward to seeing how the potential of antibodies can be harnessed for other diseases, especially in the field of oncology.
Diane Rafizadeh is a sophomore in Jonathan Edwards College. Contact her at firstname.lastname@example.org.
(Featured Image courtesy of https://commons.wikimedia.org/wiki/File:Amyloid_02big1.jpg)