Written by Alex Egipto
For a disease that is projected to have $1.9 billion in research funding for 2018 alone, it’s a bit shocking that 99% of the drugs developed for Alzheimer’s have failed . Patients with Alzheimer’s disease suffer from a host of neurological problems, such as impaired memory, speech, and motor function, that worsen over time as the brain physically degrades. The original view on what causes such a debilitating disease centers on two key proteins called tau and amyloid. The former, tau, is a protein involved in the making of microtubules, structures that assist with cellular movement . The latter, amyloid, is not well understood, but is known to be made by a variety of cells in the body such as neurons, platelets, and skeletal muscle cells . Accumulations of both of these proteins are often seen in the brains of Alzheimer’s patients as hallmarks of the disease . These aggregates are seen by researchers as the source of the brain’s physical deterioration and the cause of neurological problems associated with the disease.
Given the high failure rate of the drugs developed for this disease, it calls into question whether amyloid and tau are the right targets for treatment of Alzheimer’s disease. Researchers from the pharmaceutical company Cortexyme have found that a bacteria called P. gingivalis may be a key player in causing the deterioration of the brain in Alzheimer’s. Surprisingly, this same bacteria is normally involved in periodontitis, which is more commonly known as gum disease. Gum disease is characterized by the destruction of the connective tissue and teeth after the patient has been infected and P. gingivalis is highlighted as one of the main bacteria involved in causing this disease . P. gingivalis secretes three proteins that are necessary for its survival: RgpA, RgpB, and Kgp, all of which are known as “gingipains.”
Researchers from Cortexyme were able to connect these gingipains to Alzheimer’s by revealing their involvement in key hallmarks of the disease. For example, when comparing gingipain concentrations in the brain with tau and amyloid concentrations in the brain, they were able to find a significant correlation between the two . The researchers also discovered how gingipains were fragmenting, or breaking up, tau to make it easier for them to accumulate and cause problems in the brain . Additionally, gingipains were also found in the hippocampus of brains with Alzheimer’s. The hippocampus is the structure in the brain primarily concerned with memory and is often the first area in the brain to become damaged because of the disease . Given how memory loss is a key symptom associated with Alzheimer’s, the presence of gingipains here further suggests their involvement in causing the disease. Finally, when testing a combination of gingipain inhibitors in mice with Alzheimer’s, researchers were able to effectively block cell death induced by P. gingivalis when antibiotics could not .
As these inhibitors pass more trial phases and testing, we become one step closer to stopping a disease that has proven elusive in its primary cause, debilitating in its symptoms, and far-reaching with how much it can affect not just the patient, but those who care for them as well.
Edited by Ariel Min
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