Could an Alzheimer’s vaccine prevent or treat the disease?

Could an Alzheimer's vaccine prevent or treat the disease?

A New Hope for Alzheimer’s Treatment: The Potential of a Novel Vaccine

Image Source: Henrik Sorensen/Getty Images

Finding a successful treatment for Alzheimer’s disease has long been a challenging and controversial endeavor. However, a recent breakthrough in research brings a glimmer of hope with the development of a new vaccine that targets a protein found in aging brain cells and blood vessels. The vaccine has shown promising results in mice, improving behavior and reducing levels of an amyloid-beta protein precursor. While this breakthrough raises excitement, the question of which molecules should be targeted in Alzheimer’s treatment research still looms.

The Controversy Surrounding Alzheimer’s Treatment Research

Traditionally, much of the focus in Alzheimer’s disease treatment research has centered around preventing the buildup of amyloid beta protein plaques in the brain, which are distinct features of the disease. Controversy arose when the FDA granted accelerated approval for the use of lecanemab (Leqembi) in treating early-stage Alzheimer’s disease. Questions were raised regarding its efficacy and side effects. Further controversy followed when pharmaceutical company Eli Lilly’s Alzheimer’s drug donanemab was not approved as expected, as more data was needed to determine efficacy.

In July 2022, controversy reached a peak following an investigation that alleged manipulation of images in a highly influential paper published in Nature in 2006, which confirmed the amyloid beta-hypothesis. These controversies reflect the high stakes involved in finding a drug target for Alzheimer’s disease, as the number of cases continues to rise, expected to reach 13 million by 2050 in the United States alone.

Dr. Santosh Kesari, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, highlighted the significance of the breakthrough. He stated that all currently approved drugs for Alzheimer’s treat symptoms rather than impacting the disease course. Lecanemab, an antibody drug, is the first drug aimed at targeting the amyloid protein, thought to be the underlying cause of the disease. This recent approval offers renewed hope in the field of Alzheimer’s treatment.

The Potential Targets for Alzheimer’s Treatment

While the amyloid beta protein has dominated Alzheimer’s treatment research, other mechanisms underlying the disease progression, such as inflammation, have also been under scrutiny. Inflammation plays a role in conditions like atherosclerosis, leading to debates about the potential link between the two diseases. Both conditions involve inflammation and vasculature, with certain APOE gene variants predisposing individuals to both diseases.

Researchers in Tokyo have spent a decade investigating a drug that could target both atherosclerosis and Alzheimer’s disease using mouse models. In recent studies, they identified that senescence-associated glycoprotein (SAGP-protein) is upregulated in immune and vascular endothelial cells in mouse models with atherosclerosis. Increased expression of this protein has been associated with a higher risk of both atherosclerosis and Alzheimer’s disease.

The research team developed a vaccine that targets older cells with high levels of SAGP-protein expression. Promisingly, their vaccine not only decreased the levels of amyloid-beta peptide, a precursor to amyloid beta-protein, but also improved the behavior of mouse models of Alzheimer’s disease, along with reducing levels of inflammatory molecules.

The Functioning of the Novel Vaccine

Dr. Chieh-Lun Hsiao, the lead author of the study, provided insight into the workings of the vaccine. The exact process of generating the vaccine is undisclosed; however, its design aims to eliminate or reduce cells that contain an abundance of the targeted protein, SAGP. Vaccination trains the immune system to recognize and react to specific targets. In this case, they hypothesized that cells with high SAGP expression are pathogenic or abnormal. The vaccine helps in developing immunity to recognize and remove or destroy these cells.

Limitations and Implications of the Novel Vaccine

Although the newly developed vaccine shows great potential, there are limitations and important considerations to take into account. Kath Intson, CEO of precision medicine startup Varient and a Ph.D. candidate at the University of Toronto, notes the need for further information on potential side effects and the consequences of targeting microglia, the brain’s immune cells. Removing a significant portion of the brain’s immune system could have unintended consequences.

Intson also raises concerns regarding the targeting of amyloid-beta peptide for treating Alzheimer’s disease. Accumulation of this peptide plays a protective role in the brain following acute injuries such as stroke or traumatic brain injury. Removing this vital and normal function from healthy patients could have implications for their health, especially in relation to other brain-damaging conditions.

A Glimmer of Hope

The development of a novel vaccine targeting a protein found in aging brain cells and blood vessels offers new possibilities in the treatment of Alzheimer’s disease. While controversies surrounding previous drug targets persist, this breakthrough highlights the importance of exploring alternative mechanisms underlying the disease progression. By broadening the scope of research and considering multiple targets, the chances of finding an effective Alzheimer’s treatment increase.

As researchers continue to delve into the mechanisms and potential side effects of the novel vaccine, there is a renewed sense of hope for the millions of individuals affected by this devastating disease. While challenges and limitations remain, advancements in Alzheimer’s treatment will undoubtedly shape the future of healthcare and offer a glimmer of hope to those affected, their families, and society as a whole.