A study found new hope for the treatment of Alzheimer's disease

A study found new hope for the treatment of Alzheimer's disease

Worldwide cases of Alzheimer's disease are expected to reach more than 55 million by 2020, according to Alzheimer's disease International. Increasing to 78 million in 2030 and 139 million in 2050, this number will nearly double every 20 years. According to the WHO Global Status Report for 2021, dementia costs the world's economy more than USD 1.3 trillion years, with an expected rise to USD 2.8 trillion by 2030.

Most medications created to treat Alzheimer's disease have been ineffective, partly because they target the wrong biomarkers and people who are already showing symptoms of the illness. However, many of the memory and cognitively important brain cells are likely already destroyed and beyond repair by the time symptoms start to appear. For the first time, theranostics has been used by Professor Shai Rahimipour of the Chemistry Department at Bar-Ilan University in Israel to identify and treat the early, pre-symptomatic indications of Alzheimer's disease. Rahimipour's innovative method has attracted a lot of interest in the scientific community since it shows promise in stopping the disease's progression before the beginning of irreversible brain cell destruction.

Amyloid beta, a tiny protein, misfolds in Alzheimer's disease to form intermediates that combine to form fibrils and plaques, larger macromolecular structures. Scientists have long held the belief that plaques, which are visible under a microscope, are the origin of the neuronal damage in the origin of Alzheimer's disease. To develop chemicals and antibodies that target and inhibit the production of fibrils and plaques, many clinical studies and billions of dollars have been conducted over more than 25 years. Such treatments were ineffective and had unpleasant side effects. Fibrils and plaques were initially thought to be safe, but more recently, soluble intermediates known as oligomers have come to be blamed for this deceptive illness.
The Biogen/Essai antibodies Aducanumab and Lecanemab have been approved by the US Food and Drug Administration (FDA), and recent clinical trials using antibodies to target oligomers have demonstrated encouraging outcomes. The need for better therapy and techniques for early Alzheimer's disease detection to enhance the standard of care is highlighted by controversy about the efficacy and noteworthy adverse effects including microhemorrhages and brain enlargement. Furthermore, because the blood-brain barrier limits the penetration of proteins and antibodies, the majority of antibodies do not adequately reach the brain. Rahimipour and his team overcame these obstacles by creating tiny, abiotic, and drug-able cyclic peptides that have shown potential in animal models for early Alzheimer's disease pre-symptomatic diagnosis and oligomer-targeted treatment. The formation of oligomers was entirely prevented when these molecules were mixed in a test tube with the tiny protein amyloid beta, and no further aggregation took place. 

The researchers then treated human neurons with the hazardous oligomers and cyclic peptides in the following step. The majority of the neurons were still alive, while those exposed to the oligomers without cyclic peptides in the control group suffered severe damage and eventually died. The effectiveness of the cyclic peptides was then examined in transgenic. roundworms that exhibit symptoms similar to those of Alzheimer's disease. By preventing the formation of early toxic oligomers, the researchers found that feeding the worms cyclic peptides significantly increased their survival and eliminated the onset of the disease. This study implies that the aggregation process, even before oligomers are formed, can be prevented at the very early stages of the disease.

A pre-symptomatic diagnosis was then made utilizing the Positron Emission Tomography (PET) method, which is frequently used in hospitals, on transgenic mice using a radioactive variant of the cyclic peptides. To their great joy, the molecule identified early amyloid beta oligomers for the first time in presymptomatic mice's thalamus, which transmits motor and sensory impulses to the cerebral cortex, before they spread to other brain regions. In other words, they were able to predict the disease's development before amyloid fibrils and plaques formed and before Alzheimer's disease symptoms showed up! After that, the cyclic peptides were administered to the transgenic mice at the pre-symptomatic stage, and their memory abilities and the number of amyloid beta oligomers in their brains were tracked over time. The scientists discovered using molecular imaging that the mice didn't produce a significant number of oligomers and, as a result, didn't show any symptoms of Alzheimer's.

"In these animal models, we have successfully prevented the illness even before oligomers are formed. Our synthetic molecules have several significant advantages over natural antibodies, including the fact that they are not immunogenic and stay in the body for a far longer period, requiring potentially fewer injections or applications "Prof. Rahimipour stated. The molecules, unlike antibodies, penetrate the blood-brain barrier fairly easily, and our extensive programme of investigations has found no indication of harm, the expert added. 


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