This therapeutic composition administers bacteriophages to eliminate specific bacterial strains that induce toxic protein aggregation and ultimately contribute to neurodegenerative protein conformational diseases (PCDs). PCDs, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis, are leading causes of death and disability worldwide. Currently, over 40 million people live with dementia globally, and this number is estimated to increase two to three-fold by 2050. However, despite their increasing prevalence, the exact mechanisms behind them and potential therapeutic targets remain unclear. There are no known effective treatments or preventative strategies.
Neurodegenerative PCDs are characterized by impairment in protein folding homeostasis, also known as proteostasis, inducing toxic protein aggregation in the brain and eventually leading to tissue death. Recent evidence hints at a link between the gut microbiota and neurodegenerative PCDs. However, the gut microbiota is a complex and dynamic ecosystem, and dissecting the contribution of specific bacteria to the stability of the proteins associated with these diseases remains challenging. Additionally, the available metagenomic evidence reveals a correlational association of bacteria with PCDs.
Researchers at the University of Florida have developed a screening tool for identifying the unique bacterial isolates and their specific role in the aggregation of PCDs-associated proteins. Leveraging this unprecedented knowledge, they have designed a therapeutic composition to enrich proteostasis-enhancing bacteria and eliminate species associated with protein aggregation.
Combination of proteotoxicity-targeting bacteriophages and proteostasis-enhancing bacteria to treat neurodegenerative protein conformational diseases
Disruption of proteostasis, leading to protein misfolding and aggregation, is a hallmark of neurodegenerative protein conformational diseases (PCDs). Despite PCDs emerging as the leading cause of death among the elderly worldwide, there is no effective treatment or cure. Evidence suggests that gut bacteria influence the pathogenesis of PCDs, though the specific role of individual microbes remains unclear. Researchers at the University of Florida have developed a screening system leading to the characterization of over 220 unique bacterial species from the Human Microbiome Project for their role in the aggregation of disease-associated proteins. Additionally, they discovered that bacterial colonization of the gut affects host proteostasis in both proximal and distal tissues, including neurons. By identifying the specific bacteria contributing to proteostasis enhancement and disruption, they have developed a combination therapy to modulate the gut microbiota composition and mitigate protein aggregation.
This therapeutic administers bacteriophages to eliminate previously identified detrimental bacteria from the host gut, such as Pseudomonas, Shigella, Achromobacter, Klebsiella, or Escherichia. Additionally, it includes administering a Prevotella species, typically depleted in patients with different PCDs. This strategy further involves analyzing and monitoring the abundance of these bacteria in patient stool samples to determine the specific species to target or enrich. By promoting the enrichment of proteostasis-enhancing bacteria and identifying and targeting harmful microbes, this therapeutic enables targeted treatment of neurodegenerative PCDs.