Alkahest has announced plans to launch a Phase 2 human trial that aims to address cognitive impairment and takes the unusual approach of using an external medical device that filters a harmful protein from the blood of end-stage renal disease patients.
The medical device, known as an AKST1210, will be connected in-line with a haemodialysis machine. The AKST1210 is designed to filter out and remove a protein called Beta-2 microglobulin (B2M), which was identified in a 2015 study by Dr. Saul Villeda, who confirmed its role as a pro-aging factor present in old blood .
B2M is an immune-associated protein with harmful, pro-inflammatory activity, and its presence has been shown to impair cognitive ability in animal studies. B2M is a problem for patients on long-term hemodialysis, as it can aggregate into amyloid fibers that deposit in joint spaces, a disease known as dialysis-related amyloidosis, and is thought to contribute to cognitive impairment in patients on hemodialysis for end-stage renal disease.
The following is an extract from Alkahest’s official press release:
SAN CARLOS, Calif., June 01, 2020 (GLOBE NEWSWIRE) — Alkahest Inc., a clinical stage biotechnology company focused on discovering and developing transformative therapies to treat age-related diseases, today announced the initiation of a clinical study to explore the use of an extracorporeal medical device to remove excess Beta-2 microglobulin (B2M) from circulation for the treatment of cognitive impairment in patients undergoing hemodialysis for end stage renal disease (ESRD).
“A large proportion of individuals with end-stage renal disease who receive hemodialysis have cognitive impairment, which may be associated with reduced ability for self-care, poor adherence to dietary and fluid restrictions, and poor outcomes,” said Karoly Nikolich, Ph.D., chief executive officer of Alkahest. “Alkahest’s preclinical research has demonstrated that Beta-2 microglobulin, which is present at higher levels in older individuals, is drastically elevated in patients undergoing dialysis and may contribute to the high prevalence of cognitive impairment in these individuals. By reducing the amount of B2M in the plasma, we hope to introduce an effective way to lessen this impairment and allow patients on hemodialysis for ESRD to achieve improved treatment outcomes and quality of life.”
AKST1210-201 is a randomized, double-blind, feasibility and tolerability study investigating the use of the AKST1210 device connected to the dialysis circuit in 20 subjects with ESRD and cognitive impairment over a period of 20 weeks. Key objectives are safety and tolerability, as well as feasibility of conducting clinical trials with AKST1210 in this setting. Secondary objectives include measurement of removal of B2M, as well as improvements in clinical measures of cognitive, functional and quality of life assessments.
The B2M protein is one of a number of proteins that have been observed to rise with age, and reducing its presence may help reduce the risk of cognitive impairment for patients on hemodialysis. If the trial is successful, then Alkahest has selected a good therapeutic target with an approach that should be relatively easy to implement.
 Smith, L. K., He, Y., Park, J. S., Bieri, G., Snethlage, C. E., Lin, K., … & Wheatley, E. G. (2015). [beta] 2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis. Nature medicine, 21(8), 932-937.