A CryoDAO Project

Combination Medication Therapy for High-Quality Cryopreservation

Combination Medication Therapy for High-Quality Cryopreservation
Researchers
Dr. Emil Kendziorra, Aschwin De Wolf
Dr. Emil Kendziorra
Aschwin De Wolf
Funding

$200,000

Initiated
11.2.2022

Project Overview

Human Cryopreservation has recently gained renewed interest by a growing selection of the longevity community - even going so far that some leaders are switching their main occupation to the field. While resuscitation from cryogenic temperatures is still very much in the realm of basic science, cryopreservations are being done regularly as a last-choice for people interested in living longer than possible with current medical technology. Currently, human cryopreservation can only be practiced as a post-mortem procedure. This limitation entails that a credible protocol must be in place to rapidly stabilize the person after pronouncement of legal death to to prevent further deterioration of the patient. Contemporary human cryopreservation stabilization protocols are aimed at (1) restoring blood circulation to the brain (2) rapid induction of hypothermia (3) administration of a series of stabilization medications. Contemporary stabilization entails a long list of stabilization medications that are administered over a prolonged time course. We propose a single multi-model stabilization solution that can depress cerebral metabolism, inhibit blood coagulation, and mitigate cerebral ischemia to significantly and relevantly improve the quality of the average cryopreservation case.

Challenge

While Human Cryopreservation holds tremendous potential it is still a majorly underfunded sector of the longevity and life extension ecosystem. Even comparatively modest funding amounts can lead to significant and relevant impact. One low-hanging fruit are medication stabilization protocols. There are three challenges with contemporary human cryopreservation medication stabilization protocols. Despite the long lists of medications that have been used in cryonics protocols, pilot experiments have shown that only sodium citrate and heparin confer clear benefits on mitigating ischemia-induced perfusion impairment. In ideal circumstances, these compounds are administered right after circulatory arrest because they are estimated to lose their efficacy between 15 and 30 minutes post-mortem. Timely administration would be further favored if the effective compounds are combined in one, simple-to-administer, aqueous solution. For this solution to be practical and permit wide-spread local distribution in the field, it would not include any (regulated) pharmaceuticals but just a solution of chemicals that are readily available.

Opportunity

We propose to research, develop, and validate a solution that consists of at least one antithrombotic agent, one non-anesthetic compound that depresses brain metabolism, and one neuroprotectant. This solution can be administered immediately after pronouncement of legal death. We aim to validate this solution in an in-situ rat brain cryopreservation model with elimination of ice formation as a clinical endpoint. Our model provides for a non-ischemic control, an experimental group of 2 hours of normothermic ischemia, and a 2 normothermic ischemia experimental group in which we administer the solution. We expect to see significant improvement in mitigation of perfusion impairment and reduction of ice formation after cryopreservation in the group that received the multi-model solution immediately upon death. Successful development and validation of such a multi-modal solution would strongly streamline and simplify cryonics stabilization procedures and even hold promise for the treatment of out-of-hospital cardiac arrest and stroke in mainstream medicine. Positive results could be the base for novel IP regarding formulation and/or delivery methods to improve cryopreservation quality. Preliminary data shows that a few of the tested components have beneficial effects on the sub-factors determining preservation quality. Results from the proposed study will provide critical preclinical IP to support commercializing a Combination Medication Therapy for High-Quality Cryopreservation, which the investigator(s) intend do with support from CryoDAO.