Project Team

David Putrino, PhD, Director of Rehabilitation Innovation for the Mt Sinai Health System, Associate Professor of Rehabilitation Medicine at the Icahn School of Medicine at Mt Sinai.

Amy Proal, PhD, President/Chief Scientific Officer, PolyBio Research Foundation

Mackenzie Doerstling, Program Manager, Division of Rehabilitation Innovation, Icahn School of Medicine at Mount Sinai

Project Summary:

Clinical trial team member Dr. Amy Proal

A clinical trial to test if the fibrinolytic enzyme Lumbrokinase improves symptoms and mitigates blood clotting issues or platelet hyperactivation in patients with LongCOVID, ME/CFS, & LongLyme disease. Small microclot deposits previously identified in LongCOVID and ME/CFS blood will be measured before and after treatment to determine if Lumbrokinase disrupts their formation. The LongLyme arm of the trial is supported via the Steve & Alexandra Cohen Foundation’s Clinical Trials Network Coordinating Center for Lyme and other Tick-Borne Diseases.

Project background:

The release of pathogen products into blood during acute or chronic disease can contribute to hypercoagulation and platelet hyperactivation. For example, small fibrin/amyloid microclots have been identified in LongCOVID blood. The SARS-CoV-2 S1 protein may “seed” their formation by inducing a type of fibrinogen resistant to breakdown that becomes part of clot structure. Because platelets have receptors that recognize dozens of viral and bacterial proteins, pathogens implicated in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) – such as the herpesviruses and enteroviruses – may also stimulate their activity. In Lyme disease, Borrelia burgdorferi sheds peptidoglycan – a component of its cell wall envelope that activates platelets and neutrophils, potentially leading to coagulation-associated signaling, including signaling that promotes the conversion of fibrinogen into fibrin (a central component of fibrin/amyloid microclot deposits).

Platelets have receptors that recognize dozens of viral proteins

The accumulation of fibrin/amyloid microclot deposits in LongCOVID, ME/CFS, & LongLyme patients may impede blood flow – preventing oxygen from reaching and perfusing tissue. Platelet activation can also lead to inflammatory signaling capable of damaging blood vessels and surrounding tissue. To potentially mitigate these issues, the project team will run a clinical trial to establish if daily use of Lumbrokinase, a fibrinolytic enzyme, is well-tolerated and associated with symptom improvement in participants. The opportunity to evaluate the similarities and differences in the three different patient groups with respect to the role of microclots and platelet hyperactivation in producing symptoms is novel, and has not been previously explored.

Lumbrokinases are a group of enzymes that were isolated and purified in Japan from the earthworm species Lumbricus rubellus. The enzymes are capable of degrading both plasminogen-rich and plasminogen-free fibrin, and are recognized as fibrinolytic agents that can be used to treat various conditions associated with thrombosis. Indeed, Lumbrokinase is widely used clinically in China as a fibrin disruption agent, and has shown therapeutic promise for use in dissolving clots, lowering whole blood viscosity, and reducing platelet aggregation/hyperactivation.