Drug development based on long-term clinical and basic research

Continuous blood flow in veins is crucial to life. If a wound appears in the wall of a blood vessel, platelets rush to rescue. They attach to the wall of the damaged vessel and to each other, forming a local clot. This is how they repair the damage to the blood vessel. Balanced blood coagulation, or hemostasis, is the body's own mechanism for protecting life. 

Many diseases, hereditary factors or even invasive vascular procedures can cause excessive clotting of blood, or obstructions, in veins or arteries. The most fatal consequences of a blood clot include pulmonary embolism, myocardial infarction and a stroke.

The body's own substances help to regulate coagulation

The mast cells in the human body produce heparin, which is an anticoagulant that prevents excessive clotting of blood. 

"Heparin, which is isolated from the pig's intestinal mucosa, is a necessary drug in the prevention of vascular occlusions in situations like vascular surgery and the treatment of coagulation disorders,” says Riitta Lassila, Head Physician at HUS and the University of Helsinki, who has studied the mechanism of coagulation for a long time.

Lassila already became interested in molecules that affect blood clotting at the beginning of her medical studies. 

“I wanted to understand how in a massive piping system like our circulatory system, the blood suddenly does not flow as it should. What is it that causes this and what can we do about it?” Lassila says.

In 1997, Lassila's research group paid attention to a molecule that occurred naturally in the human body and appeared to be governing the clotting of blood. This molecule contributed to the recovery of the damaged area in the blood vessel (i.e. hemostasis), but simultaneously calmed down excessive interaction between platelets (i.e. thrombocytes) and the von Willebrand factor and other coagulation factors, thus preventing the coagulation of blood outside the damaged area. 

The development of a drug is a journey of discovery lasting a couple of decades

Lassila and her group prepared a drug that imitated the human body’s own substance by combining two molecules: heparin and albumin. 

“With a grant from the Research Council of Finland, we managed to first develop the manufacturing technology for the drug together with a Dutch top expert and a Swiss pharmaceutical manufacturer. In 2009, a pharmaceutical company called Aplagon was established to develop this academic discovery towards a drug that would be commercialised. After several rounds of funding, we have now proceeded to the clinical phase and have applied to the EU medicines authorities for a licence to use the APAC drug in hospital treatment,” Lassila explains.

The discoveries made in the research work have only increased her curiosity, and the expensive multiphase drug trials and the related bureaucracy have not been able to make it fade.

Reaching the research phase in which the drug can be studied in patients has been laborious, expensive and slow for the researchers. Lassila is now hopeful because no other medicine in the world has proved to be safe and effective in maintaining the vascular access required in dialysis when tested in preliminary clinical trials. 

Vascular access required by kidney patients becomes easily blocked

In dialysis, minor vascular surgery is performed on a blood vessel in the arm to create a vascular access that makes it possible to clean the blood using the dialysis machine. During the treatment, two routes to the machine are used. One of them brings the blood to the machine to be cleaned and the other one returns the cleaned blood back to the patient’s body. 

“This vascular access becomes blocked easily and never matures and becomes functional. A non-mature vascular access slows down the start of the dialysis and causes high costs. A blocked vascular access causes additional work, is time-consuming for the patient and increases the risk of infection. The vascular access also makes patients more prone to thrombosis, which may lead to death,” Lassila explains. 

The aim is also to trial the drug in calming down blood vessel damage that obstructs arteries. For example, persons with diabetes have these especially in their peripheral circulation.

HUS’s support to pharmaceutical research opens up many opportunities

In autumn 2023, HUS set up support funding targeted at pharmaceutical research. This support funding includes continuous education in conducting pharmaceutical research, among others. HUS’s support to pharmaceutical research has speeded up the work and made international training and months of paid leave as a researcher possible to specialist Eeva-Maija Weselius, the member specialized in vascular access surgery in the research group.

“If everything goes well, in a few years’ time we may have a new medicine available to specialists in vascular access surgery to keep the vascular access open and functional. This would benefit both the kidney disease patients at HUS and the entire HUS,” says Lassila. 

International research cooperation has also provided evidence of other possible indications for the APAC drug molecule. 

“We have several hereditary, lifestyle-induced and sudden inflammatory diseases involving vascular occlusions, the progress of which can hopefully be safely slowed down and treated with this medicine," says Lassila.