Enzyme Therapy: Current Challenges and Future Perspectives

Abstract

In recent years, enzymes have risen as promising therapeutic tools for different pathologies, from metabolic deficiencies, such as fibrosis conditions, ocular pathologies or joint problems, to cancer or cardiovascular diseases. Treatments based on the catalytic activity of enzymes are able to convert a wide range of target molecules to restore the correct physiological metabolism. These treatments present several advantages compared to established therapeutic approaches thanks to their affinity and specificity properties. However, enzymes present some challenges, such as short in vivo half-life, lack of targeted action and, in particular, patient immune system reaction against the enzyme. For this reason, it is important to monitor serum immune response during treatment. This can be achieved by conventional techniques (ELISA) but also by new promising tools such as microarrays. These assays have gained popularity due to their high-throughput analysis capacity, their simplicity, and their potential to monitor the immune response of patients during enzyme therapies. In this growing field, research is still ongoing to solve current health problems such as COVID-19. Currently, promising therapeutic alternatives using the angiotensin-converting enzyme 2 (ACE2) are being studied to treat COVID-19.

Liposomes as Tools to Improve Therapeutic Enzyme Performance

“…Due to the unique and extraordinary attributes of enzymes and the broad range of targets and possible action in the living organisms, they can present multiple applications for different pathologies. They range from mild digestive disorders to serious diseases such as cystic fibrosis, metabolic and cardiac disorders, inflammatory diseases and cancers, among others [ 8 , 12 ]. According to Drug Bank online [ 25 ] more than 100 enzymes evidencing therapeutic activity and acting by different mechanisms were identified.…”

“…According to Drug Bank online [ 25 ] more than 100 enzymes evidencing therapeutic activity and acting by different mechanisms were identified. The purpose of the present work is not intended to be exhaustive in the nomination of therapeutic enzymes, as they can be found in recent revision publications [ 9 , 12 ].…”

“…Table 2 lists some of the commercialized enzyme-based drugs. In view of the high number of enzymes identified as potential useful drugs and those already approved by the FDA and/or European Medicines Agency (EMA), it is difficult to understand the correlation with the low number of enzyme formulations that reached the market [ 12 , 27 ].…”

“…One of the reasons for that discrepancy is probably related to problems arising from the behavior of exogenous enzymes when administered in living organisms. In some cases, it can result in mild or even acute allergic reactions, including anaphylaxis and death [ 1 , 8 , 12 ]. Moreover, enzymes can be degraded during circulation in the organisms, with obvious loss of activity leading to a frequent administration regimen, and may present difficulties to reach the target sites, with increasing side effects.…”

“…The therapeutic potential of enzymes is very high, ranging from metabolic and inflammatory disorders, cardiac problems to even cancer [ 8 , 11 ]. The wide range of applications and the availability of enzymes with pharmaceutical characteristics justifies the rapidly emerging increase in the market mainly since 1987, after the first approval by the Food and Drug Administration (FDA) of recombinant tissue plasminogen activator, Alteplase, for the treatment of acute ischemic stroke [ 12 ]. However, irrespective of the enormous advantages of enzymes of high specificity and selectivity to the substrate, high activity and production facilities, their application for therapeutic purposes have been limited by several drawbacks, such as immunogenic reactions, low residence time in living organisms, rapid metabolization and/or degradation and loss of activity on storage.…”