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Case ReportOpen Access

Enzymes for Disease Treatment: A Review Volume 49- Issue 3

Girum Tefera Belachew*

  • Department of Biotechnology, College of Natural and Computational Sciences, Debre Birhan University, Ethiopia

Received: March 15, 2023;   Published: March 29, 2023

*Corresponding author: Girum Tefera Belachew, Department of Biotechnology, College of Natural and Computational Sciences, Debre Birhan University, P.O. Box 445, Debre Birhan, Ethiopia

DOI: 10.26717/BJSTR.2023.49.007809

Abstract PDF


Background Since ancient times, enzymes have been widely used in a variety of sectors. Unfortunately, until the late 1950s, when scientists finally discovered the gold mine, they were sitting on, their potential as medicines lay dormant. The use of enzyme therapy for the treatment of numerous diseases, such as lysosomal storage disorders, cancer, Alzheimer’s disease, irritable bowel syndrome, exocrine pancreatic insufficiency, and hyperuricemia, has increased significantly during the past few decades. Gene therapy, the treatment of microbial infections, and wound healing are further uses for enzymes.

Keywords: Disease; Human study; Therapeutic; Treatment


Since 6000 BC, enzymes have been unwittingly used in a wide range of industries. Even after Payen and Persoz described the first enzyme in 1833, enzymes were only employed commercially, and the majority of their potential remained untapped [1,2]. Yet, a clear image of the use of enzymes for therapeutic treatments slowly emerged with the development of better lab equipment and the separation of enzymes in pure form. We describe enzyme therapy as the use of biological globular proteins that catalyze key biochemical reactions in their natural state or when fused with particular chemicals that enhance their properties in order to cure diverse problems. According to PubMed metrics, enzyme therapy has developed into a fastexpanding subject in recent years, with more than 300 publications relating to «enzyme replacement therapy» alone published every year over the past ten years, as seen in (Figure 1).

The earliest widely known application of enzymes for medicinal purposes was in enzyme replacement therapy. Dr. Christian de Duve suggested in 1964 that enzymes might be used to treat lysosomal storage disorders [3]. Since its inception, enzyme replacement therapy has advanced significantly and is now used to treat a variety of enzyme deficiency disorders, including adenosine deaminase-severe combined immune deficiency [4], Gaucher disease [5], adenosine deaminase-fabry disease [6], Fabry disease [7], Pompe disease [8], Hunter syndrome, Hurler-Scheie syndrome [9], Sly syndrome [10], Morquio A syndrome [11], Tay-Sachs disease [12], Wolman disease [13], adenosine deaminasesevere combined immune deficiency [4], hypophosphatasia [14], metachromatic leukodystrophy [15], Sphingomyelinase deficiency [16], homocystinuria [17], Maroteaux- Lamy syndrome [18], alpha-mannosidosis [19], and ceroid lipofuscinosis type 2 [20].

The treatment of exocrine pancreatic insufficiency, which can occur in a number of disorders including cystic fibrosis, chronic pancreatitis, and celiac disease, with enzymes is known as pancreatic enzyme replacement therapy [21]. In addition, the therapeutic application of enzymes has expanded in the modern period to include gene therapy [22], the treatment of cancer [23], the healing of wounds [24], the enhancement of irritable bowel syndrome patients’ lives [25], and the prevention of antibiotic-resistant microbial infections [26]. In this post, we go through the characteristics of several enzymes and how well they work to treat certain diseases. Based on the numerous disorders that they are used to cure; the enzymes have been divided into divisions. An update on recent advancements in enzyme research and their use as medicines is also provided in this article.

Figure 1.


Medicinal Value of Enzymes

Anti-Alzheimer’s Disease: Alzheimer’s disease is a serious illness that can cause someone to vanish long before they really pass away. The development of -amyloid peptide plaques and neurofibrillary tangles in the brain, which results in the deterioration of the nervous system, is the pathological condition linked with Alzheimer’s disease. This buildup of amyloid plaques and neurofibrillary tangles causes extensive oxidative damage to neurons, which ultimately results in cell death. Dementia progresses and the cognitive system becomes severely dysfunctional as a result of neuronal loss. The proteolytic activity required to break down amyloid peptides in the brain into swiftly removed, nonneurotoxic chemicals has been found in numerous enzymes in recent years.

The term «amyloiddegrading enzymes» refers to these enzymes. Serine proteases, aspartyl proteases, cysteine proteases, and zinc metalloprotease enzymes are the several types of enzymes that have been utilized to treat Alzheimer’s disease [22]. The Neprilysin family of enzymes is one of the zinc metallopeptidase enzyme families. Neprilysin enzymes have been seen to break down hydrophobic -amyloid plaques’ N-terminal end into little peptides with fewer than fifty amino acid residues. The breakdown of these betaamyloid plaques was shown to be significantly reduced in mice whose expression of the enzyme Neprilysin was knocked off. Neprilysin, Neprilysin-2, Endothelin-Converting Enzyme-1, and Endothelin-Converting Enzyme-2 are enzymes from the Neprilysin family that have been linked to the elimination of -amyloid plaques in the brain. The insulin degrading family of zinc metallopeptidases, which differs from the Neprilysin family in terms of structure and catalytic function, has been discovered to be connected to the clearance of amyloid plaques from the brain. One of the enzymes in this family that has been proven to dissolve beta amyloid plaques is inulysin. Furthermore, it has been discovered that even these insulin degrading enzymes’ inactive form aids in the breakdown of -amyloid plaques by acting as a chaperone. It has been noted that the angiotensin-converting enzyme cleaves the more harmful -amyloid-42 to the less harmful -amyloid-40.

Moreover, it has been observed to cleave -amyloid-40 in particular locations. The mono-carboxypeptidase enzyme angiotensinconverting enzyme has been seen to cleave-amyloid-43 to produce amyloid-42. Matrix metalloproteinase-2 and matrix metalloprotease 9 have been seen to cleave neurofibrillary tangles [27] serine protease known as plajin can break down amyloid fibrils and plaques. Little amounts of an oligopeptidase enzyme termed acyl-peptide hydrolase are created by cells via a poorly understood mechanism. After the 13th, 14th, or 15th amino acid, this enzyme has been seen to break both oligomeric and monomeric -amyloid plaques. In mouse models, the cysteine protease enzyme cathepsin B has been shown to lower the concentrations of -amyloid in the brain. It has been noted that the zinc ectopeptidase enzyme glutamate carboxypeptidase breaks down amyloid plaques in the brain into amyloid-14, amyloid-18, and amyloid-35 [28].

Anti-Cancer Activity An extremely fatal terminal condition known as pancreatic carcinoma causes aberrant cell division in pancreatic cells, which results in the growth of metastatic tumors. Precancerous lesions that develop into pancreatic carcinoma can be roughly categorized as pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms, and mucinous cystic neoplasms. The type of pancreatic intraepithelial neoplastic lesions most frequently seen to develop into metastatic tumors are these. Due to their size and rapid growth into carcinomas and metastases to other tissues, these lesions are also difficult to identify and do not give enough time for therapy. A propensity for pancreaticancer has been linked to mutations in a number of genes, including KRAS, TP53, SMAD4, ATM, BRCA1, BRCA2, PALB2, PRSS1, p16/CDKN2A, MLH1, and STK11 [29].

Hepatocellular carcinoma is a highly typical metastatic malignant tumor that can result in tissue necrosis and organ failure in the liver by causing a number of clinical alterations. Hepatitis C infection, excessive alcohol consumption, and aflatoxin B1 exposure are a few of the most prevalent risk factors [30]. Melanomas are cutaneous malignant metastatic tumors with a high mortality rate that have been on the rise recently. These cancers are brought on by a confluence of hereditary and environmental factors. Exposure to ultraviolet light is one of the main causes of melanoma. Lesions on the skin that show uneven borders and changes in pigmentation and hue are indicative of melanoma. In a 1999 study, it was discovered that including proteolytic enzymes in the diet helped patients with pancreatic cancer live longer.

The study’s small sample size, however, makes it difficult to draw many conclusions [31]. Hepacid is a polyethylene glycosylated arginine deiminase enzyme that is injected intramuscularly and is being researched as a therapy for hepatocellular cancer. Another polyethylene glycosylated arginine deiminase-derived enzyme used to treat metastatic melanoma is called melanocid. Both of these enzymes break down and limit the amount of arginine, an essential amino acid required for the growth of cancerous cells [32]. Although arginine deiminase enzymes have been shown to have a considerable impact on mice, their usage in humans is still restricted due to their brief serum half-life. Furthermore, due to their microbial origin, these enzymes have been found to have a significant immunogenicity in mammals.

Despite the fact that the enzymes were seen to have a considerable impact on certain patients during clinical trials, the outcomes were incredibly uneven, and they were also seen to have a number of undesirable side effects, including higher ammonia levels. These genes, which produce the arginine deiminase enzyme, have been identified from a variety of bacteria, including Streptococcus sangria, Mycoplasma arginini, and Pseudomonas aeruginosa, and are primarily overexpressed in Escherichia coli BL21 cells [33]. The disorder known as acute lymphoblastic leukemia is brought on by the malignant transformation and proliferation of lymphoid progenitor cells. Many physical symptoms, including anemia, thrombocytopenia, weight loss, leukopenia, fever, bruising propensity, hepatosplenomegaly, and night sweats, are used to describe this illness [34].

This kind of leukemia can now be treated using the enzyme L-asparaginase. This enzyme breaks down L-asparagine into ammonia and L-aspartate, which causes cell death. Unfortunately, using this enzyme for treatment has a number of disadvantages, including toxicity and cell resistance to the enzyme. Erwinase and Oncaspar are the two enzymes that have been approved for use in the management of acute lymphoblastic leukemia. L-asparaginase is an enzyme, and oncaspar is a polyethylene glycosylated version of it. The enzyme is polyethylene glycosylated, which improves stability and plasma retention duration while lowering immunogenicity and proteolysis [35]. Acute lymphoblastic leukemia is being treated with Erwinase, a different L-asparaginase enzyme made from Erwinia chrysanthemi [36].

Antidiabetic Effect: In glucose hemostasis, the enzyme glucokinase is crucial. A protein called glucokinase regulatory protein controls its function [37]. Transcriptional factors control glucokinase activity in the pancreas, whereas glucokinase regulatory protein controls it in the liver. The first stage in the metabolism of glucose is catalyzed by the enzyme glucokinase, and mutations in this enzyme are linked to young-onset diabetes with maturity. High levels of this enzyme and enhanced glucose tolerance were caused by a high-carb diet [38].

Anti Cardiovascular Diseases: In the world, cardiovascular disease (CVD) is the leading cause of death. This severe disease is thought to be treatable by ERT. First, urokinase is an enzyme whose substrate is plasminogen, an inactive form of the serine protease plasmin. This enzyme turns plasminogen into plasmin, which sets off a proteolytic cascade that takes part in the extracellular matrix’s breakdown during thrombolysis (ECM). Many vascular disorders can be treated with the use of this procedure [39]. Second, the enzyme nattokinase promotes fibrinolytic activity by inactivating plasminogen activator inhibitor 1 [40].

Troubleshooting Enzyme Treatments: For a variety of diseases, enzymes have been employed as therapeutic medicines [41-43]. Studies on the potential of enzymes as therapeutic agents and on the metabolic pathways involved in many diseases have benefited from advancements in both biotechnology and protein engineering [44]. Recombinant enzymes have consequently become new therapeutic options for a variety of disorders, including cancer and genetic anomalies (LSD, CF, etc.) [44,45]. Enzyme treatments must overcome enzyme fast clearance in vivo, undesired off-target interactions, and patient immune response to become commonly used medications.

The most amazing therapeutic enhancement strategies to date include the encapsulation, molecular alteration, and active monitoring of immune response. Applying the enzyme medication directly to the intended tissue is one of the simplest strategies to avoid undesirable off-target reactions. Deoxyribonuclease has been administered via eye drops for individuals with dry eye illness [46] in this context, and urokinase has been delivered via catheter to dissolve intraluminal clots [47]. Other strategies, such as enzyme encapsulation and modification as well as monitoring of patients’ immune reactions, are being developed, though, to overcome the specific limitations [48-60].


Many disorders are treated with enzyme therapy. There are various stages of clinical trials for some enzymes. Pharmaceutical companies are now producing safer, less expensive enzymes with increased potency and specificity thanks to advancements in biotechnology [61-78]. Enzymes and medications have the potential to work synergistically to treat a variety of ailments and lessen the adverse effects of specific medications [79-84]. Such biochemical leads can be developed for therapeutic evaluation thanks to the high degree of specificity of enzymes and the fast-growing competence in macromolecular chemistry (Table 1).

Table 1. Enzyme therapy research as per published literature.


Data Availability

All of the required data will be available upon request to the corresponding author.

Authors’ Contributions

The author wrote the review article alone.


The author is grateful to thank those individuals who gave help directly or indirectly.

Financial Support and Sponsorship

There is no financial support and sponsorship.

Conflicts of Interest

There are no conflicts of interest.


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