What is Lysosomal Storage Disorder?
Lysosomal storage disease refers to a group of more than 50 genetic diseases caused by lysosomal dysfunction. To understand lysosomal storage disease, one must first understand lysosomes and lysosomal function. Lysosomes are sacs of enzymes within cells that are involved with waste recycling. For example, the lysosomes will digest large waste molecules, and then pass them onto other parts of the cell to continue the recycling process. The magic of lysosomal function lies in its many enzymes, which are necessary for the lysosomes to process waste molecules. The enzymes contained in the lysosome sac are hydrolytic enzymes, which break down a variety of biomolecules, including: proteins, carbohydrates, fats, and other cellular debris. The lysosomal sac is equipped with more than 50 enzymes to help carry out its functions as a waste disposal system. However, in those with lysosome storage disease, lysosomal dysfunction results from an enzyme deficiency – and this often results in problems with metabolism of lipids, glycoproteins, and mucopolysaccharides. The following diseases are classified as lysosomal storage disorders:
Tay-Sachs: Tay-Sachs is a genetic disorder that leads to deterioration of nerve cells. As a result, physical and mental function also deteriorates. The disease causes the accumulation of cell membrane components called gangliosides within the brain – which causes premature death of brain cells. Although the disease is more common amongst babies and young children, there is an adult/late-onset form of the condition, although it’s often misdiagnosed. Adult-onset Tay-Sachs typically causes symptoms like difficulties with speech and swallowing, cognitive decline, and often secondary psychological conditions like schizophrenia.
Gaucher disease: Gaucher disease leads to the accumulation of molecules known as sphingolipids in various organs, including: the spleen, liver, kidneys, lungs, brain, and bone marrow. These accumulations cause painful swelling, bruising, fatigue, and often leads to enlargement of the liver and spleen. Those with Gaucher disease are deficient in an enzyme that breaks down glucoslyceramide, which leads to the accumulation of waste products.
Pompe disease: Also known as acid maltase deficiency, Pompe disease leads to damage of the muscle and nerve cells caused by accumulation of glycogen. Those with Pompe disease have a deficiency in an enzyme called alpha-glucosidase. Glycogen is normally stored in muscles as a source of available energy, but in Pompe disease, too my glycogen causes progressive muscle weakness, and the condition often affects the heart, liver, and nervous system.
How is Lysosomal Storage Disorder Treated?
Although there are no cures for any of the lysosomal storage disorders (LSD), there are some treatments available that effectively address the debilitating symptoms. LSD’s have been treated with bone marrow transplantations in the past, based on the theory that this may provide the patient with a permanent source of the defective enzyme. Although bone marrow transplants were a choice therapy for many years, subsequent studies revealed that it’s difficult to predict the outcomes, and the outcomes often depended upon the type of donor. Later studies suggested that only young children should undergo this type of therapy, which led to new and more innovative treatment strategies. Gene therapy is another suggested route, which is based on the idea of directly transferring normal genes into defective cells. In doing so, active enzymes are supplied, reducing the aggregation of waste of cellular products. Although gene therapy seems promising, researchers explain that additional studies are necessary before it becomes widely implemented. For example, it’s unsure how safe this therapy is, and at what age gene therapy is optimal. Furthermore, many researchers are cautious about possible immunologic reactions with gene transplant therapy.
Why Enzyme Therapy?
Enzyme replacement therapy has been used in all types of LSD’s, and clinical studies suggest that enzyme therapy may help to improve complications with neuropathic pain, renal issues, and myocardial and nerve fiber issues. Although enzyme therapy is often studied as injected, enzyme therapy is now effectively administrated as oral supplementation, and serves the same purposes as injected enzyme replacement therapy. While enzyme therapy is not a cure for LSD’s, it greatly attenuates the long list of symptoms caused by them. In addition, the safety and efficacy of enzyme replacement therapy is well documented in clinical trials from around the world. One of the biggest hurdles that patients often faced was the high cost of enzyme replacement therapy, however, pharmaceutical-grade enzymes are now available as over-the-counter supplements, making the treatment more affordable and accessible. Choosing systemic enzymes that have protective enteric coating ensures that the enzymes reach organs, helping to break down cellular waste products and reduce symptomology. It’s also important to note that complications previously seen in injected forms of enzyme therapy were due mainly to the injections themselves. For example, common complications involved itching and redness at the IV site, and general itching. With orally consumed enzymes, these side effects are no longer at issue.