Enzyme Replacement Therapy For Lysosomal Storage Disorders

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Lysosomes are a component of the cells in your body. Their job is to act as a “clean up crew” and dispose of waste such as old or damaged cells and cell parts. They also act as part of the body's defence against pathogens like bacteria and viruses.1

Lysosomal storage disorders (LSDs) are a type of rare genetic disorder, they prevent the clean-up process from happening properly and this causes unwanted materials to stay behind and build up, which affects the function of normal cells.2

Lysosomes are like bags, and they are full of different enzymes, the type of enzyme which is lacking is dependent on the specific type of LSD you have, there are more than 70 types of LSDs, here are some examples:

However, enzyme replacement therapy (ERT) may be a way to help increase the lack of the specific enzyme and help to improve quality of life.3

The impact of LSDs on patients

Areas of the body affected and outcomes of the LSD may vary depending on which type you have. However, some symptoms you may face can include:

  • Difficulties in motor skills
  • Developmental delays
  • Cognitive impairments 
  • Sometimes a shortened lifespan

Currently, there is no cure for LSDs, nevertheless, there are treatments to help manage the symptoms and improve your quality of life.2

The role of genetics

LSDs are caused by genetic mutations within genes that hold the instructions needed for cellular clean-up. This causes the clean-up process to go wrong.2

Usually, two copies of the mutation are required for the disorder to manifest, one from each parent. Genetic counselling is available to prospective parents, so they can undergo genetic testing to make an informed decision. Early diagnosis is also important if LSD is suspected so that symptoms can be managed.4

Research is also ongoing to gain further insight into the genetic mechanisms underpinning LSDs, this will allow for the development of better treatments, which may be available to you and your family in the future.4

What is enzyme replacement therapy?

As the cause of LSDs is a lack of a specific enzyme, ERT directly treats the root cause of the symptoms by supplementing the enzymes that aren't functioning or are reduced. 2,14 Early intervention is very important, as whilst this medicine can improve quality of life, it may not be able to reverse any already occurred damage.5

Diseases that enzyme replacement therapy can treat

Gaucher's disease

If you have Gaucher’s disease the enzyme you are deficient in is glucocerebrosidase this enzyme usually breaks down glucocerebroside. ERT involves intravenous supplementation of glucocerebrosidase that you will receive for the rest of your life, the frequency and dosage of which will be tailored to your individual case, taking into account the severity of the disease and response to treatment.6 

This treatment can lead to a reduction in symptoms like:

However, it will not slow or prevent neurological symptoms if you have them. It is important to remember that this treatment will not cure Gaucher’s disease and will only help manage the symptoms; and the effectiveness of treatment will vary depending on the individual. 15 The type of Gaucher’s disease you have is also important. Generally, type 1 responds best, while type 2 does not tend to respond to ERT. 7

Fabry disease

Fabry disease is caused by a deficiency in the alpha-galactosidase A (AGA) enzyme, an enzyme which normally breaks down globotriaosylceramide (Gb3). Therefore AGA deficiency will cause a Gb3 to accumulate.5 

Gb3 build-up can cause:

  • Skin abnormalities
  • Problems with your heart
  • Dysfunction in the kidneys4

ERT for Fabry disease is given in the form of intravenous synthetic AGA, this AGA functions in a similar way to the natural form and is able to break down Gb3 improving symptoms.6


Mucopolysaccharidosis (MPS) includes a group of LSDs in which glycosaminoglycans (GAGs) accumulate due to a deficiency in an enzyme. The specific enzyme is dependent on the type of MPS you have. GAGs play an important role in the connective tissues, however, when they build up they can cause problems in the:

  • Bones 
  • Joints
  • Heart
  • Hearing 
  • Vision 
  • Cognition

ERT has varying results and is dependent largely on the type of MPS that you have.7 In MPS I (Hurler, Hurler-Scheie, and Scheie syndromes), MPS II (Hunter syndrome), MPS IV (Morquio syndrome), MPS VI (Maroteaux-Lamy syndrome) and MPS VII (Sly syndrome).

ERT has been shown to help alleviate symptoms that aren't neurological.  However, there aren't approved therapies for MPS III (Sanfilippo syndrome) but there are clinical trials being done presently.8

Pompe disease (glycogen storage disease type II)

If you have Pompe disease there is a lack of the enzyme acid alpha-glucosidase (GAA) in your body or this enzyme is not functioning as it should. This enzyme normally breaks down glycogen (a storage molecule made up of glucose)  into glucose, however, when this enzyme is lacking this can cause glycogen to pile up and cause problems such as muscle weakness and heart problems.9

A synthetic version of this enzyme can be made and injected into the vein, this can help to reduce some of the symptoms, especially those in muscles like the heart, and slow down disease progression. However, this will usually have to be administered at regular intervals.9

Diseases such as Niemann-Pick disease, Tay-Sachs disease and Metachromatic leukodystrophy (MLD) are not generally treated using ERT, though research trials are being performed currently so this may change.9

The advantages of enzyme replacement therapy

  • It reduces the build-up of unwanted material: ERT replaces the enzyme that is lacking or not working and this breaks down the substance that has built up;  In this way, ERT can reduce the accumulated substance and thus reduce the speed of progression.2
  • It reduces clinical symptoms: depending on the type of LSD, ERT can reduce troublesome symptoms that might be associated with your disease such as abnormalities in the bones and enlarged organs (organomegaly).3
  • It's not invasive: the intravenous administration means ERT is a less invasive option than some other treatments available for LSDs.4

The disadvantages of enzyme replacement therapy

  • It might have trouble penetrating some tissues: for ERT to work the enzyme must be able to access the affected cells and tissues, but the enzyme may not be able to penetrate some tissues as easily as others, particularly the central nervous system (brain and spinal cord); This may have an effect on the ability of the ERT to address neurological symptoms, meaning that ERT cannot treat some LSDs currently4
  • Can be expensive: ERT tends to carry a high cost which may limit access for some patients.5
  • Your body may attack the medicine: Some patients' immune systems may produce antibodies against the enzyme in the treatment, which can decrease the efficacy of the treatment over time.4
  • Diagnosis can be difficult: ERT is more beneficial when you begin it early in the course of your disease, however, people with LSDs may be misdiagnosed due to the rarity of the illness, as such patients may not get their diagnosis until late in their progression4
  • It might not be able to reverse all the damage: ERT has been shown to improve some symptoms and slow progression, however, it may not be able to reverse the damage that has already occurred.2

Looking to the future

Advancement in enzyme replacement therapy

The ability of enzymes to reach the affected cells and tissues, (especially those in the central nervous system) can be improved using special carriers called nanoparticles and liposomes. This suggests that ERT could treat neurological symptoms of LSDs like cognitive decline in the future.10

Moreover, enzymes are being designed to be more stable so they don’t degrade as quickly and can be effective in the body for longer. Additionally, new enhanced enzymes are being developed that do a better job of breaking down the accumulated substances so they require lower doses.10

In the future, a personalised approach (precision medicine) may be used, tailoring ERT to the specific gene mutation which may increase the number of subtypes that can be treated.10

Investigating ways to correct faulty genes

Using technologies like CRISPR-Cas9 (a tool scientists use to change DNA sequences), to correct gene mutations allows the cell to make a working version of an enzyme that is lacking or faulty, thus treating the root cause of LSD’s.11

Stem cells can differentiate and replace damaged cells and may be used with gene therapy as these cells can continue to produce the desired enzyme in the patient.11


  • Enzyme replacement therapy (ERT) can help to treat lysosomal storage disorders (LSDs), a type of disorder where lacking or faulty enzymes leads to a buildup of substances in the body
  • ERT can alleviate symptoms by replacing deficient or faulty enzymes
  • Examples of treatable LSDs include Gaucher’s disease, Fabry disease, some types of Mucopolysaccharidoses and Pompe disease
  • Advantages of ERT include: breaking down unwanted substances, reducing clinical symptoms and being a relatively non-invasive treatment
  • Disadvantages include issues with enzymes reaching the affected cells, high cost, immune response to ERT and that it is less effective if you take it later in the disease progression
  • In the future ERT involving more efficient enzymes, more personalised approaches and technologies aimed at correcting faulty genes may be available


  1. De Duve C. Lysosomes revisited. European Journal of Biochemistry [Internet]. 1983 Dec [cited 2024 Jan 10];137(3):391–7. Available from: https://febs.onlinelibrary.wiley.com/doi/10.1111/j.1432-1033.1983.tb07841.x
  2. Sun A. Lysosomal storage disease overview. Ann Transl Med [Internet]. 2018 Dec [cited 2024 Jan 10];6(24):476. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331358/
  3. Beerepoot S, Nierkens S, Boelens JJ, Lindemans C, Bugiani M, Wolf NI. Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective. Orphanet J Rare Dis [Internet]. 2019 Nov 4 [cited 2024 Jan 11];14:240. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829806/
  4. Enzyme replacement therapy. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012 [cited 2024 Jan 11]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK548796/
  5. Rajkumar V, Dumpa V. Lysosomal storage disease. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2024 Jan 11]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK563270/
  6. Alkhzouz C, Miclea D, Bucerzan S, Lazea C, Nascu I, Sido PG. Early clinical signs in lysosomal diseases. Med Pharm Rep [Internet]. 2021 Aug [cited 2024 Jan 11];94(Suppl No 1):S43–6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411815/
  7. Pinto e Vairo F, Rojas Málaga D, Kubaski F, Fischinger Moura de Souza C, de Oliveira Poswar F, Baldo G, et al. Precision medicine for lysosomal disorders. Biomolecules [Internet]. 2020 Jul 26 [cited 2024 Jan 11];10(8):1110. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463721/
  8. Schaible P. Modifying enzyme replacement therapy – A perspective. J Cell Mol Med [Internet]. 2022 Dec 25 [cited 2024 Jan 11];27(2):165–73. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9843529/
  9. Hughes DA, Pastores GM. Gaucher disease. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993 [cited 2024 Jan 11]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1269/
  10. Ezgu F, Alpsoy E, Bicik Bahcebasi Z, Kasapcopur O, Palamar M, Onay H, et al. Expert opinion on the recognition, diagnosis and management of children and adults with Fabry disease: a multidisciplinary Turkey perspective. Orphanet Journal of Rare Diseases [Internet]. 2022 Mar 2 [cited 2024 Jan 11];17(1):90. Available from: https://doi.org/10.1186/s13023-022-02215-x
  11. Kok K, Zwiers KC, Boot RG, Overkleeft HS, Aerts JMFG, Artola M. Fabry disease: molecular basis, pathophysiology, diagnostics and potential therapeutic directions. Biomolecules [Internet]. 2021 Feb 12 [cited 2024 Jan 11];11(2):271. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918333/

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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