Biology Behind: Lysosome Storage Disorders!

Hello, all you lovely Science lovers! 

Do you love the new blog as much as I do? New Year and a brand New Blog all for you, my faithful readers. As I have not said it officially yet HAPPY NEW YEAR! I will not keep you waiting let's head straight into it. 

1 in 5,000 newborns will have an enlarged liver and spleen. The cruel reality of the diagnosis becomes clear, this newborn has one of the 50 conditions known as Lysosomal Storage Disorders (LSDs). LSDs are relatively rare genetic disorders, carrying a life sentence filled with complications for the body's respiratory system, skeletal system and Central Nervous System. Rare as they are, certain forms of LSDs will lead to some Children not living to see their 5th Birthday. There is no cure. Initially, the only options of treatment were blood transfusions and very risky bone marrow transplants, researchers are now focusing on treatments that tackle the source of this disorder.  

Before we begin our journey we must first familiarise ourselves with the organelle at the heart of these disorders: the Lysosome. Lysosomes are small spherical structures found in the majority of animal cells, in spite of their size they play a significant role in cellular recycling and the overall maintenance of the cellular activity. They contain digestive enzymes that are able to ‘digest’ external biological substances (such as bacteria) and recycle components from formerly defective proteins as well as other compartments of the cell.  

Based on how essential lysosomes are in the upkeep of a functioning cell they have caught the attention from the medical field. For years clinicians have been activating autophagy (where molecules and other defective organelles are taken to the lysosome for digestion) with a chemical known as TFEB. This chemical leads to the production of more cellular lysosomes and stimulation of autophagy, such responses show potential in the treatment of Parkinson's disease, cancer,  obesity and even the removal of certain pathogens (bacteria and parasites).

What leads to the onset of LSD? It all starts with a substrate (a molecule that binds to an enzyme) as an example let’s focus on Gaucher's disease (most common LSD). The onset of this disease begins when a fatty substrate known as Glucocerebroside is manufactured in the cell, once this substrate has fulfilled its destiny within the cell it begins to make its way to its final destination - the lysosome to be degraded and recycled for future use.  

However, this all depends on whether the enzyme Glucocerebrosidase is present. In the absence of this enzyme, the substrate Glucocerebroside begins to accumulate and as we know too much of one thing is never too good. This accumulation of the substrate eventually reaches toxic levels, thereby triggering the onset of the characteristic symptoms of Gaucher's disease. If you're wondering why Glucocerebroside cannot be degraded by any of the countless other enzymes present in the lysosome, the answer would be the ‘intimate’ relationship between an enzyme and its substrate.

The image below summarises how enzymes actually work in the body, similar to a lock and a key, one enzyme fits one substrate (on most occasions anyway).

All 50 LSD’s share similar developments, the only thing changing would be the substrate and the enzyme involved.

There is no cure for LSD, however, there are now several possible treatment options. For this post we are going to focus on two that aim to reduce the levels of substrate accumulation:


Perhaps after reading how LSDs develop you may have reached an assumption that a possible treatment would be to replenish lysosomes with missing enzymes or replace defective enzymes with a functional version. If so… you have just described Enzyme-replacement therapy!

This treatment option have shown to be effective in reducing spleen and liver size, alleviating anaemia ( deficiency of red blood cells or haemoglobin) and thrombocytopenia (a deficiency in platelet numbers).However, this therapies success is limited due to its inability to distribute itself to several other body parts triggering Osteonecrosis, Osteopenia and Pulmonary Hypertension. Nonetheless, the greatest shortfall would be the inability to pass the blood-brain barrier providing little relief of neuropathological symptoms.


This is where Substrate reduction therapy comes in. This treatment option does not attempt to replace enzymes, instead, it seeks to interrupt the synthesis of the substrate in the first place. This therapy is favourable to some as it is given orally and rarely triggers an immune response. Interestingly, this therapy works similarly to statins, these are prescribed to patients to lower their blood cholesterol by inhibiting the enzyme responsible for producing the cholesterol.  

Substrate reduction therapy uses a group of molecules known as imino sugars. Imino sugars work by inhibiting the enzyme responsible for synthesising the substrate. Additionally, the molecules used in this form of treatment may be small enough to penetrate the blood-brain barrier offering relief where Enzyme-replacement therapy could not. Side effects remain to be a slight problem with tremors and fevers being among them.


I really enjoy the research stage for each of my posts mainly because I love learning about aspects of Biology I have not come across before. Out of everything that I read for this post I found the overlap between LSDs neurological symptoms and other neurodegenerative diseases fascinating. There is a form of LSD called Niemann - Pick type C that is also termed Childhood Alzheimer's based on the similarities in pathology and symptoms.  Both have triggers routed in the accumulation of cholesterol in the neurones of the brain.

Sadly, the life expectancy for patients with this form of LSD is 20 years old. What fascinates me is that LSDs are rare but there should be so much more research into these disorders. They offer a rare opportunity to look at neurodegenerative disorders differently and perhaps reach new forms of treatment.

That bring us to the end of this post! I hope you have enjoyed it and more importantly that you have gained a little bit of new information on these relatively rare genetic diseases. Have an amazing week guys the aim it to have a new post on this blog every Friday or Saturday. Stay safe from this freezing weather until next time.

Science in the City

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