Enzyme Replacement Therapy (ERT)

Enzymes (Hex-A for TSD) produced in a laboratory setting are administered to subsidize or replace the missing enzymes. This technique has proven effective in some LSDs but has not been useful to date treating LSDs with neurological involvement. The laboratory enzymes face the same problems stem cells and cord blood cells do: crossing the blood brain barrier.

This therapy maybe the simplest of all the therapies, but it is not proving effective in disease with neurological components – so far. The plan is simple – if the body has low levels of some enzymes – let's produce some and inject them into the body. Since the cells are adept at picking up enzymes from outside the body and absorbing them – it seems like it should work.

This therapy has been very effective with some lysosomal storage diseases (Gaucher disease, Fabry disease, or MP1) - but not with the disease that involve enzymes needed in the brain. The blood brain barrier is a factor, the foreign object response of the white blood cells is a factor, and the quality of enzymes needed is a factor. Additionally, ERT treats the symptoms temporarily – the injected enzymes will eventually die off.

In therapies like gene therapy the number of cells injected is lower because the cells duplicate once they arrive on site. In cord blood transplant therapies the blood continually regenerates Hex A. With a therapy like ERT- we need to put in as many as we need, and the process may need to be repeated several times – it might be able to slow the progression – but it cannot be a permanent solution (at least not yet).

Gene Therapy (GT)

- Gene Therapy (GT) is to treat Tay-Sachs and other lysosomal strorage disorders.
In this therapy, semi-infectious vector as viral vector to use by means of introducing new genetic materials into the target cells. Then the viral vector or molecular trucks to be transported one or more therapeutic genes into diseased cells in the brain. The vectors will direct the cells to produce the large amount of Hex A enzyme and this will be distributed throughout the entire cell.
- By this way, the storage of lysosomal in the brain will gradually reduce. (it helps to reduce the accumulation of lysosomal in the affected area.

Substrate Reduction Therapy (SRT)

- SRT represents a novel approach for treatment of lysosomal storage disorders.
- The another stragey for the lysosomal strorage disease is substrate reduction therapy. It was first pioneered in the laboratory by Norman Radin and this research has now been introduced into the clinical trials. The other experimental research for SRT by using altenate enzymes to reduce the accumulation of substrate with the increase the catabolism of GM2 ganglioside in the brain.
- The another experiment also using the enzyme called sialidase which can effectively bypassed the genetic defect and the GM2 gangliosides to be metabolized. In this way, the substrate levels becomes inconsiderable as negligible.
- The another metabolic therapy is under investigation to use miglustat, a drug or a glucosylceramide synthase inhibitor. It works by inhibiting glucosylceramide synthase (the enzyme that forms glucosylceramide, which accumulates within the macrophages).
- This drug is a reversible inhibitors of the enzyme glucosylceramide synthase. The first step of catalyze in synthesisizing of glucose-based glycosphingolipids like GM2 ganlioside.

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