Familial lipoprotein lipase deficiency usually presents in childhood. Stigmata of the disorder is hypertrigliceridemia. Symptoms are consistent with abdominal pain, recurrent acute pancreatitis, eruptive cutaneous xanthomata and hepatosplenomegaly. Symptoms usually resolve with dietary restriction of total fat to 20 g per day or less. However, a subset of adult patients does not respond to diet and keeps developing pancreatitis.
For these patients the use of tiparvovec (Glybera) is proposed. Tiparvovec is one of the few gene therapy remedies available today. The concept is the one of a modified virus, that is made unable to replicate in human cells and in which a functioning copy of the LPL gene is inserted. By 'infecting' the muscle, the modified virus carries the correct LPL gene into cells. Cells can then start producing a functioning enzyme. Several disease-causing mutations of all kinds have been described in the LPL gene. The disease is autosomal recessively inherited and, according to the type of mutation, lipoprotein lipase activity can be absent or markedly reduced. Glybera is the first gene therapy ever recommended for approval in Europe.
The proposal for lipoprotein lipase deficiency recalls the milestones of gene therapy, an exciting field unfortunately marked by several failures. Gene therapy approaches have been so far hampered basically by problems of immunogenicity, carcinogenicity and manufacturing. After several years of stall, things are now moving again. Clinical trials are now ongoing for Leber congenital amaurosis, ß-thalassemia, chronic lymphoid leukemia, adenosine deaminase deficiency, X-linked severe combined immunodeficiency (SCID) and Wiscott-Alrdich syndrome. For an interesting review on the recent advances of gene therapy, read A Mullard.
For these patients the use of tiparvovec (Glybera) is proposed. Tiparvovec is one of the few gene therapy remedies available today. The concept is the one of a modified virus, that is made unable to replicate in human cells and in which a functioning copy of the LPL gene is inserted. By 'infecting' the muscle, the modified virus carries the correct LPL gene into cells. Cells can then start producing a functioning enzyme. Several disease-causing mutations of all kinds have been described in the LPL gene. The disease is autosomal recessively inherited and, according to the type of mutation, lipoprotein lipase activity can be absent or markedly reduced. Glybera is the first gene therapy ever recommended for approval in Europe.
The proposal for lipoprotein lipase deficiency recalls the milestones of gene therapy, an exciting field unfortunately marked by several failures. Gene therapy approaches have been so far hampered basically by problems of immunogenicity, carcinogenicity and manufacturing. After several years of stall, things are now moving again. Clinical trials are now ongoing for Leber congenital amaurosis, ß-thalassemia, chronic lymphoid leukemia, adenosine deaminase deficiency, X-linked severe combined immunodeficiency (SCID) and Wiscott-Alrdich syndrome. For an interesting review on the recent advances of gene therapy, read A Mullard.
FACTS
The LPL gene spans about 32.1 kb and includes 10 exons. It is located on 8p22.
References
Brown T, First Gene Therapy Ever Recommended for Approval in Europe, www.medscape.com.
Brunzell JD, 2011, PMID: 20301485
Mullard A, 2011, PMID: 21959273
