From Mutation Identification to Therapy: Discovery and Origins of the First Approved Gene Therapy in the Western World

Abstract

Get full access to this article

View all access options for this article.

References

Bergeron

, Normand

, Bharucha

et al. 1992. Prevalence, geographical distribution and genealogical investigations of mutation 188 of lipoprotein lipase gene in the French Canadian population of Quebec. Clin. Genet., 41:206–210.

Bijvoet

S.M.

, Bruin

, Tuzgöl

et al. 1994. Homozygosity for a mutation in the lipoprotein lipase gene (Gly139→Ser) causes chylomicronaemia in a boy of Spanish descent. Hum. Genet., 93:339–343.

Bijvoet

, Gagne

S.E.

, Moorjani

et al. 1996a. Alterations in plasma lipoproteins and apolipoproteins before the age of 40 in heterozygotes for lipoprotein lipase deficiency. J. Lipid Res., 37:640–650.

Bijvoet

S.M.

, Wiebusch

, Ma

et al. 1996b. Compound heterozygosity for a known and a novel defect in the lipoprotein lipase gene (Asp250→Asn; Ser251→Cys) resulting in lipoprotein lipase (LPL) deficiency. Neth. J. Med., 49:189–195.

Blaese

R.M.

, Culver

K.W.

, Miller

A.D.

et al. 1995. T lymphocyte-directed gene therapy for ADA-SCID: initial trial results after 4 years. Science, 270:475–480.

Bruin

, Kastelein

J.J.

, van Diermen

D.E.

et al. 1992. A missense mutation Pro157 Arg in lipoprotein lipase (LPLNijmegen) resulting in loss of catalytic activity. Eur. J. Biochem., 208:267–272.

Bruin

, Tuzgöl

, Mulder

W.J.

et al. 1994. A compound heterozygote for lipoprotein lipase deficiency, Val69→Leu and Gly188→Glu: correlation between in vitro LPL activity and clinical expression. J. Lipid Res., 35:438–445.

Brunzell

, Deeb

2000. Familial lipoprotein lipase deficiency, ApoCII deficiency, and hepatic lipase deficiency. The Metabolic and Molecular Bases of Inherited Disease, 8 ^th. Sciver

, Beaudet

, Sly

, Vale

. McGraw-Hill Inc.: New York, NY, 2789–2816.

Carpentier

A.C.

, Frisch

, Labbé

S.M.

et al. 2012. Effect of alipogene tiparvovec (AAV1-LPL(S447X)) on postprandial chylomicron metabolism in lipoprotein lipase-deficient patients. J. Clin. Endocrinol. Metab., 97:1635–1644.

10.

Devlin

R.H.

, Deeb

, Brunzell

, Hayden

M.R.

1990. Partial gene duplication involving exon-Alu interchange results in lipoprotein lipase deficiency. Am. J. Hum. Genet., 46:112–119.

11.

Dionne

, Gagne

, Julien

et al. 1992. Genetic epidemiology of lipoprotein lipase deficiency in Saguenay-Lac-St-Jean (Québec, Canada) Ann. Genet., 35:89–92.

12.

Ewald

, Hardt

P.D.

, Kloer

H.-U.

2009. Severe hypertriglyceridemia and pancreatitis: presentation and management. Curr. Opin. Lipidol., 20:497–504.

13.

Excoffon

K.J.

, Liu

, Miao

et al. 1997. Correction of hypertriglyceridemia and impaired fat tolerance in lipoprotein lipase-deficient mice by adenovirus-mediated expression of human lipoprotein lipase. Arterioscler. Thromb. Vasc. Biol., 17:2532–2539.

14.

Foubert

, Bruin

, De Gennes

J.L.

et al. 1997a. A single Ser259Arg mutation in the gene for lipoprotein lipase causes chylomicronemia in Moroccans of Berber ancestry. Hum. Mutat., 10:179–185.

15.

Foubert

, De Gennes

J.L.

, Lagarde

J.P.

et al. 1997b. Assessment of French patients with LPL deficiency for French Canadian mutations. J. Med. Genet., 34:672–675.

16.

Friedmann

, Roblin

1972. Gene therapy for human genetic disease? Science, 175:949–955.

17.

Gagne

S.E.

, Larson

M.G.

, Pimstone

S.N.

et al. 1999. A common truncation variant of lipoprotein lipase (Ser447×) confers protection against coronary heart disease: the Framingham Offspring Study. Clin. Genet., 55:450–454.

18.

Galton

D.J.

, Mattu

, Needham

E.W.

, Cavanna

1996. Identification of putative beneficial mutations for lipid transport. Z. Gastroenterol., 34:56–58.

19.

Gao

G.P.

, Alvira

M.R.

, Wang

et al. 2002. Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc. Natl. Acad. Sci. U. S. A., 99:11854–11859.

20.

Gaudet

, Méthot

, Kastelein

2012a. Gene therapy for lipoprotein lipase deficiency. Curr. Opin. Lipidol., 23:310–320.

21.

Gaudet

, Méthot

, Déry

et al. 2012b. Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPL(S447X)) gene therapy for lipoprotein lipase deficiency: an open-label trial. Gene Ther., 20:361–369.

22.

Ginzinger

D.G.

, Lewis

M.E.

, Ma

et al. 1996. A mutation in the lipoprotein lipase gene is the molecular basis of chylomicronemia in a colony of domestic cats. J. Clin. Invest., 97:1257–1266.

23.

Goldberg

I.J.

, Merkel

2001. Lipoprotein lipase: physiology, biochemistry, and molecular biology. Front. Biosci., 6:D388–D405.

24.

Groenemeijer

B.E.

, Hallman

M.D.

, Reymer

P.W.

et al. 1997. Genetic variant showing a positive interaction with beta-blocking agents with a beneficial influence on lipoprotein lipase activity, HDL cholesterol, and triglyceride levels in coronary artery disease patients. The Ser447-stop substitution in the lipoprotein lipase gene. REGRESS Study Group. Circulation, 95:2628–2635.

25.

Hata

, Robertson

, Emi

, Lalouel

J.M.

1990. Direct detection and automated sequencing of individual alleles after electrophoretic strand separation: identification of a common nonsense mutation in exon 9 of the human lipoprotein lipase gene. Nucleic Acids Res., 18:5407–5411.

26.

Henderson

H.E.

, Devlin

, Peterson

et al. 1990. Frameshift mutation in exon 3 of the lipoprotein lipase gene causes a premature stop codon and lipoprotein lipase deficiency. Mol. Biol. Med., 7:511–517.

27.

Henderson

H.E.

, Hassan

, Berger

G.M.

, Hayden

M.R.

1992. The lipoprotein lipase Gly188→Glu mutation in South Africans of Indian descent: evidence suggesting common origins and an increased frequency. J. Med. Genet., 29:119–122.

28.

Henderson

, Leisegang

, Hassan

et al. 1998a. A novel Glu421Lys substitution in the lipoprotein lipase gene in pregnancy-induced hypertriglyceridemic pancreatitis. Clin. Chim. Acta, 269:1–12.

29.

Henderson

H.E.

, Bijvoet

S.M.

, Mannens

M.A.

et al. 1998b. Ile225Thr loop mutation in the lipoprotein lipase (LPL) gene is a de novo event. Am. J. Med. Genet., 78:313–316.

30.

Henderson

H.E.

, Kastelein

J.J.

, Zwinderman

A.H.

et al. 1999. Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins. J. Lipid Res., 40:735–743.

31.

Jemaa

, Fumeron

, Poirier

et al. 1995. Lipoprotein lipase gene polymorphisms: associations with myocardial infarction and lipoprotein levels, the ECTIM study. Etude Cas Temoin sur l'Infarctus du Myocarde. J. Lipid Res., 36:2141–2146.

32.

Jukema

J.W.

, van Boven

A.J.

, Groenemeijer

et al. 1996. The Asp9 Asn mutation in the lipoprotein lipase gene is associated with increased progression of coronary atherosclerosis. REGRESS Study Group, Interuniversity Cardiology Institute, Utrecht, The Netherlands. Regression Growth Evaluation Statin Study. Circulation, 94:1913–1918.

33.

Kastelein

J.J.

, Groenemeyer

B.E.

, Hallman

D.M.

et al. 1998. The Asn9 variant of lipoprotein lipase is associated with the -93G promoter mutation and an increased risk of coronary artery disease. The Regress Study Group. Clin. Genet., 53:27–33.

34.

Keeler

C.E.

1947. Gene therapy. J. Hered., 38:294–298.

35.

Kuivenhoven

J.A.

, Groenemeyer

B.E.

, Boer

J.M.

et al. 1997. Ser447stop mutation in lipoprotein lipase is associated with elevated HDL cholesterol levels in normolipidemic males. Arterioscler. Thromb. Vasc. Biol., 17:595–599.

36.

Langlois

, Deeb

, Brunzell

J.D.

et al. 1989. A major insertion accounts for a significant proportion of mutations underlying human lipoprotein lipase deficiency. Proc. Natl. Acad. Sci. U. S. A., 86:948–952.

37.

Levy

, Deckelbaum

R.J.

, Thibault

R.L.

et al. 1990. In vitro remodelling of plasma lipoproteins in whole plasma by lipoprotein lipase in primary and secondary hypertriglyceridaemia. Eur. J. Clin. Invest., 20:422–431.

38.

Lewis

M.E.

, Forsythe

I.J.

, Marth

J.D.

et al. 1995. Retroviral-mediated gene transfer and expression of human lipoprotein lipase in somatic cells. Hum. Gene Ther., 6:853–863.

39.

Liu

, Olivecrona

1992. Synthesis and transport of lipoprotein lipase in perfused guinea pig hearts. Am. J. Physiol., 263:H438–H446.

40.

Liu

, Bengtsson-Olivecrona

, Olivecrona

1993. Assembly of lipoprotein lipase in perfused guinea-pig hearts. Biochem. J., 292,(Pt 1):277–282.

41.

Liu

, Excoffon

K.J.

, Benoit

et al. 1997. Efficient adenovirus-mediated ectopic gene expression of human lipoprotein lipase in human hepatic (HepG2) cells. Hum. Gene Ther., 8:205–214.

42.

Liu

, Ashbourne

E.K.J.

, Wilson

J.E.

et al. 2000. Phenotypic correction of feline lipoprotein lipase deficiency by adenoviral gene transfer. Hum. Gene Ther., 11:21–32.

43.

Y.H.

, Bruin

, Tuzgöl

et al. 1992. Two naturally occurring mutations at the first and second bases of codon aspartic acid 156 in the proposed catalytic triad of human lipoprotein lipase. In vivo evidence that aspartic acid 156 is essential for catalysis. J. Biol. Chem., 267:1918–1923.

44.

, Liu

M.S.

, Ginzinger

et al. 1993. Gene-environment interaction in the conversion of a mild-to-severe phenotype in a patient homozygous for a Ser172→Cys mutation in the lipoprotein lipase gene. J. Clin. Invest., 91:1953–1958.

45.

Marcil

, Boucher

, Gagne

et al. 1996. Lack of association of the apolipoprotein A-I-C-III-A-IV gene XmnI and SstI polymorphisms and of the lipoprotein lipase gene mutations in familial combined hyperlipoproteinemia in French Canadian subjects. J. Lipid Res., 37:309–319.

46.

Monsalve

M.V.

, Henderson

, Roederer

et al. 1990. A missense mutation at codon 188 of the human lipoprotein lipase gene is a frequent cause of lipoprotein lipase deficiency in persons of different ancestries. J. Clin. Invest., 86:728–734.

47.

Moran

2012. First gene therapy approved. Nat. Biotechnol., 30:1153.

48.

Nierman

M.C.

, Prinsen

B.H.

, Rip

et al. 2005. Enhanced conversion of triglyceride-rich lipoproteins and increased low-density lipoprotein removal in LPLS447X carriers. Arterioscler. Thromb. Vasc. Biol., 25:2410–2415.

49.

Normand

, Bergeron

, Fernandez-Margallo

et al. 1992. Geographic distribution and genealogy of mutation 207 of the lipoprotein lipase gene in the French Canadian population of Quebec. Hum. Genet., 89:671–675.

50.

Peritz

L.N.

, Brunzell

J.D.

, Harvey-Clarke

et al. 1990. Characterization of a lipoprotein lipase class III type defect in hypertriglyceridemic cats. Clin. Invest. Med., 13:259–263.

51.

Pimstone

S.N.

, Gagne

S.E.

, Gagne

et al. 1995. Mutations in the gene for lipoprotein lipase. A cause for low HDL cholesterol levels in individuals heterozygous for familial hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol., 15:1704–1712.

52.

Pimstone

S.N.

, Clee

S.M.

, Gagne

S.E.

et al. 1996. A frequently occurring mutation in the lipoprotein lipase gene (Asn291Ser) results in altered postprandial chylomicron triglyceride and retinyl palmitate response in normolipidemic carriers. J. Lipid Res., 37:1675–1684.

53.

Rip

, Nierman

M.C.

, Sierts

J.A.

et al. 2005. Gene therapy for lipoprotein lipase deficiency: working toward clinical application. Hum. Gene Ther., 16:1276–1286.

54.

Ross

C.J.D.

, Twisk

, Meulenberg

J.M.

et al. 2004. Long-term correction of murine lipoprotein lipase deficiency with AAV1-mediated gene transfer of the naturally occurring LPL(S447X) beneficial mutation. Hum. Gene Ther., 15:906–919.

55.

Ross

C.J.D.

, Liu

G.Q.

, Kuivenhoven

J.A.

et al. 2005. Complete rescue of lipoprotein lipase-deficient mice by somatic gene transfer of the naturally occurring LPLS447X beneficial mutation. Arterioscler. Thromb. Vasc. Biol., 25:2143–2150.

56.

Ross

C.J.D.

, Twisk

, Bakker

A.C.

et al. 2006. Correction of feline lipoprotein lipase deficiency with adeno-associated virus serotype 1-mediated gene transfer of the lipoprotein lipase S447X beneficial mutation. Hum. Gene Ther., 17:487–499.

57.

Stocks

, Thorn

J.A.

, Galton

D.J.

1992. Lipoprotein lipase genotypes for a common premature termination codon mutation detected by PCR-mediated site-directed mutagenesis and restriction digestion. J. Lipid Res., 33:853–857.

58.

Stroes

E.S.

, Nierman

M.C.

, Meulenberg

J.J.

et al. 2008. Intramuscular administration of AAV1-lipoprotein lipase S447X lowers triglycerides in lipoprotein lipase-deficient patients. Arterioscler. Thromb. Vasc. Biol., 28:2303–2304.

59.

Wion

K.L.

, Kirchgessner

T.G.

, Lusis

A.J.

et al. 1987. Human lipoprotein lipase complementary DNA sequence. Science, 235:1638–1641.

60.

Wittekoek

M.E.

, Pimstone

S.N.

, Reymer

P.W.

et al. 1998. A common mutation in the lipoprotein lipase gene (N291S) alters the lipoprotein phenotype and risk for cardiovascular disease in patients with familial hypercholesterolemia. Circulation, 97:729–735.

61.

Wittrup

H.H.

, Tybjaerg-Hansen

, Nordestgaard

B.G.

1999. Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease. A meta-analysis. Circulation, 99:2901–2907.

62.

Wittrup

H.H.

, Nordestgaard

B.G.

, Steffensen

et al. 2002. Effect of gender on phenotypic expression of the S447X mutation in LPL: the Copenhagen City Heart Study. Atherosclerosis, 165:119–126.

63.

Wood

, Schertzer

, Hayden

, Ma

1993. Support for founder effect for two lipoprotein lipase (LPL) gene mutations in French Canadians by analysis of GT microsatellites flanking the LPL gene. Hum. Genet., 91:312–316.