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Transthyretin-related familial amyloidotic polyneuropathy-Progress in Kumamoto, Japan (1967-2010)-.

Araki S, Ando Y - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Bottom Line: As of today, reports of about 100 different points of single or two mutations, or a deletion in the transthyretin (TTR) gene, have been published.The authors' group has made pioneer works for study of FAP in the world.The focus on therapy in amylodosis will increase sharply as an impetus in near future, and successful treatments are expected.

View Article: PubMed Central - PubMed

Affiliation: Kumamoto University, Japan. somu@omutatenryo-hp.jp

ABSTRACT
The authors reviewed contribution of Kumamoto University group to the progress of the studies on transthyretin (TTR)-related familial amyloidotic polyneuropathy (TTR-related FAP) for 42 years (from 1967 to 2009). Andrade (1952) first described a large group of patients with FAP in Portugal and Araki et al. (1967) in second discovered similar FAP patients in Arao, Kumamoto, Japan. Owing to progress in biochemical and molecular genetic analyses, FAP is now believed to occur worldwide. As of today, reports of about 100 different points of single or two mutations, or a deletion in the transthyretin (TTR) gene, have been published. The authors' group has made pioneer works for study of FAP in the world. The focus on therapy in amylodosis will increase sharply as an impetus in near future, and successful treatments are expected.

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Related in: MedlinePlus

Working hypothesis for TTR amyloid formation and therapies. On the basis of amyloid formation mechanism, several promising therapies are considering.
© Copyright Policy - open-access
Related In: Results  -  Collection


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fig05: Working hypothesis for TTR amyloid formation and therapies. On the basis of amyloid formation mechanism, several promising therapies are considering.

Mentions: Although liver transplantation is the only therapy to halt the clinical manifestations of transthyretin (TTR) related FAP, the therapy has given rise to have several problems. An alternative treatment is needed. After the precursor protein of amyloid fibrils in FAP was determined in 1983, several different therapeutic approaches have been investigated as an essential therapy for FAP: (1) reduction of variant TTR levels in plasma, (2) down-regulation of TTR gene of mRNA (3) inhibition of amyloid deposition, (4) stabilization of the tetrameric TTR structure and (5) replacement of the variant TTR gene with the normal TTR gene (which can be achieved by liver transplantation or by gene therapy) (Fig. 5). In our research group, as gene therapy for variant TTR gene, gene conversion therapy using wild type TTR single stranded oligonucleotides, or gene silencing using siRNA for variant TTR gene has been studied. In addition, effect of antibody therapy for targeting misfiled variant TTR has been examined in vivo. Both projects are now on going, and getting better results in vivo. In near future, these therapeutic projects may be in phase study.


Transthyretin-related familial amyloidotic polyneuropathy-Progress in Kumamoto, Japan (1967-2010)-.

Araki S, Ando Y - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Working hypothesis for TTR amyloid formation and therapies. On the basis of amyloid formation mechanism, several promising therapies are considering.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3066541&req=5

fig05: Working hypothesis for TTR amyloid formation and therapies. On the basis of amyloid formation mechanism, several promising therapies are considering.
Mentions: Although liver transplantation is the only therapy to halt the clinical manifestations of transthyretin (TTR) related FAP, the therapy has given rise to have several problems. An alternative treatment is needed. After the precursor protein of amyloid fibrils in FAP was determined in 1983, several different therapeutic approaches have been investigated as an essential therapy for FAP: (1) reduction of variant TTR levels in plasma, (2) down-regulation of TTR gene of mRNA (3) inhibition of amyloid deposition, (4) stabilization of the tetrameric TTR structure and (5) replacement of the variant TTR gene with the normal TTR gene (which can be achieved by liver transplantation or by gene therapy) (Fig. 5). In our research group, as gene therapy for variant TTR gene, gene conversion therapy using wild type TTR single stranded oligonucleotides, or gene silencing using siRNA for variant TTR gene has been studied. In addition, effect of antibody therapy for targeting misfiled variant TTR has been examined in vivo. Both projects are now on going, and getting better results in vivo. In near future, these therapeutic projects may be in phase study.

Bottom Line: As of today, reports of about 100 different points of single or two mutations, or a deletion in the transthyretin (TTR) gene, have been published.The authors' group has made pioneer works for study of FAP in the world.The focus on therapy in amylodosis will increase sharply as an impetus in near future, and successful treatments are expected.

View Article: PubMed Central - PubMed

Affiliation: Kumamoto University, Japan. somu@omutatenryo-hp.jp

ABSTRACT
The authors reviewed contribution of Kumamoto University group to the progress of the studies on transthyretin (TTR)-related familial amyloidotic polyneuropathy (TTR-related FAP) for 42 years (from 1967 to 2009). Andrade (1952) first described a large group of patients with FAP in Portugal and Araki et al. (1967) in second discovered similar FAP patients in Arao, Kumamoto, Japan. Owing to progress in biochemical and molecular genetic analyses, FAP is now believed to occur worldwide. As of today, reports of about 100 different points of single or two mutations, or a deletion in the transthyretin (TTR) gene, have been published. The authors' group has made pioneer works for study of FAP in the world. The focus on therapy in amylodosis will increase sharply as an impetus in near future, and successful treatments are expected.

Show MeSH
Related in: MedlinePlus