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==Overview==
==Overview==
There is no treatment for Hutchinson-Gilford progeria syndrome (HGPS); the mainstay of therapy is supportive care. But the good news is that there are new investigational therapies for Hutchinson-Gilford progeria syndrome (HGPS) patients which include lonafarnib and everolimus.
There is no treatment for [[Hutchinson-Gilford progeria syndrome]] ([[HGPS]]); the mainstay of therapy is supportive care. But the good news is that there are new investigational therapies for [[Hutchinson-Gilford progeria syndrome]] ([[HGPS]]) patients which include [[lonafarnib]] and [[everolimus]].


==Medical Therapy==
==Medical Therapy==
*New investigational therapies for Hutchinson-Gilford progeria syndrome (HGPS) patients include the following:<ref name="pmid20301300">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al.| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301300 | doi= | pmc= | url= }}</ref>
*New investigational therapies for [[Hutchinson-Gilford progeria syndrome]] ([[HGPS]]) patients include the following:<ref name="pmid20301300">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al.| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301300 | doi= | pmc= | url= }}</ref>
**Farnesyltransferase inhibitor (FTI)- [[Lonafarnib]]
**[[Farnesyltransferase]] inhibitor (FTI)- [[Lonafarnib]]
**mTOR inhibitor- [[Everolimus]]
**[[mTOR]] inhibitor- [[Everolimus]]


'''Lonafarnib'''
'''Lonafarnib'''


* Lonafarnib is a farnesyltransferase inhibitor (FTI).<ref name="pmid203013002">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al.| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301300 | doi= | pmc= | url= }}</ref>
*[[Lonafarnib]] is a farnesyltransferase inhibitor (FTI).<ref name="pmid203013002">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al.| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301300 | doi= | pmc= | url= }}</ref>
* Mechanism action of lonafarnib is it may inhibit the formation of the truncated lamin A protein which is called progerin.
* Mechanism action of [[lonafarnib]] is it may inhibit the formation of the truncated [[lamin A]] protein which is called [[progerin]].
* Lonafarnib also inhibit anchoring of the protein lamin A to the inner surface of the nuclear membrane, thus significantly improving disease results in Hutchinson-Gilford progeria syndrome (HGPS) patients.
*[[Lonafarnib]] also inhibit anchoring of the protein [[lamin A]] to the inner surface of the nuclear membrane, thus significantly improving disease results in [[Hutchinson-Gilford progeria syndrome]] ([[HGPS]]) patients.
*Lonafarnib is administered orally twice a day.
*[[Lonafarnib]]<nowiki/>is administered orally twice a day.
*Using lonafarnib on patients with HGPS shows good improvements on the following:<ref name="pmid23012407">{{cite journal| author=Gordon LB, Kleinman ME, Miller DT, Neuberg DS, Giobbie-Hurder A, Gerhard-Herman M et al.| title=Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome. | journal=Proc Natl Acad Sci U S A | year= 2012 | volume= 109 | issue= 41 | pages= 16666-71 | pmid=23012407 | doi=10.1073/pnas.1202529109 | pmc=3478615 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23012407  }}</ref><ref name="pmid23897869">{{cite journal| author=Ullrich NJ, Kieran MW, Miller DT, Gordon LB, Cho YJ, Silvera VM et al.| title=Neurologic features of Hutchinson-Gilford progeria syndrome after lonafarnib treatment. | journal=Neurology | year= 2013 | volume= 81 | issue= 5 | pages= 427-30 | pmid=23897869 | doi=10.1212/WNL.0b013e31829d85c0 | pmc=3776537 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23897869  }}</ref>
*Using lonafarnib on patients with [[Hutchinson-Gilford progeria syndrome]] ([[HGPS]]) shows good improvements on the following:<ref name="pmid23012407">{{cite journal| author=Gordon LB, Kleinman ME, Miller DT, Neuberg DS, Giobbie-Hurder A, Gerhard-Herman M et al.| title=Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome. | journal=Proc Natl Acad Sci U S A | year= 2012 | volume= 109 | issue= 41 | pages= 16666-71 | pmid=23012407 | doi=10.1073/pnas.1202529109 | pmc=3478615 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23012407  }}</ref><ref name="pmid23897869">{{cite journal| author=Ullrich NJ, Kieran MW, Miller DT, Gordon LB, Cho YJ, Silvera VM et al.| title=Neurologic features of Hutchinson-Gilford progeria syndrome after lonafarnib treatment. | journal=Neurology | year= 2013 | volume= 81 | issue= 5 | pages= 427-30 | pmid=23897869 | doi=10.1212/WNL.0b013e31829d85c0 | pmc=3776537 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23897869  }}</ref>
**Lonafarnib improves weight gain
**[[Lonafarnib]] improves weight gain
**Lonafarnib improves vascular distensibility
**[[Lonafarnib]] improves [[vascular]] distensibility
**Lonafarnib improves vascular echodensity
**[[Lonafarnib]] improves [[vascular]] echodensity
**Lonafarnib improves skeletal rigidity
**[[Lonafarnib]] improves [[Skeletal|skeleta]]<nowiki/>l rigidity
**Lonafarnib improves vascular stiffness
**[[Lonafarnib]] improves vascular stiffness
**Lonafarnib improves bone rigidity
**[[Lonafarnib]] improves [[bone]] rigidity
**Lonafarnib improves neurosensory hearing
**[[Lonafarnib]] improves neurosensory hearing
**Lonafarnib reduces the prevalence of stroke and TIA
**[[Lonafarnib]] reduces the prevalence of [[stroke]] and [[Transient ischemic attack|TIA]]
**Lonafarnib improves headaches
**[[Lonafarnib]] improves [[Headache|headaches]]
**Lonafarnib improves life span in patients with HGPS<ref name="pmid24795390">{{cite journal| author=Gordon LB, Massaro J, D'Agostino RB, Campbell SE, Brazier J, Brown WT et al.| title=Impact of farnesylation inhibitors on survival in Hutchinson-Gilford progeria syndrome. | journal=Circulation | year= 2014 | volume= 130 | issue= 1 | pages= 27-34 | pmid=24795390 | doi=10.1161/CIRCULATIONAHA.113.008285 | pmc=4082404 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24795390  }}</ref>
**[[Lonafarnib]] improves life span in patients with HGPS<ref name="pmid24795390">{{cite journal| author=Gordon LB, Massaro J, D'Agostino RB, Campbell SE, Brazier J, Brown WT et al.| title=Impact of farnesylation inhibitors on survival in Hutchinson-Gilford progeria syndrome. | journal=Circulation | year= 2014 | volume= 130 | issue= 1 | pages= 27-34 | pmid=24795390 | doi=10.1161/CIRCULATIONAHA.113.008285 | pmc=4082404 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24795390  }}</ref>


'''Everolimus'''
'''Everolimus'''


* Everolimus is a rapamycin-like drug which is a mTOR inhibitor which improves cellular autophagy.<ref name="pmid22297442">{{cite journal| author=Cenni V, Capanni C, Columbaro M, Ortolani M, D'Apice MR, Novelli G et al.| title=Autophagic degradation of farnesylated prelamin A as a therapeutic approach to lamin-linked progeria. | journal=Eur J Histochem | year= 2011 | volume= 55 | issue= 4 | pages= e36 | pmid=22297442 | doi=10.4081/ejh.2011.e36 | pmc=3284238 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22297442  }}</ref><ref name="pmid21670498">{{cite journal| author=Cao K, Blair CD, Faddah DA, Kieckhaefer JE, Olive M, Erdos MR et al.| title=Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts. | journal=J Clin Invest | year= 2011 | volume= 121 | issue= 7 | pages= 2833-44 | pmid=21670498 | doi=10.1172/JCI43578 | pmc=3223819 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21670498  }}</ref><ref name="pmid203013003">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al.| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301300 | doi= | pmc= | url= }}</ref>
*[[Everolimus]] is a [[rapamycin]]-like drug which is a [[mTOR]] inhibitor which improves cellular [[autophagy]].<ref name="pmid22297442">{{cite journal| author=Cenni V, Capanni C, Columbaro M, Ortolani M, D'Apice MR, Novelli G et al.| title=Autophagic degradation of farnesylated prelamin A as a therapeutic approach to lamin-linked progeria. | journal=Eur J Histochem | year= 2011 | volume= 55 | issue= 4 | pages= e36 | pmid=22297442 | doi=10.4081/ejh.2011.e36 | pmc=3284238 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22297442  }}</ref><ref name="pmid21670498">{{cite journal| author=Cao K, Blair CD, Faddah DA, Kieckhaefer JE, Olive M, Erdos MR et al.| title=Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts. | journal=J Clin Invest | year= 2011 | volume= 121 | issue= 7 | pages= 2833-44 | pmid=21670498 | doi=10.1172/JCI43578 | pmc=3223819 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21670498  }}</ref><ref name="pmid203013003">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al.| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301300 | doi= | pmc= | url= }}</ref>
* Everolimus is a oral medication and should be given once daily on daily basis.
*[[Everolimus]] is a oral medication and should be given once daily on daily basis.
*Everolimus mechanism of action is it improves cellular phenotypes in HGPS fibroblasts via increased autophagy(self-eating)
*[[Everolimus]] mechanism of action is it improves cellular phenotypes in HGPS fibroblasts via increased [[autophagy]](self-eating)




Latest revision as of 02:02, 14 August 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]

Overview

There is no treatment for Hutchinson-Gilford progeria syndrome (HGPS); the mainstay of therapy is supportive care. But the good news is that there are new investigational therapies for Hutchinson-Gilford progeria syndrome (HGPS) patients which include lonafarnib and everolimus.

Medical Therapy

Lonafarnib

Everolimus


References

  1. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301300.
  2. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301300.
  3. ↑ Gordon LB, Kleinman ME, Miller DT, Neuberg DS, Giobbie-Hurder A, Gerhard-Herman M; et al. (2012). "Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome". Proc Natl Acad Sci U S A. 109 (41): 16666–71. doi:10.1073/pnas.1202529109. PMC 3478615. PMID 23012407.
  4. ↑ Ullrich NJ, Kieran MW, Miller DT, Gordon LB, Cho YJ, Silvera VM; et al. (2013). "Neurologic features of Hutchinson-Gilford progeria syndrome after lonafarnib treatment". Neurology. 81 (5): 427–30. doi:10.1212/WNL.0b013e31829d85c0. PMC 3776537. PMID 23897869.
  5. ↑ Gordon LB, Massaro J, D'Agostino RB, Campbell SE, Brazier J, Brown WT; et al. (2014). "Impact of farnesylation inhibitors on survival in Hutchinson-Gilford progeria syndrome". Circulation. 130 (1): 27–34. doi:10.1161/CIRCULATIONAHA.113.008285. PMC 4082404. PMID 24795390.
  6. ↑ Cenni V, Capanni C, Columbaro M, Ortolani M, D'Apice MR, Novelli G; et al. (2011). "Autophagic degradation of farnesylated prelamin A as a therapeutic approach to lamin-linked progeria". Eur J Histochem. 55 (4): e36. doi:10.4081/ejh.2011.e36. PMC 3284238. PMID 22297442.
  7. ↑ Cao K, Blair CD, Faddah DA, Kieckhaefer JE, Olive M, Erdos MR; et al. (2011). "Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts". J Clin Invest. 121 (7): 2833–44. doi:10.1172/JCI43578. PMC 3223819. PMID 21670498.
  8. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301300.

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