Progeria medical therapy: Difference between revisions

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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.
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]].


OR
==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>
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
**[[Farnesyltransferase]] inhibitor (FTI)- [[Lonafarnib]]
 
**[[mTOR]] inhibitor- [[Everolimus]]
OR
 
The majority of cases of [disease name] are self-limited and require only supportive care.
 
OR
 
[Disease name] is a medical emergency and requires prompt treatment.
 
OR
 
The mainstay of treatment for [disease name] is [therapy].
 
OR
 
The optimal therapy for [malignancy name] depends on the stage at diagnosis.
 
OR
 
[Therapy] is recommended among all patients who develop [disease name].
 
OR
 
Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
 
OR
 
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].


OR
'''Lonafarnib'''


Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
*[[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]].
*[[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]]<nowiki/>is administered orally twice a day.
*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 [[vascular]] distensibility
**[[Lonafarnib]] improves [[vascular]] echodensity
**[[Lonafarnib]] improves [[Skeletal|skeleta]]<nowiki/>l rigidity
**[[Lonafarnib]] improves vascular stiffness
**[[Lonafarnib]] improves [[bone]] rigidity
**[[Lonafarnib]] improves neurosensory hearing
**[[Lonafarnib]] reduces the prevalence of [[stroke]] and [[Transient ischemic attack|TIA]]
**[[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>


OR
'''Everolimus'''


Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
*[[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]] mechanism of action is it improves cellular phenotypes in HGPS fibroblasts via increased [[autophagy]](self-eating)


==Medical Therapy==
*Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
*Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
*Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
*Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
===Disease Name===


* '''1 Stage 1 - Name of stage'''
** 1.1 '''Specific Organ system involved 1'''
*** 1.1.1 '''Adult'''
**** Preferred regimen (1): [[drug name]] 100 mg PO q12h for 10-21 days '''(Contraindications/specific instructions)''' 
**** Preferred regimen (2): [[drug name]] 500 mg PO q8h for 14-21 days
**** Preferred regimen (3): [[drug name]] 500 mg q12h for 14-21 days
**** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
**** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
**** Alternative regimen (3): [[drug name]] 500 mg PO q6h for 14–21 days
*** 1.1.2 '''Pediatric'''
**** 1.1.2.1 (Specific population e.g. '''children < 8 years of age''')
***** Preferred regimen (1): [[drug name]] 50 mg/kg PO per day q8h (maximum, 500 mg per dose) 
***** Preferred regimen (2): [[drug name]] 30 mg/kg PO per day in 2 divided doses (maximum, 500 mg per dose)
***** Alternative regimen (1): [[drug name]]10 mg/kg PO q6h (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
****1.1.2.2 (Specific population e.g. '<nowiki/>'''''children < 8 years of age'''''')
***** Preferred regimen (1): [[drug name]] 4 mg/kg/day PO q12h（maximum, 100 mg per dose）
***** Alternative regimen (1): [[drug name]] 10 mg/kg PO q6h (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h (maximum, 500 mg per dose) 
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
** 1.2 '''Specific Organ system involved 2'''
*** 1.2.1 '''Adult'''
**** Preferred regimen (1): [[drug name]] 500 mg PO q8h
*** 1.2.2  '''Pediatric'''
**** Preferred regimen (1): [[drug name]] 50 mg/kg/day PO q8h (maximum, 500 mg per dose)


* 2 '''Stage 2 - Name of stage'''
*
** 2.1 '''Specific Organ system involved 1 '''
**: '''Note (1):'''
**: '''Note (2)''':
**: '''Note (3):'''
*** 2.1.1 '''Adult'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 2 g IV q24h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 2 g IV q8h for 14 (14–21) days
***** Alternative regimen (2): [[drug name]] 18–24 MU/day IV q4h for 14 (14–21) days
**** Oral regimen
***** Preferred regimen (1): [[drug name]] 500 mg PO q8h for 14 (14–21) days
***** Preferred regimen (2): [[drug name]] 100 mg PO q12h for 14 (14–21) days
***** Preferred regimen (3): [[drug name]] 500 mg PO q12h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
***** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
***** Alternative regimen (3):[[drug name]] 500 mg PO q6h for 14–21 days
*** 2.1.2 '''Pediatric'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
***** Alternative regimen (1): [[drug name]] 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
***** Alternative regimen (2):  [[drug name]] 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day) '<nowiki/>'''''(Contraindications/specific instructions)''''''
**** Oral regimen
***** Preferred regimen (1):  [[drug name]] 50 mg/kg/day PO q8h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Preferred regimen (2): [[drug name]] '''(for children aged ≥ 8 years)''' 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
***** Preferred regimen (3): [[drug name]] 30 mg/kg/day PO q12h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Alternative regimen (1):  [[drug name]] 10 mg/kg PO q6h 7–10 days  (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h for 14–21 days  (maximum, 500 mg per dose)
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h for 14–21 days  (maximum,500 mg per dose)
** 2.2  '<nowiki/>'''''Other Organ system involved 2''''''
**: '''Note (1):'''
**: '''Note (2)''':
**: '''Note (3):'''
*** 2.2.1 '''Adult'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 2 g IV q24h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 2 g IV q8h for 14 (14–21) days
***** Alternative regimen (2): [[drug name]] 18–24 MU/day IV q4h for 14 (14–21) days
**** Oral regimen
***** Preferred regimen (1): [[drug name]] 500 mg PO q8h for 14 (14–21) days
***** Preferred regimen (2): [[drug name]] 100 mg PO q12h for 14 (14–21) days
***** Preferred regimen (3): [[drug name]] 500 mg PO q12h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
***** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
***** Alternative regimen (3):[[drug name]] 500 mg PO q6h for 14–21 days
*** 2.2.2 '''Pediatric'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
***** Alternative regimen (1): [[drug name]] 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
***** Alternative regimen (2):  [[drug name]] 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day)
**** Oral regimen
***** Preferred regimen (1):  [[drug name]] 50 mg/kg/day PO q8h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Preferred regimen (2): [[drug name]] 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
***** Preferred regimen (3): [[drug name]] 30 mg/kg/day PO q12h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Alternative regimen (1):  [[drug name]] 10 mg/kg PO q6h 7–10 days  (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h for 14–21 days  (maximum, 500 mg per dose)
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h for 14–21 days  (maximum,500 mg per dose)


==References==
==References==

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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