Progeria medical therapy: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
Line 33: Line 33:
* 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)


===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==

Revision as of 17:33, 7 August 2019

Progeria Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Progeria from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Interventions

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Progeria medical therapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Progeria medical therapy

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Progeria medical therapy

CDC on Progeria medical therapy

Progeria medical therapy in the news

Blogs on Progeria medical therapy

Directions to Hospitals Treating Psoriasis

Risk calculators and risk factors for Progeria medical therapy

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

  • New investigational therapies for Hutchinson-Gilford progeria syndrome (HGPS) patients include the following:[1]

Lonafarnib

  • Lonafarnib is a farnesyltransferase inhibitor (FTI).[2]
  • 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 is administered orally twice a day.
  • Using lonafarnib on patients with HGPS shows good improvements on the following:[3][4]
    • Lonafarnib improves weight gain
    • Lonafarnib improves vascular distensibility
    • Lonafarnib improves vascular echodensity
    • Lonafarnib improves skeletal rigidity
    • Lonafarnib improves vascular stiffness
    • Lonafarnib improves bone rigidity
    • Lonafarnib improves neurosensory hearing
    • Lonafarnib reduces the prevalence of stroke and TIA
    • Lonafarnib improves headaches
    • Lonafarnib improves life span in patients with HGPS[5]

Everolimus

  • Everolimus is a rapamycin-like drug which is a mTOR inhibitor which improves cellular autophagy.[6][7][8]
  • 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)


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.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Progeria_medical_therapy&oldid=1578598"