TABLE 3.

Treatment strategies verified only in vitro for tackling HGPS

Type of agents	Strategy	Effects	Ref.
Small‐molecule compound	Treatment with inhibitors to prevent progerin farnesylation and geranylgeranylation	Treatment of progeria cells with the farnesyltransferase inhibitor FTI‐277 and the geranylgeranyltransferase inhibitor GGTI‐2147 successfully corrected the disease‐associated changes in chromosome territory positions and chromosome dynamics	Mehta et al. (2011)
	Treatment with rapamycin alone	Rapamycin treatment of progeria cells lowered the levels of progerin and wild‐type prelamin A. It could also increase the relative expression of ZMPSTE24, which is a prelamin A endoprotease	Cenni et al. (2011)
		Rapamycin treatment of progeria cells abolished nuclear blebbing, delayed the onset of cellular senescence, and enhanced progerin degradation	Cao et al. (2011)
		Treatment of muscle‐derived stem/progenitor cells obtained from progeroid mice with rapamycin improved the capacity of myogenic and chondrogenic differentiation, and reduced the extent of apoptosis and senescence	Kawakami et al. (2019)
	Treatment with a farnesyltransferase inhibitor alone	Treatment of GFP‐progerin marrow‐isolated adult multilineage inducible MIAMI cells with FTI‐277 reduced the number of abnormal nuclei, decreased the stiffness in both cytoplasmic and nuclear regions, and enhanced the self‐renewal capacity of those cells	Pacheco et al. (2014)
	Treatment with rapamycin and all‐trans retinoic acid	Treatment of progeria cells with rapamycin, along with all‐trans retinoic acid, reduced the levels of progerin and prelamin A, and increased the lamin A to progerin ratio.	Pellegrini et al. (2015)
	Treatment with rapamycin and DMSO	Treatment of progeria cells with DMSO and rapamycin ameliorated nuclear shape abnormalities	Akinci et al. (2017)
	Treatment with rapamycin and a farnesyltransferase inhibitor	Treatment of progeria cells with the farnesyltransferase inhibitor (viz., FTI‐277) and rapamycin restored the genome organization in progeria cells and improved the ability of the cells to repair damaged DNA	Bikkul et al. (2018)
	Treatment with N6‐isopentenyladenosine	Treatment of progeria cells with N6‐isopentenyladenosine ameliorated nuclear shape abnormalities and led to a redistribution of prelamin A away from the inner nuclear envelope	Bifulco et al. (2013)
	Treatment with sulforaphane	Treatment of progeria cells with sulforaphane enhanced progerin clearance, and reduced the extent of DNA damage associated with HGPS	Gabriel et al. (2015)
	Treatment with methylene blue	Treatment of progeria cells with methylene blue alleviated mitochondrial defects caused by HGPS, rescued nuclear shape abnormalities and perinuclear heterochromatin loss, and corrected misregulated gene expression	Xiong et al. (2016)
	Treatment with 1α,25‐dihydroxyvitamin D3	Treatment of progeria cells with 1α,25‐dihydroxyvitamin D3 reduced progerin production, and alleviated some of the disease phenotypes, including nuclear morphological abnormalities, DNA repair defects, and premature senescence	Kreienkamp et al. (2016)
	Treatment with temsirolimus	Treatment of progeria cells with temsirolimus decreased the progerin level, enhanced cell proliferation, and reduced the number of misshapen nuclei	Gabriel et al. (2016)
	Treatment with metformin	Treatment of MSCs derived from progeria fibroblasts with metformin led to a reduction in progerin expression, and ameliorated nuclear shape abnormalities	Egesipe et al. (2016)
		Treatment of progeria cells with metformin delayed cell senescence caused by HGPS, reduced ROS production, and decreased the number of DNA damage foci	Park and Shin (2017)
	Treatment with the ROCK inhibitor	Treatment of progeria cells with the ROCK inhibitor Y‐27632 decreased the number of misshapen nuclei and the frequency of DNA double‐strand breaks	Kang et al. (2017)
	Treatment with a farnesyltransferase inhibitor and sulforaphane	Treatment of progeria cells with lonafarnib and sulforaphane enhanced progerin clearance, prevented prelamin A accumulation, ameliorated nuclear shape abnormalities, and reduced the number of DNA damage foci	Gabriel et al. (2017)
	Treatment with baricitinib	Treatment of progeria cells with baricitinib restored cellular homeostasis, delayed cell senescence, and reduced the expression of proinflammatory markers	Liu et al. (2019)
	Treatment with leptomycin B	Treatment of progeria cells with leptomycin B reduced the number of senescent cells, ameliorated nuclear shape abnormalities, and rescued the loss of heterochromatin	Garcia‐Aguirre et al. (2019)
	Treatment with N‐acetyl cysteine (NAC)	Treatment of progeria cells with NAC rescued the ability to repair double‐strand breaks, and decreased the population‐doubling time	Richards et al. (2011)
	Treatment with vitamin C and/or quercetin	Treatment of HGPS hMSCs with vitamin C and/or quercetin inhibited progerin production, decreased the population‐doubling time, decreased senescence‐associated β‐galactosidase positivity, and increased the proliferative ability of the cells	Geng et al. (2019)
	Treatment with S‐adenosyl methionine (SAMe)	Treatment of progeria cells with SAMe increased the proliferative capacity of the cells, and decreased senescence‐associated β‐galactosidase positivity	Mateos et al. (2018)
	Treatment with CP‐466722	Treatment of progeria cells with CP‐466722 induced mitochondrial functional recovery, reduced progerin accumulation, and ameliorated nuclear defects	Kuk et al. (2019)
Therapeutic nucleic acid	Lentiviral infection for overexpression of SIRT6	Overexpression of SIRT6 in progeria cells led to a reduction in the frequency of SA‐β‐gal positivity, and reduced the number of misshapen nuclei	Endisha et al. (2015)
	Transduction with an adenoviral vector for the correction of the LMNA mutation	Transduction of iPSCs derived from HGPS fibroblasts with the viral vector restored the expression of wild‐type lamin A. abolished progerin expression, decelerated senescence, and ameliorated nuclear shape abnormalities	Liu et al. (2011)
	Treatment with morpholino antisense oligonucleotides for progerin downregulation	Antisense‐based progerin downregulation reduced the accumulation of progerin and/or other truncated prelamin A isoforms, ameliorated nuclear shape abnormalities, and reduced senescence in HGPS‐like patients' cells	Harhouri et al. (2016)
	Transfection with human telomerase reverse transcriptase (hTERT) mRNA	Transfection of short telomere‐containing progeria cells with hTERT mRNA increased the proliferative capacity and lifespan of the cells, reduced the level of senescence, and ameliorated nuclear shape abnormalities	Li et al. (2019)