Cystinosis: Research & Drug Discovery Data

Drug discovery

drugs

With orphan designations

Overview

Cystinosis is an autosomal recessive lysosomal storage disorder caused by CTNS gene mutations, leading to cystine crystal accumulation and multi-organ damage [1][6][12]. Primarily affecting the kidneys, it manifests as Fanconi syndrome in infancy, progressing to end-stage renal disease (ESRD) by adolescence without treatment [3][8][16]. Ocular involvement causes photophobia and corneal ulcers [1][16]. Therapies include cysteamine to reduce intracellular cystine and kidney transplantation, though systemic complications persist [3][8][13].

Population

Incidence: 1 in 100,000–200,000 live births [1][12][17]; ~500–600 U.S. cases [16]
Carrier rate: ~1:30–200 [9][14]; potential underdiagnosis suggested by genetic studies [9][14]

Burden

Renal: ESRD in 74% by adolescence [4]; transplant survival improves outcomes but systemic progression continues [18]
Multisystem: Myopathy (79%), hypothyroidism (72%), growth failure (56%), and mortality (25.6%) [4][16]
Lifelong impact: Daily cysteamine dosing, corneal transplants, and high treatment costs [3][4][16]

(Word count: 68 words for overview)

Therapies

Cystine-depleting agents: Oral cysteamine (Cystagon®, Procysbi®) and ocular formulations (Cystadrops®) [3][8][11]
Renal replacement: 74% develop ESRD requiring transplantation/dialysis [4][18]
Investigational: AVROBIO's AVR-RD-04 gene therapy (Phase I/II) [3][13]

Categories: rare bone diseases, rare developmental anomalies during embryogenesis, rare endocrine diseases, rare genetic diseases, rare inborn errors of metabolism, rare renal diseases

Research Papers

585 drug discovery papers related to Cystinosis, with 6 first-in-class and 2 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate.

2026-06-15 | Silent but Severe: Transplant Renal Artery Stenosis Causing Acute Graft Dysfunction in a Child With Cystinosis.

Transplant renal artery stenosis (TRAS) is a potentially reversible vascular complication after kidney transplantation and an important cause of graft dysfunction in children. It usually presents with hypertension and/or impaired graft function but may occasionally remain clinically silent. We report an 11-year-old girl with cystinosis who underwent living-donor kidney transplantation outside our national, regulated transplant program and was referred to our center for follow-up. Early post-transplant Doppler ultrasonography was normal. At 10 weeks post-transplant, she developed an asymptomatic but severe rise in serum creatinine without hypertension. Imaging revealed a short, focal stenosis at the arterial anastomosis. Percutaneous transluminal angioplasty was successfully performed, followed by short-term anticoagulation and antiplatelet therapy, with rapid and sustained recovery of graft function. This case highlights that TRAS may present without hypertension and underscores the importance of careful surveillance, particularly in children transplanted outside regulated transplant programs.

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2026-05-20 | Which genetic syndromes have a gene or molecular therapy?

Gene and molecular therapies are being actively developed and show promise for genetic syndromes such as cystinosis, Pompe's disease, GM1 gangliosidosis, and hemophilia B, though further research is necessary to confirm their broader efficacy and safety profiles.

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2026-04-30 | A hydrophilic interaction liquid chromatography-tandem mass spectrometry method for the quantification of intracellular cystine and its application in cystinosis research.

Cystinosis is a rare, lysosomal storage disorder caused by mutations in the CTNS gene encoding the lysosomal cystine transporter, resulting in lysosomal cystine accumulation, the phenotypic hallmark of cystinosis, and progressive cellular dysfunction. Accurate quantification of cystine levels is therefore essential for assessing lysosomal transport deficiency and treatment response. In vitro cell models provide a controlled platform to investigate disease mechanisms and to evaluate emerging therapeutic strategies. To determine intracellular cystine concentrations in these models, adequate sample preparation, storage, and highly sensitive analytical methods are essential. In this work, a rapid hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method was developed for the direct determination of cystine in cellular extracts. Use of a PEEK-lined HILIC-Z column proved essential to minimize metal-induced peak tailing and improve chromatographic performance. The total run time of 5 min enabled high-throughput analysis, facilitating efficient screening of novel therapeutic approaches in cellular systems. Validation demonstrated excellent linearity (R2 ≥ 0.9986) and a lower limit of quantification (LLOQ) of 12.5 nM, representing a > 8-fold improvement over reported reversed-phase LC methods. Addition of N-ethylmaleimide (NEM) prior to cell lysis effectively limited cysteine oxidation and maintained sample stability at 4 °C. Applicability was demonstrated in an isogenic laboratory HEK293T cell model, where CTNS-knockout (KO) cells exhibited significantly elevated intracellular cystine levels compared to wild-type (WT) cells. As additional controls, elevated levels were successfully restored following cysteamine treatment or lentiviral-vector (LV)-mediated CTNS protein re-expression. The developed method hence provides a sensitive and reliable analytical platform for in vitro evaluation of novel therapeutic strategies in cystinosis research.

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2026-06-15 | Silent but Severe: Transplant Renal Artery Stenosis Causing Acute Graft Dysfunction in a Child With Cystinosis.

Open article ↗

2026-05-20 | Which genetic syndromes have a gene or molecular therapy?

Open article ↗

2026-04-30 | A hydrophilic interaction liquid chromatography-tandem mass spectrometry method for the quantification of intracellular cystine and its application in cystinosis research.

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Drug Discovery Landscape

12 orphan drug designations for Cystinosis, including 4 approved therapies.

Drug	Therapy type	Regulator	Orphan designation	Approval	Sponsor
N-acetylcysteine amide	small molecules	FDA	2021-09-07	—	Nacuity Pharmaceuticals, Inc.
Autologous CD34+ cells transduced with a lentiviral RNA vector that results in integrated cDNA encoding for functional cystinosin	cell therapies	EMA	2021-02-19	—	Novartis Europharm Limited
autologous CD34+ enriched cells transduced with a lentiviral vector containing RNA resulting in codon-optimized cDNA encoding for functional human cystinosin	cell therapies	FDA	2020-03-04	—	Novartis Pharmaceuticals Corporation
6'-(R)-methyl-5-O-(5-amino-5,6-dideoxy-alpha-L-talofuranosyl)-paromamine sulfate	small molecules	FDA	2018-04-26	—	ELOXX Pharmaceuticals, Inc.
Cysteamine hydrochloride	small molecules	EMA	2014-10-15	—	Lucane Pharma SA
Mercaptamine bitartrate [Procysbi]	small molecules	EMA	2010-09-20	—	Chiesi Farmaceutici S.p.A.
Cysteamine hydrochloride [Cystadrops]	small molecules	EMA	2008-11-07	2017-01-23	Recordati Rare Diseases
cysteamine enteric coated [PROCYSBI]	small molecules	FDA	2006-10-24	2013-04-30	Horizon Therapeutics USA, Inc.
Cysteamine hydrochloride [Cystaran]	small molecules	FDA	1997-08-19	2012-10-02	Leadiant Biosciences, Inc.
Cysteamine [Cystagon]	small molecules	FDA	1991-01-25	1994-08-15	Mylan Laboratories, Inc.
Phosphocysteamine	small molecules	FDA	1988-09-12	—	Medea Research Laboratories
Cysteamine	small molecules	FDA	1986-05-01	—	Thoene, Jess G., M.D.

Cystinosis

Cystinosis

Cystinosis

Overview

Population

Burden

Therapies

Categories: rare bone diseases, rare developmental anomalies during embryogenesis, rare endocrine diseases, rare genetic diseases, rare inborn errors of metabolism, rare renal diseases

Research Papers

2026-06-15 | Silent but Severe: Transplant Renal Artery Stenosis Causing Acute Graft Dysfunction in a Child With Cystinosis.

2026-05-20 | Which genetic syndromes have a gene or molecular therapy?

2026-04-30 | A hydrophilic interaction liquid chromatography-tandem mass spectrometry method for the quantification of intracellular cystine and its application in cystinosis research.

2026-06-15 | Silent but Severe: Transplant Renal Artery Stenosis Causing Acute Graft Dysfunction in a Child With Cystinosis.

2026-05-20 | Which genetic syndromes have a gene or molecular therapy?

2026-04-30 | A hydrophilic interaction liquid chromatography-tandem mass spectrometry method for the quantification of intracellular cystine and its application in cystinosis research.

Drug Discovery Landscape

Updated: Jul 28, 2026