Details of Disease

General Information of Disease (ID: DISH30B8)

Disease Name	Lateral sclerosis
Synonyms	PLS; adult-onset PLS; adult-onset primary lateral sclerosis; primary lateral sclerosis
Disease Class	8B61: Muscular atrophy
Definition	Primary lateral sclerosis (PLS) is an idiopathic non-familial motor neuron disease characterized by slowly progressive upper motor neuron dysfunction leading to spasticity, mild weakness in voluntary muscle movement, hyperreflexia, and loss of motor speech production.
Disease Hierarchy	DIS6XNI0: Hereditary motor neuron disease DISH30B8: Lateral sclerosis
ICD Code	ICD-11 ICD-11: 8B61
Disease Identifiers	MONDO ID MONDO_0018155 MESH ID D016472 UMLS CUI C0154682 MedGen ID 57591 Orphanet ID 35689 SNOMED CT ID 81211007

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 8 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Xaliproden	DM1JCW8	Phase 3	Small molecular drug	[1]
GDNF-producing adult stem cell therapy	DMTN0HI	Phase 2	NA	[2]
NSI-566	DMHHXC9	Phase 2	NA	[3]
Omigapil	DMH9RTV	Phase 2	Small molecular drug	[4]
Ozanezumab	DMRFS9M	Phase 2	Monoclonal antibody	[5]
Liatermin	DMENF5K	Phase 1/2	NA	[6]
SNN-0029	DMNV8SY	Phase 1/2	NA	[7]
Autologous bone marrow-derived mesenchymal stem cells	DMXURYQ	Phase 1	NA	[8]
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⏷ Show the Full List of 8 Drug(s)

This Disease is Treated as An Indication in 1 Discontinued Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
TRO-40303	DMZ98Y4	Discontinued in Phase 2	Small molecular drug	[9]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
C9orf72	TTA4SHR	Limited	Genetic Variation	[10]
PNPLA6	TTWAQU2	Limited	Biomarker	[11]
SOD1	TTP9K3Q	Definitive	Biomarker	[12]
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This Disease Is Related to 6 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
SPAST	OTIF3AJI	Limited	Genetic Variation	[13]
SPG7	OT8OY9ST	Supportive	Autosomal dominant	[14]
ALS2	OT8BAM04	Strong	Genetic Variation	[15]
FIG4	OT501PY9	Strong	Genetic Variation	[16]
IGFALS	OTTWCZYM	Strong	Biomarker	[12]
PRDX3	OTLB2WEU	Strong	Biomarker	[17]
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⏷ Show the Full List of 6 DOT(s)

References

1	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001601)
2	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
3	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025566)
4	ClinicalTrials.gov (NCT00649961) Melatonin As A Novel Neuroprotectant In Preterm Infants- Dosage Study. U.S. National Institutes of Health.
5	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8254).
6	ClinicalTrials.gov (NCT00111982) Trial of Extended Treatment With Liatermin (r-metHuGDNF) Administered by Continuous Intraputaminal (IPu)Infusion to Subjects With Idiopathic Parkinson's Disease Who Have Completed a Previous Trial of Liatermin. U.S. National Institutes of Health.
7	ClinicalTrials.gov (NCT01384162) An Open Label, Safety and Tolerability Continuation Study of Intracerebroventricular Administration of sNN0029 to Patients With Amyotrophic Lateral Sclerosis. U.S. National Institutes of Health.
8	Phase I trial of repeated intrathecal autologous bone marrow-derived mesenchymal stromal cells in amyotrophic lateral sclerosis. Stem Cells Transl Med. 2015 Jun;4(6):590-7.
9	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033814)
10	Dynamic expression of the mouse orthologue of the human amyotropic lateral sclerosis associated gene C9orf72 during central nervous system development and neuronal differentiation.J Anat. 2016 Dec;229(6):871-891. doi: 10.1111/joa.12526. Epub 2016 Aug 1.
11	Motor neuron disease due to neuropathy target esterase mutation: enzyme analysis of fibroblasts from human subjects yields insights into pathogenesis.Toxicol Lett. 2010 Nov 10;199(1):1-5. doi: 10.1016/j.toxlet.2010.06.020. Epub 2010 Sep 17.
12	The clinical and radiological profile of primary lateral sclerosis: a population-based study.J Neurol. 2019 Nov;266(11):2718-2733. doi: 10.1007/s00415-019-09473-z. Epub 2019 Jul 19.
13	Spastin mutations in sporadic adult-onset upper motor neuron syndromes.Ann Neurol. 2005 Dec;58(6):865-9. doi: 10.1002/ana.20652.
14	Compound heterozygote mutations in SPG7 in a family with adult-onset primary lateral sclerosis. Neurol Genet. 2016 Mar 3;2(2):e60. doi: 10.1212/NXG.0000000000000060. eCollection 2016 Apr.
15	A novel ALS2 splice-site mutation in a Cypriot juvenile-onset primary lateral sclerosis family. Neurology. 2009 Jan 6;72(1):28-32. doi: 10.1212/01.wnl.0000338530.77394.60.
16	Novel FIG4 mutations in Yunis-Varon syndrome.J Hum Genet. 2013 Dec;58(12):822-4. doi: 10.1038/jhg.2013.104. Epub 2013 Oct 3.
17	Impairment of mitochondrial anti-oxidant defence in SOD1-related motor neuron injury and amelioration by ebselen. Brain. 2006 Jul;129(Pt 7):1693-709. doi: 10.1093/brain/awl118. Epub 2006 May 15.