Juvenile Amyotrophic Lateral Sclerosis

TY - CHAP

T1 - Juvenile Amyotrophic Lateral Sclerosis

AU - Sreedharan, Jemeen

AU - Brown, Robert H.

PY - 2014/12/3

Y1 - 2014/12/3

N2 - Juvenile ALS is a broad diagnostic term that encompasses a core entity of upper and lower motor neuron diseases with, in some cases, a wide realm of additional clinical features. The last 10-15 years have witnessed an unprecedented proliferation of information about the molecular genetics of disorders that can be described as jALS; in many respects, the enormous genetic diversity mirrors and anticipates the clinical heterogeneity. At this point, it is difficult to find unifying molecular themes in the diverse set of jALS genes, a quandary that reflects in part our relatively poor understanding of the genesis of this type of neurodegenerative disorder. One anticipates that the exploration of the molecular biology of jALS will ultimately also provide insight into the nature of adult-onset ALS. That the two can converge is clear in the example of jALS caused by FUS mutations. In the long term, one also hopes that new insights into the molecular pathology of jALS will provide targets for therapy. Moreover, independently of the full delineation of the molecular pathways, strategies such as gene silencing and gene replacement may prove beneficial for cases arising respectively from gain-of-function (dominant) and loss-of-function (recessive) mutations. Recent early successes in gene replacement (e.g. lipoprotein lipase deficiency mediated by adeno-associated virus) and exon skipping for muscular dystrophy (e.g. Sarepta Inc. eteplirsen trial in Duchenne muscular dystrophy) permit cautious optimism that meaningful therapies will be possible for inherited forms of jALS.

AB - Juvenile ALS is a broad diagnostic term that encompasses a core entity of upper and lower motor neuron diseases with, in some cases, a wide realm of additional clinical features. The last 10-15 years have witnessed an unprecedented proliferation of information about the molecular genetics of disorders that can be described as jALS; in many respects, the enormous genetic diversity mirrors and anticipates the clinical heterogeneity. At this point, it is difficult to find unifying molecular themes in the diverse set of jALS genes, a quandary that reflects in part our relatively poor understanding of the genesis of this type of neurodegenerative disorder. One anticipates that the exploration of the molecular biology of jALS will ultimately also provide insight into the nature of adult-onset ALS. That the two can converge is clear in the example of jALS caused by FUS mutations. In the long term, one also hopes that new insights into the molecular pathology of jALS will provide targets for therapy. Moreover, independently of the full delineation of the molecular pathways, strategies such as gene silencing and gene replacement may prove beneficial for cases arising respectively from gain-of-function (dominant) and loss-of-function (recessive) mutations. Recent early successes in gene replacement (e.g. lipoprotein lipase deficiency mediated by adeno-associated virus) and exon skipping for muscular dystrophy (e.g. Sarepta Inc. eteplirsen trial in Duchenne muscular dystrophy) permit cautious optimism that meaningful therapies will be possible for inherited forms of jALS.

KW - ALS

KW - Alsin

KW - Brown-Vialetto-Van Laere (BVVL) syndrome

KW - Degenerative motor neuron disease

KW - Distal hereditary motor neuropathy (dHMN)

KW - Distal SMA

KW - Hereditary spastic paraparesis (HSP)

KW - Intestinal riboflavin transporter

KW - JALS

KW - Juvenile amyotrophic lateral sclerosis

KW - Madras Motor Neuron Disease (MMND)

KW - Senataxin

KW - SLC52A1

KW - SLC52A2

KW - SLC52A3

KW - SPG (Spastic ParapleGia)

UR - http://www.scopus.com/inward/record.url?scp=84944615874&partnerID=8YFLogxK

U2 - 10.1016/B978-0-12-417044-5.00009-3

DO - 10.1016/B978-0-12-417044-5.00009-3

M3 - Chapter

SN - 9780124170445

SP - 146

EP - 159

BT - Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician's Approach

PB - Elsevier Inc.

ER -