LM-030 for Netherton Syndrome

Disease Description

Netherton Syndrome was first described by Comel in 1949(1) and Netherton in 1958(2). It is a severe autosomal recessive disease characterized by congenital erythroderma, “bamboo hair” and abnormality in the immune system(3). Netherton Syndrome in newborns can be life-threatening due to missing skin protection that leads to severe dehydration, hypernatremia, hypothermia, gross weight loss and sepsis. Failure to thrive is common in childhood as a result of chronic erythroderma, persistent cutaneous infection, malnutrition and metabolic disorders(4,5). The severity of the skin abnormality in older patients can fluctuate over time. Most Netherton Syndrome patients are also inflicted with immune system-related disorders such as food allergies and asthma.

Prevalence

Though the prevalence of Netherton Syndrome is not well documented, it has a reported prevalence of 1-9 per 1,000,000(6).

Current Treatment

There are no approved products for treating Netherton Syndrome. Current treatments are limited to symptom relief with marginal efficacy and unwanted side effects.

Cause and Pathogenesis

Netherton Syndrome is caused by mutations in the SPINK5 gene that encodes a serine peptidase inhibitor, Lympho-epithelial Kazal-type-related inhibitor (LEKTI)(1). The loss of LEKTI leads to dysregulation of epidermal proteases and severe skin barrier impairment. Kallikrien-related peptidases, which are inhibited by LEKTI, are reported to play major roles in Netherton Syndrome pathology(7,8). Multiple efforts have been spent on targeting the KLKs for treating Netherton Syndrome.

References

1. Comel M, Dermatology 1949; 98: 133-136

2. Netherton EW, Arch Dermatol. 1958; 78: 483-487

3. Bitoun E et al, Journal of Investigative Dermatology 2002; 118(2): 352-361

4. Jones SK et al, Br. J. Dermatol. 1986; 114: 741-743

5. Judge MR et al, Br. J. Dermatol. 1994; 131: 615-621

6. Orphanet

7. Kasparek P et al, PLOS Genetics 2017, 13(1)

8. Caubet C et al, Journal of Investigative Dermatology 2004; 122: 1235-1244

9. The image is reproduced with permission from JAMA Dermatology, 1999, 135 (7): 823-832.       

Copyright©1999 American Medical As sociation. All rights reserved.

LM-030 is a topical treatment in development for Netherton Syndrome. It has completed extensive preclinical testings and demonstrated positive proof of concept in a Phase IIa study for Netherton Syndrome

 

Treating Orphan Diseases With Few or No Therapeutic Options.

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Taipei, Taiwan

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