Hideshi Kawakami Talks About His Work With ALS

Fast Breaking Papers Commentary, June 2011

Hideshi Kawakami

Article: Mutations of optineurin in amyotrophic lateral sclerosis


Authors: Maruyama, H, et al.
Journal: NATURE
Volume: 465, Issue: 7295, Page: 223-U109, Year: MAY 13 2010
* Hiroshima Univ, Dept Epidemiol, Res Inst Radiat Biol & Med, Hiroshima 7348553, Japan.
* Hiroshima Univ, Dept Epidemiol, Res Inst Radiat Biol & Med, Hiroshima 7348553, Japan.
(Addresses have been truncated)

Hideshi Kawakami talks with ScienceWatch.com and answers a few questions about this month's Fast Breaking Paper paper in the field of Multidisciplinary.


SW: Why do you think your paper is highly cited?

The paper presents optineurin as a novel causative gene of familial amyotrophic lateral sclerosis (ALS). Optineurin is also related to sporadic and other familial ALS. In addition, it shows the possibility of inhibitors of NF-kappa B as a drug for ALS.

SW: Does it describe a new discovery, methodology, or synthesis of knowledge?

Yes, it describes the new findings of a familial ALS gene.

SW: Would you summarize the significance of your paper in layman's terms?

"The establishment of optineurin-mutated ALS models will reveal the new findings of the disease mechanism and promote the development of new drugs that cure or at least delay the progression of ALS."

ALS is a fetal disease. The patients without the respiratory support will die in five years. Optineurin shows not only mutation of the gene in ALS, but also abnormality of the protein in other genetic and sporadic ALS. Inhibitors of NF-kappa B and optineurin modulators may be used for ALS treatment and be able to delay the disease progression.

SW: How did you become involved in this research, and how would you describe the particular challenges, setbacks, and successes that you've encountered along the way?

I have been working on neurodegenerative diseases, particularly ataxia and Parkinson’s disease, since the identification of the gene mutation for Machado-Joseph disease, a triplet repeat disease, in 1994. In 2006, I moved to this institute, and focused on the gene of familial ALS, because SOD1 gene was the only known gene causing classical ALS and genes for 80% of familial ALS patients were unknown.

ALS patients die relatively soon after the diagnosis of the disease and it is difficult to collect the large dominant inheritance family for linkage analysis. Thus, we focused on the recessive ALS families and analyzed them by homozygote mapping using single nucleotide polymorphism (SNP). High density SNPs can show the homozygote regions directly in the genome. Homozygote mapping can detect a recessive gene even in a few members of the family.

SW: Where do you see your research leading in the future?

We hope to establish optineurin-mutated ALS models.

Do you foresee any social or political implications for your research?

The establishment of optineurin-mutated ALS models will reveal the new findings of the disease mechanism and promote the development of new drugs that cure or at least delay the progression of ALS.End

Hideshi Kawakami M.D. & Ph.D.
Professor
Department of Epidemiology
Research Institute for Radiation Biology & Medicine
Hiroshima University
Hiroshima, Japan

KEYWORDS: OPTINEURIN, MUTATIONS, AMYOTROPHIC LATERAL SCLEROSIS, OPEN-ANGLE GLAUCOMA, MYOSIN VI, PROTEIN, GENE, EXPRESSION, COMPLEX, NEMO.

 
 

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