Fruitfly Model Of A Neuropathic Disease Demonstrates Novel Role For Proteins In The Family Of Atyr P

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15th July 2009, 10:06am - Views: 697


Fruitfly Model of a Neuropathic Disease Demonstrates Novel Role for Proteins in the Family of aTyr

Pharma's Product Class

SAN DIEGO, July 15 /PRNewswire-AsiaNet/ --

          aTyr Pharma's Naturally Occurring Resected Proteins are Novel


    Research published in the June 26, 2009 edition of Proceedings of National Academy of Sciences provides

further evidence for novel roles of tRNA synthetases in disease, validating the therapeutic potential for aTyr

Pharma's new class of naturally occurring protein agents. The aminoacyl tRNA synthetases are universal and

essential components of protein synthesis machinery found in all organisms, but human synthetases have naturally

occurring resected variants with potent cell signaling activities that are vital to normal functioning of humans. aTyr

Pharma's proprietary product generating engine consists of these resected proteins (resectins) of human aminoacyl

tRNA synthetases with cell signaling activities distinct from the protein synthesis activities. In this recently published

study, a model of a human neuropathy was created in the fruit fly (Drosophila) by introducing mutations in the

tyrosyl-tRNA synthetase which correspond to disease associated mutations in humans. These dominant mutations

do not cause a loss in the protein synthesis activity, indicating that the neuropathy arises from distinct activities of

this tRNA synthetase. This work provides further proof of noncanonical roles for tRNA synthetases in human


    The large team of scientists on the study included Professors Paul

Schimmel and Xiang-Lei Yang, scientific co-founders of aTyr Pharma, and

Leslie Nangle, Director of Research at aTyr Pharma, and was led by Albena

Jordanova of the University of Antwerp. Other scientists contributing to this

paper are from the University of Antwerp, Universiteit Leuven, and Florida

Atlantic University. Professor Paul Schimmel of The Scripps Research

Institute describes the significance of the work. "Charcot-Marie-Tooth (CMT)

is one of the most common inherited neurological disorders, with typical

symptoms usually emerging in early adulthood, including loss of muscle mass,

pain and sensitivity, foot deformations and difficulties in walking. Human

genome sequencing revealed that some CMT patients have mutations in a gene

encoding tyrosyl-tRNA synthetase. While tRNA synthetases play an essential

role in protein synthesis in all forms of life, these dominant mutations in

CMT patients did not seem to manifest the disease through disruption of those

protein synthesis activities. When the mutations found in humans are

introduced into the Drosophila genome, the flies develop neurological defects

that correspond to CMT in humans. While we are still trying to understand how

mutations in the tRNA synthetase gene disrupt the neurological system of a

complex organism, this study showed that there are neurological functions

encoded in this gene."

    According to Jeff Watkins, CEO of aTyr Pharma, "In the past few years,

Professor Schimmel has discovered a whole new area of biology: novel

signaling functions for naturally occurring proteins resected from ancient

proteins such as tRNA synthetases. This work in Drosophila illustrates a

surprising disease-causing role for tRNA synthetases that is not related to

the well-studied protein synthesis activities of these enzymes. Instead, in

humans and this fruit fly model, the tyrosyl-tRNA synthetase gene encodes a

distinct function involved in the complex neurobiology of an organism. These

novel activities are seen for other members of the tRNA synthetases family as

well, and aTyr Pharma's portfolio capitalizes on this new area of biology by

using these naturally occurring resectins with novel signaling activities to

treat a wide variety of diseases, such as inflammation, automimmune,

hematopoietic and metabolic disorders."

Science Research ATyr Pharma 2 image

    The PNAS publication can be accessed at:

    SOURCE:  aTyr Pharma

    CONTACT: Cheryl Quinn

             Director of Business Development of aTyr Pharma



   or media, Jennifer James of Alta Partners




             for aTyr Pharma

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