PTC124 Targets Nonsense Mutations; Addresses Underlying Cause of Genetic
Disorders and Restores Protein Function
SOUTH PLAINFIELD, N.J., April 23 /PRNewswire/ -- New preclinical data
published online in the current edition of the journal Nature show that
PTC124, an investigational new drug designed to bypass nonsense mutations,
was efficacious in a preclinical model of Duchenne muscular dystrophy
(DMD). It is estimated that approximately 13 percent of the cases of DMD
are due to nonsense mutations. PTC Therapeutics, Inc., which discovered and
is developing PTC124, has catalogued over 1,800 distinct genetic disorders
where nonsense mutations are the cause of the disease in a significant
percentage of patients. Nonsense mutations inactivate gene function and are
known to cause anywhere from five to 70 percent of the individual cases of
most inherited diseases, such as cystic fibrosis (10%) and Hurler's
syndrome (70%).
(Logo: http://www.newscom.com/cgi-bin/prnh/20010919/PTCLOGO )
"We are pleased that the Nature paper offers an opportunity for us to
describe our novel approach to regulating post-transcriptional control
processes," said Stuart W. Peltz, Ph.D., President and Chief Executive
Officer of PTC Therapeutics. "As these preclinical data demonstrate, the
broad potential of PTC124 lies in its specificity and unique mechanism of
action, which has the potential to address the underlying cause of a broad
range of genetic disorders due to nonsense mutations."
Dr. Peltz continued, "In addition to the ongoing Phase 2 clinical
trials of PTC124 in cystic fibrosis and Duchenne muscular dystrophy, we are
evaluating PTC124 in a number of additional genetic disorders."
Post-transcriptional control processes are the cellular regulatory
events that take place after an RNA molecule is copied from DNA. These
processes are critical to proper cellular function and provide an
opportunity for therapeutic intervention through the modulation of protein
levels.
Genetic disorders, such as DMD and cystic fibrosis (CF) are caused by
genetic alterations, known as mutations. By targeting a specific type of
genetic alteration -- nonsense mutations -- PTC124 bypasses the defect and
leads to the restoration of a functional protein. The Nature paper
highlights the data obtained from PTC's work in a mouse model of DMD in
which a nonsense mutation precludes the production of dystrophin. Loss of
functional dystrophin, an important muscle protein involved in maintaining
the strength of muscle fibers, results in DMD. The data demonstrate that
PTC124 allows dystrophin to be made in cells in which it was previously
absent, to be delivered to the proper cellular location, and to induce
restoration of muscle function. In addition to the studies described in the
Nature paper, PTC has demonstrated in preclinical studies that PTC124
restores the presence of the missing protein in CF caused by nonsense
mutations. Similar to the effect in DMD, PTC124 induces production of CFTR
(the missing protein in CF).
The paper entitled, "PTC124 targets genetic disorders caused by
nonsense mutations" is available in an advanced online publication of
Nature on Sunday, April 22nd (http://www.nature.com). This publication is
the result of collaborative efforts between PTC Therapeutics, the
University of Pennsylvania School of Medicine, and the University of
Massachusetts Medical School.
About PTC124
PTC124 is an orally delivered investigational new drug in Phase 2
clinical development for the treatment of genetic disorders due to nonsense
mutations. Nonsense mutations are single-point alterations in the genetic
code that introduce premature stop codons in RNA, which halt the
translation process, producing a shortened, non-functional protein. PTC124
has demonstrated activity in preclinical genetic disease models harboring
nonsense mutations, allowing the readthrough of premature stop codons and
the restoration of the production of full-length, functional proteins. In
Phase 1 clinical trials, PTC124 was generally well tolerated, achieved
target plasma concentrations that have been associated with activity in
preclinical models, and did not induce readthrough of normal stop codons.
PTC is currently conducting Phase 2 clinical trials of PTC124 in
nonsense-mutation-mediated cystic fibrosis and Duchenne muscular dystrophy.
The FDA has granted PTC124 Fast-Track designations and Orphan Drug
designations for the treatment of CF and DMD due to nonsense mutations.
PTC124's development is supported by grants from the Muscular Dystrophy
Association (MDA), Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT),
Parent Project Muscular Dystrophy (PPMD), FDA's Office of Orphan Products
Development (OOPD), the National Institutes of Health, and by General
Clinical Research Center grants from the National Center for Research
Resources (NCRR).
About PTC Therapeutics, Inc.
PTC is a biopharmaceutical company focused on the discovery and
development of orally administered, proprietary, small-molecule drugs that
target post-transcriptional control processes. Post-transcriptional control
processes regulate the rate and timing of protein production and are of
central importance to proper cellular function. PTC's internally-discovered
pipeline addresses multiple therapeutic areas, including genetic disorders,
oncology, and infectious diseases. In addition, PTC has developed
proprietary technologies and extensive knowledge of post-transcriptional
control processes that it applies in its drug discovery and development
activities, including the Gene Expression Modulation by Small-molecules
(GEMS) technology platform, which has been the basis for collaborations
with leading pharmaceutical and biotechnology companies such as Pfizer, CV
Therapeutics, and Schering-Plough.
SOURCE PTC Therapeutics, Inc.
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Related links:
http://www.ptcbio.com
http://www.nature.com
Photo Notes:
NewsCom: http://www.newscom.com/cgi-bin/prnh/20010919/PTCLOGO
/ AP Archive: http:
CONTACT:
Jane Baj of PTC Therapeutics, Inc.,
+1-908-222-7000, Ext. 167, jbaj@ptcbio.com, or Sheryl Seapy of
Pure Communications, +1-949-608-0841,
sheryl@purecommunicationsinc.com, for PTC Therapeutics, Inc.
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