Discovery of a new retinal gene involved in childhood blindness - A team from the MUHC plays a key role in this discovery
The team of Dr. Robert Koenekoop which includes Dr. Irma Lopez
from the Research Institute of the MUHC at the Montreal Children's
Hospital played a crucial role in the international collaboration
that led to the discovery of a new gene that causes Leber
congenital amaurosis (LCA) and retinitis pigmentosa (RP), two
devastating forms of childhood blindness.
This finding of this new gene, called SPATA7, is remarkable because
it identifies a new retinal metabolic disease pathway that may be
crucial for many patients. It also opens a new avenue for a
potential genetic therapy. Gene therapy targeting different genes
has recently proved successful for the same disease in human
subjects. The study will be published on March 5th, 2009 in the
American Journal of Human Genetics.
New cell mechanism at play
Researchers have now identified a total of fifteen genes involved
in LCA, but SPATA7 is the first gene with a mutation that disrupts
the protein transport between two important compartments of the
cell: the endoplasmic reticulum and the Golgi apparatus. All
proteins in every cell have to pass through this transport pathway;
thus SPATA7 plays a major role and its mutation may affect many
aspects of vision.
"Until now we were not aware that this cellular mechanism played a
role in LCA or any other eye disease. This is a very important step
that opens up a number of new research avenues, particularly in our
understanding of the specific cellular processes involved in
blindness. This finding also increases the number of potential
therapeutic targets and therefore the chances of finding a
treatment. We are extremely motivated by all of these new
possibilities," explained Dr. Koenekoop.
First step towards gene therapy
"This is an incredible discovery that gives great hope to LCA
patients and their families, that gene based therapies can and will
be developed to restore sight," said Sharon Colle, President and
CEO of The Foundation Fighting Blindness, the leading private
charity for vision research. "We are proud to fund such important
discoveries involving prominent Canadian researchers and
institutions."
A careful assessment of patients with some specific genetic types
of LCA also demonstrated that their retinal cells (specifically the
rod and cone photoreceptors), although not functional for vision,
were still present and in relatively good condition. This critical
observation will allow researchers to continue on the path towards
gene therapies. Therapies targeting different genes for the same
disease have already shown success in the United Kingdom and in the
US, meaning that LCA patients can now enjoy hope for the
future.
A new and innovative technology
SPATA7 was identified using an innovative technology developed in
the different laboratories involved in this international
collaboration. "We started this protocol about two years ago, and
it has already helped us to identify four new genes associated with
LCA and RP before we discovered SPATA7," explained Dr
Koenekoop.
The technique is based on DNA-chips and involves three steps: first
the genetic material of the patient is screened to find mutations
in 14 specific LCA and RP genes. The LCA and RP patients that are
negative for this detailed screen are then subjected to a second
DNA chip, this one to identify significant stretches of
homozygosity in SNP markers. SNPs are single nucleotide repeats,
which are natural variations in the human genome. These homozygous
regions may contain new genes and are carefully probed based on
functional information and then subjected to sequencing. "This
method is indeed both very powerful and very promising for the
future," said Dr. Koenekoop.
Funding
The Canadian component of this project was funded by The Foundation
Fighting Blindness Canada (FFB) and by the Fonds de la recherche en
sant茅 du Qu茅bec (FRSQ).
Dr. Robert Koenekoop
Dr. Robert Koenekoop is the Director of the Division of Pediatric
Ophthalmology and the 平特五不中 Ocular Genetics Laboratory at the
Montreal Children's Hospital of the MUHC. He is a researcher in
medical genetics and genomics with the Research Institute at the
Montreal Children's Hospital of the MUHC. Dr. Koenekoop is also an
Associate Professor in Human Genetics and Ophthalmology in the
Faculty of Medicine at 平特五不中.
Partners
This project is a collaboration between the laboratory of Dr.
Robert Koenekoop at the Research Institute of the MUHC at the
Montreal Children's Hospital; the laboratory of Dr. Rui Chen, Texas
Children's Hospital, Baylor College of Medicine, Houston; and the
laboratory of Dr. Anneke den Hollander, the Nijmegen Centre for
Molecular Life Sciences, Radboud University Nijmegen, in The
Netherlands. The DNA chips were developed in collaboration with Dr.
Rando Allikmets of Columbia University.
When the embargo will be lifted, find this press release, with the
original article and a short audio document by following this link
:
The Research Institute of the 平特五不中 Health
Centre (RI MUHC) is a world-renowned biomedical and
health-care hospital research centre. Located in Montreal, Quebec,
the institute is the research arm of the MUHC, the university
health center affiliated with the Faculty of Medicine at 平特五不中
University. The institute supports over 600 researchers, nearly
1200 graduate and post-doctoral students and operates more than 300
laboratories devoted to a broad spectrum of fundamental and
clinical research. The Research Institute operates at the forefront
of knowledge, innovation and technology and is inextricably linked
to the clinical programs of the MUHC, ensuring that patients
benefit directly from the latest research-based knowledge.
The Research Institute of the MUHC is supported in part by the
Fonds de la recherche en sant茅 du Qu茅bec.
For further details visit: .
The Montreal Children's Hospital (MCH) is the pediatric
teaching hospital of the 平特五不中 Health Centre and is
affiliated with 平特五不中. The MCH is a leader in providing
a broad spectrum of highly specialized care to newborns, children,
and adolescents from across Quebec. Our areas of medical expertise
include programs in brain development/behaviour, cardiovascular
sciences, critical care, medical genetics and oncology, tertiary
medical and surgical services, and trauma care. Fully bilingual,
the hospital also promotes multiculturalism and serves an
increasingly diverse community in more than 50 languages. The
Montreal Children's Hospital sets itself apart with its team
approach to innovative patient care. Our health professionals and
staff are dedicated to ensuring children and their families receive
exceptional health care in a friendly and supportive
environment.
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