Daily Archives: January 12, 2015

An international research team finds a link between retinal degeneration and lipid metabolism

IMAGE:Dr. Robert Koenekoop examines a child's eyes and vision at the McGill Ocular Genetics Laboratory. view more

Credit: McGill University Health Centre

This news release is available in French.

Finding genes for retinal degenerations has immediate benefits for people living with blindness and vision loss, their families, and their physicians. Establishing a genetic cause confirms the clinical diagnosis at the molecular level, helps predict the future visual prognosis, suggests therapies, and allows some patients to join clinical trials. While more than 200 genes for retinal degenerations have been identified, approximately 40-50% of cases remain a mystery.

When 11 year old Naomi Lalandec walked into Dr. Robert Koenekoop's clinic at the Montreal Children's Hospital of the McGill University Health Centre (MUHC) with blindness and dwarfism due to Oliver McFarlane Syndrome (OMS), her unknown mutation sparked an international gene hunt. Comparing her genome to others with OMS and Leber congenital amaurosis (LCA), another form of childhood blindness, uncovered a new gene that is critical for vision. What makes this breakthrough exceptional is that it opens up new treatment avenues for OMS and LCA and potentially other retinal degenerative diseases.

"It was like finding a needle in a haystack," said Dr. Koenekoop, who is also a researcher at the Research Institute of the MUHC and a Professor of Human Genetics, Paediatric Surgery and Ophthalmology at McGill University. "It was so obvious to all of us that this was big; a new gene, a possible new disease pathway, a new treatment avenue." With ongoing support from the Foundation Fighting Blindness (FFB), Canada's largest charity supporting vision research, Dr. Koenekoop has spent more than a decade searching for genes linked to blindness. This search brought together an international team of scientists, including Dr. Michel Cayouette at the Institut de recherches cliniques de Montral (IRCM), Dr. Doris Kretzschmar at the Oregon Health and Science University, Dr. Jacek Majewski from the McGill University and Gnome Qubec Innovation Centre and more than 30 others from around the world. Together, the team identified mutations in the PNPLA6 gene in families with retinal degeneration. This is the 20th gene associated with LCA and the first associated with OMS.

Although we've known about the PNLPA6 gene for more than 45 years, no one had identified that mutations in this gene can lead to retinal degeneration - until now. To better understand the role of this gene, the team studied how it functions in fruit flies. They learned that the PNPLA6 gene is expressed and located in photoreceptors (which are the light-sensing cells in the eye) and that mutating the gene causes photoreceptors to die.

To determine what PNPLA6 was doing in photoreceptors, the team did a variety of experiments. They observed that some lipids were elevated in fruit flies with the PNPLA6 mutation, which led them to conclude that PNPLA6 affects phospholipid metabolism. Phospholipids are located in our cell membranes where they influence the membrane's shape and functioning. They also influence how cells communicate with each other by determining the signals that are able to pass through cell membranes. When phospholipids stop doing what they are supposed to do, important signals get lost and cells can no longer maintain their structures or respond to their environment.

This novel insight about the role of phospholipid metabolism in photoreceptor biology paves the way for new sight-saving treatments. These potentially game-changing results were published on January 9, 2015 in the prestigious journal Nature Communications.

See original here:
Genetic discovery about childhood blindness paves the way for new treatments

By RTT News, January 12, 2015, 08:18:00 AM EDT

(RTTNews.com) - Seattle Genetics, Inc. ( SGEN ) and Bristol-Myers Squibb Co. ( BMY ) Monday said they have entered into a clinical trial collaboration agreement to evaluate the investigational combination of Seattle Genetics' antibody-drug conjugate, or ADC, Adcetris (brentuximab vedotin) and Bristol-Myers Squibb's immunotherapy Opdivo (nivolumab) in two planned Phase 1/2 clinical trials.

The first trial will evaluate the combination of Adcetris and Opdivo as a potential treatment option for patients with relapsed or refractory Hodgkin lymphoma or HL, and the second trial will focus on patients with relapsed or refractory B-cell and T-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma.

Adcetris is an ADC directed to CD30, a defining marker of classical HL, which combines the targeting ability of a monoclonal antibody with the potency of a cell-killing agent. Opdivo is a human programmed death receptor-1 blocking antibody that binds to the PD-1 receptor expressed on activated T-cells.

The studies are expected to begin in 2015, with Seattle Genetics conducting the HL trial and Bristol-Myers Squibb conducting the NHL trial.

Adcetris is approved in relapsed HL and systemic anaplastic large cell lymphoma, but is not currently approved for the treatment of relapsed, transplant eligible HL or for the treatment of other types of NHL. Opdivo is currently not approved for the treatment of lymphoma.

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Seattle Genetics, Bristol-Myers Report Clinical Trial Collaboration