Genome British Columbia

Genome British Columbia

September 24, 2009 09:00 ET

Genome British Columbia: Genomic Research Will Help Provide Alternative Treatments to Patients With Iron Overload

VANCOUVER, BRITISH COLUMBIA--(Marketwire - Sept. 24, 2009) - Genome British Columbia -

While most people are familiar with anemia - or lack of iron in the blood - they are less familiar with diseases of too much iron.

Excess iron in the body, if left unchecked, can form toxic deposits in major organs leading to serious conditions including heart failure, diabetes, liver cirrhosis, arthritis, and even infertility. Iron overload can be a consequence of a genetically mutated gene known as hereditary hemochromatosis, or a consequence of red blood cell transfusions, required as life saving treatments, for patients with diseases such as thalassemia.

Patients with hemochromatosis and thalassemia both absorb too much iron from their diet which either causes or exacerbates their iron overloading to levels that are toxic.

The mutated gene for hemochromatosis is carried by 1 in 9 Canadians. Currently over 100,000 Canadians and several million people in the US have hemochromatosis, with many of these patients still undiagnosed.

"Part of the problem is that this condition of hemochromatosis will present itself in disguised ways and is often unrecognized by physicians. A patient may have arthritis, or extreme fatigue or even diabetes, but often it's not linked to the real genetic cause, which is iron overload," says Dr. Paul Goldberg of Xenon Pharmaceuticals.

Goldberg is the lead investigator on the $7.5 million project entitled Enabling Studies for a DMT1 inhibitor - A Novel Therapeutic Approach for Treatment of Iron Overload Disorders.

The research, funded by Xenon Pharmaceuticals and Genome BC will tackle the disease, by creating a small-molecule drug to block excess iron absorption at its source: directly in the gut.

Currently, hemochromatosis patients are treated with lifelong phlebotomies - invasive and sometimes painful treatments that require regular trips to the hospital or clinic to remove about half a litre of blood, allowing the patient to produce new blood with less iron.

While phlebotomies work well in many of the patients, they can be problematic, causing recipients to feel unwell for a while following the procedure. "Patients are rendered anemic temporarily so the procedure is not suitable for people with heart conditions or needle intolerance," says Goldberg. He also points out that patient compliance can be a problem with this form of treatment.

As such, Goldberg's research is focused on creating a safe and effective oral therapy as an alternative or adjunctive treatment for those affected by iron overload.

"Patients with hemochromatosis are hyper-absorbing iron he says. The drug that we are developing would block the key transporter for this excess iron uptake, known as DMT1."

Thalassemia patients may also directly benefit from the DMT1 blockers. These patients become severely iron overloaded at a young age due to the requirement for regular life saving blood transfusions and the additive complication of excessive iron absorption from their diet.

Patients who chronically receive blood transfusions are currently treated with iron chelators to control their iron levels. However chelators have severe dose limiting side effects and it remains challenging for clinicians to maintain normal iron balance in these patients. In addition, chelation therapy is extremely expensive, sometimes costing up to $50,000 per patient and may require for some patients frequent and prolonged intravenous administration.

"The Xenon drug provides an oral alternative and is being optimized for patient safety," says Dr. Simon Pimstone, President and CEO of Xenon Pharmaceuticals. "Our DMT1 blockers could lower the dosage of iron chelator drugs making them safer or could make them more effective, either way, improving patient outcomes. Our goal is to test this drug in iron overload patients within two to three years."

"Genome BC is pleased to co-support this innovative research, which may develop an innovative, safe and valuable treatment alternative to patients suffering from iron overload disorders," says Dr. Alan Winter, President and CEO of Genome BC.

About Genome BC

Founded in 2000, Genome BC works collaboratively with government, universities and industry as the catalyst for a genomics-driven life sciences cluster with significant social and economic benefits for the Province and Canada. The organization's research portfolio, over $410 million since inception, includes 74 projects and technology platforms focused on areas of strategic importance to British Columbia such as human health, forestry, fisheries, bioenergy, mining, agriculture, and the environment. Genome BC programs are funded by Genome Canada, the Provincial Government of British Columbia, Western Economic Diversification Canada and other public and private partners. For more information visit www.genomebc.ca.

NOTE TO EDITORS

Dr. Simon Pimstone and Dr. Paul Goldberg of Xenon and Dr. Gabe Kalmar of Genome BC will be available for interviews following the announcement of their project at the Life Sciences BC event: "Staying Afloat in a Sea of Economic Uncertainty: Growing a Successful Life Sciences or Cleantech Business".

Media are invited to attend. Telephone interviews and photos available on request.

Date/Time: Thursday, September 24th, 2009 at 11:45 a.m.

Place: Sutton Place Hotel, Versailles A Ballroom, 845 Burrard St., Vancouver, BC

BACKGROUND INFORMATION

Genomic research will help provide alternative treatments to patients with iron overload

PROJECT DESCRIPTION

Iron is essential to bind oxygen and transport electrons for all living organisms, but excess iron levels are toxic and can cause diabetes, liver cirrhosis, heart disease and arthritis. Over 100,000 Canadians have a genetic disease called Hereditary Hemochromatosis (HH) that results in toxic accumulation of iron.

The major goal of this research is to translate the preclinical research of iron accumulation inhibitors into clinical trials by 2010.

The only current treatment is blood-letting, or phlebotomy, which is an invasive procedure and for a subset of patients, may be an uncomfortable or deleterious treatment option. Similarly, patients with conditions including certain anemias and thalassemias who develop iron overload because of their requirement for transfusions, also absorb too much iron from their diet which exacerbates the iron overload. A safe and effective oral therapeutic would be an excellent alternative or adjuvant treatment for those affected by iron accumulation disorders. The project led by Xenon Pharmaceuticals and Dr. Paul Goldberg will determine a suitable candidate for clinical trials through testing a set of candidate drugs that prevent iron absorption in the intestine.

More on the Science

Excess iron accumulation in the body is toxic due to formation of oxygen free radicals and other noxious substances that can damage many different organs. Hereditary hemochromatosis is the most prevalent genetic disorder in Canada and causes iron accumulation because of increased iron absorption from the diet. If HH is detected early, it is treatable and reversible but most affected patients are unaware they have toxic accumulations of iron until significant tissue damage has already occurred. The current treatment for HH is phlebotomy or bloodletting. While this is effective in many patients with HH, approximately 10% of patients do not tolerate phlebotomy. A more rational and complimentary treatment targeting the root cause of the disease, excessive intestinal iron absorption, is currently being developed by Xenon.

DMT1 is the major iron transporter in the intestine and inhibition of this early step in the iron absorption pathway, it is believed will provide a treatment for HH. A group of DMT1 inhibitors have been identified and are currently being tested for efficacy and safety so that a single candidate can be selected to enter clinical trials. Phase I clinical trials will involve giving healthy volunteers single ascending doses of the inhibitor to assess potential side effects and generate early Proof of Concept results. This project will identify DMT1 inhibitors suitable for entry into Phase I clinical trials where initial safety and early proof of concept will be defined.

Another large group of patients that suffer from iron overload are people that require repeated blood transfusions because of diseases such as anemias and thalassemias. Transfusion iron-overloaded patients are treated with iron chelators to control iron excess, but this treatment can have severe side effects and is not fully effective. The underlying anemia also stimulates intestinal iron absorption exacerbating the accumulation of iron in the body; therefore decreasing iron absorption from the diet by inhibiting DMT1 may provide an adjuvant therapy for iron-overloaded transfusion recipients.

PROJECT LEADER BIOGRAPHY

Dr. Paul Goldberg

Dr. Goldberg is the Senior Director of Clinical Biology and Target Discovery at Xenon Pharmaceuticals. At Xenon, the mission is to discover, develop and commercialize innovative medicines based on genetically derived targets. Dr. Goldberg currently leads an iron metabolism project that plans to deliver improved therapeutics to patients with iron overload and other disorders of iron metabolism.

PROJECT INFORMATION

Project Title: IND Enabling Studies for a DMT1 Inhibitor - A Novel Therapeutic Approach for Treatment of Iron Overload Disorders

Project Value: $7,469,280

Project Leader: Dr. Paul Goldberg

Co-Applicants: Dr. Simon Pimstone, Dr. Michael Hayden, Dr. Michael Winther, Dr. David Goodkin, Nicola Price, Dr. Alison Brownlie

Involved Institutions: Xenon Pharmaceuticals

Technology Applications: Iron overload treatment, genetic disease treatment

About Genome BC

Founded in 2000, Genome BC works collaboratively with government, universities and industry as the catalyst for a genomics-driven life sciences cluster with significant social and economic benefits for the Province and Canada. The organization's research portfolio, over $410 million since inception, includes 74 projects and technology platforms focused on areas of strategic importance to British Columbia such as human health, forestry, fisheries, bioenergy, mining, agriculture, ethics and the environment. Genome BC programs are funded by Genome Canada, the Provincial Government of British Columbia, Western Economic Diversification Canada and other public and private partners. For more information visit www.genomebc.ca.

About Xenon

Xenon is a privately owned, clinical genetics-based drug discovery and development company engaged in developing small molecule therapies based on the genetic causes of select metabolic, neurological and cardiovascular diseases. For more information, visit www.xenon-pharma.com.

NOTE TO EDITORS

Dr. Simon Pimstone and Dr. Paul Goldberg of Xenon and Dr. Gabe Kalmar of Genome BC will be available for interviews following the announcement of their project at the Life Sciences BC event: "Staying Afloat in a Sea of Economic Uncertainty: Growing a Successful Life Sciences or Cleantech Business".

Media are invited to attend. Telephone interviews and photos available on request.

Date/Time: Thursday, September 24th, 2009 at 11:45 a.m.

Place: Sutton Place Hotel, Versailles A Ballroom, 845 Burrard St., Vancouver, BC

Contact Information