The Institute of Cancer Research, CRT and Astex to discover and develop novel drug candidates

Astex Pharmaceuticals, Inc (NASDAQ: ASTX), a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics, Cancer Research Technology Limited (CRT) and The Institute of Cancer Research, London, have initiated a collaboration to discover and develop drug candidates targeting an undisclosed epigenetic target in a blood cancer with high unmet medical need.
The collaboration combines Astex's world-renowned fragment-based drug discovery platform and epigenetic drug development experience with the expertise in blood cancer biology at The Institute of Cancer Research (ICR) and proven success in drug discovery at the Cancer Research UK Cancer Therapeutics Unit at the ICR.
Dysregulated epigenetic mechanisms are now understood to underlie a variety of cancer types, and have been successfully targeted by the first generation of epigenetic anticancer drugs. In some cases, specific epigenetic mutational events can be linked to disease etiology, providing an opportunity to develop highly targeted personalised medicines and associated companion diagnostics that will ultimately improve survival and reduce side effects.
"We are delighted to be entering into this new collaboration with the ICR and CRT on a key epigenetics target," said Harren Jhoti, PhD, president of Astex Pharmaceuticals. "This new partnership builds on the highly successful collaboration which Astex entered into with the ICR and CRT in 2003 on another cancer target, PKB/Akt. That collaboration led to the discovery of two clinical candidates, the first of which, AZD5363, was taken into Phase I by our partner AstraZeneca in early 2011 and the second of which, AT13148, is being prepared to be taken into Phase 1 under our development partnership with Cancer Research UK. "
Professor Paul Workman, director of the Cancer Research UK Cancer Therapeutics Unit at The Institute of Cancer Research, said: "ICR scientists are pioneers at unravelling blood cancer drug targets, which others have considered challenging to drug effectively. We have a very strong track record of designing drugs to attack challenging biological targets and bringing them into clinical trial, and given Astex's complementary expertise, we are very excited about the potential of this collaboration."
Dr Phil L'Huillier, director of business management at CRT, said: "Putting in place this collaboration between the Cancer Research UK-funded drug discovery team at the ICR and Astex provides a powerful route to identify drug candidates for this promising new target.
"The deal will ensure that the research programme benefits from the necessary investment to progress the research to its full potential while building on the validation and assay development work that has been carried out at the ICR and funded by Cancer Research UK and others.
"We hope that this research will lead to the development of new drugs to ultimately improve survival for cancer patients."

BCAA supplementation may treat autism and/or epilepsy

An international team of researchers, led by scientists at the University of California, San Diego and Yale University schools of medicine, have identified a form of autism with epilepsy that may potentially be treatable with a common nutritional supplement.
The findings are published in the September 6, 2012 online issue of Science.
Roughly one-quarter of patients with autism also suffer from epilepsy, a brain disorder characterized by repeated seizures or convulsions over time. The causes of the epilepsy are multiple and largely unknown. Using a technique called exome sequencing, the UC San Diego and Yale scientists found that a gene mutation present in some patients with autism speeds up metabolism of certain amino acids. These patients also suffer from epileptic seizures. The discovery may help physicians diagnose this particular form of autism earlier and treat sooner.

The researchers focused on a specific type of amino acid known as branched chain amino acids or BCAAs. BCAAs are not produced naturally in the human body and must be acquired through diet. During periods of starvation, humans have evolved a means to turn off the metabolism of these amino acids. It is this ability to shut down that metabolic activity that researchers have found to be defective in some autism patients.
"It was very surprising to find mutations in a potentially treatable metabolic pathway specific for autism," said senior author Joseph G. Gleeson, MD, professor in the UCSD Department of Neurosciences and Howard Hughes Medical Institute investigator. "What was most exciting was that the potential treatment is obvious and simple: Just give affected patients the naturally occurring amino acids their bodies lack."
Gleeson and colleagues used the emerging technology of exome sequencing to study two closely related families that have children with autism spectrum disorder. These children also had a history of seizures or abnormal electrical brain wave activity, as well as a mutation in the gene that regulates BCAAs. In exome sequencing, researchers analyze all of the elements in the genome involved in making proteins.

In addition, the scientists examined cultured neural stem cells from these patients and found they behaved normally in the presence of BCAAs, suggesting the condition might be treatable with nutritional supplementation. They also studied a line of mice engineered with a mutation in the same gene, which showed the condition was both inducible by lowering the dietary intake of the BCAAs and reversible by raising the dietary intake. Mice treated with BCAA supplementation displayed improved neurobehavioral symptoms, reinforcing the idea that the approach could work in humans as well.
"Studying the animals was key to our discovery," said first author Gaia Novarino, PhD, a staff scientist in Gleeson's lab. "We found that the mice displayed a condition very similar to our patients, and also had spontaneous epileptic seizures, just like our patients. Once we found that we could treat the condition in mice, the pressing question was whether we could effectively treat our patients."
Using a nutritional supplement purchased at a health food store at a specific dose, the scientists reported that they could correct BCAA levels in the study patients with no ill effect. The next step, said Gleeson, is to determine if the supplement helps reduce the symptoms of epilepsy and/or autism in humans.
"We think this work will establish a basis for future screening of all patients with autism and/or epilepsy for this or related genetic mutations, which could be an early predictor of the disease," he said. "What we don't know is how many patients with autism and/or epilepsy have mutations in this gene and could benefit from treatment, but we think it is an extremely rare condition."

Kellie Pickler Shaves Head For Breast Cancer Pal

Country star Kellie Pickler is causing quite a buzz today after shaving off all her hair.

However, it's not a new look she's trying out, or a cry for help like Britney Spears' stunt back in 2007. It's quite the opposite actually.

She lost her locks as a show of solidarity to her best childhood friend, Summer Miller, who is battling breast cancer and starts chemotherapy tomorrow. Pickler refers to Miller as her "sister" and decided to undergo the hair buzzing yesterday in Nashville alongside Miller, who received her diagnosis this past June.

Pickler alluded to the big reveal of her new hairless self on her Twitter yesterday tweeting, "It's been a great life-changing day." She followed it up an hour later with a tweet stating, "Be sure to watch "Good Morning America" today morning (Sept 5th). You won't want to miss this!!! ;)"

Pickler sent us this exclusive video of the head shaving in action. She explained that Summer is only 35, and in addition to helping her friend through a tough time, she wanted to spread the message that early detection is key.

"Cancer does not discriminate," Pickler said in a statement to ABC News. "If this compels even one person to change their mentality toward waiting until the age of 40 for their mammogram, then it will be worth it," Miller added.