Merck & Co. has decided to continue its research collaboration with Addex Pharmaceuticals for an additional year. The partnership is focused on developing positive allosteric modulators (PAM) of the metabotropic glutamate receptor 4 (mGluR4) for the treatment of Parkinson disease and other undisclosed indications.

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The decision follows a report earlier this year from Addex that a preclinical study with an orally available mGluR4 PAM showed efficacy in an animal model of Parkinson. With the extension, Addex will recognize $1.8 million in research funding over the next 12 months in addition to the original financial terms.

As per the exclusive collaboration and license agreement announced in December 2007, Addex received $3 million up front. Since then the company has been paid two preclinical milestones of $250,000 and $500,000. Addex is eligible to receive up to $106.5 million in research, development, and regulatory milestones for the first product developed for multiple indications.

Additional milestones of up to $61 million would be payable if a second and third product are developed. Addex will also receive royalties on sales of any products resulting from this collaboration.

Glutamate, like dopamine and serotonin, is a key neurotransmitter in the human brain, an important signaling molecule involved in control of multiple brain functions ranging from motor control to mood. In Parkinson the death of dopamine-producing neurons leads to excess glutamate signaling.

Current treatments focus on dopamine-replacement strategies. Yet, most patients reach a stage where dopaminergic treatments are no longer effective. There can also be debilitating side effects with dopaminergic treatments. It is believed that selective activation of mGluR4 is one way to bypass the dopamine pathway and could correct the circuitry that modulates motor excitability via a nondopaminergic mechanism.

Research shows that mGluR4 activators could work via two distinct mechanisms to alleviate symptoms of the disease and, potentially, even slow the progression of the disease, according to Addex and Merck. mGluR4 activation triggers a compensatory mechanism that may spare or potentiate the use of dopamine-receptor activators. And mGluR4 activation may have a neuroprotective effect that helps to preserve the brain’s dopaminergic neurons.

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Addex has an mGluR5 NAM candidate called ADX10059 in Phase IIb testing for GERD and migraine prevention. The mGluR5 NAM ADX48621 has completed Phase I for levodopa-induced dyskinesia related to Parkinson. Also, Addex’ partner, Ortho-McNeil-Janssen Pharmaceuticals, is performing a Phase I study of another mGluR2 PAM, ADX71149, which has potential in anxiety and schizophrenia.

Source: GEN News

Popularity: 2% [?]

A gene long thought to be a risk factor for depression when combined with environmental stress doesn’t appear to be associated with increased depression risk after all. That’s the finding of research published in the Journal of the American Medical Association that analyzes pooled data from 14 different studies.

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A highly publicized paper published in 2003 showed that individuals with a version of a serotonin-system gene, 5-HTTLPR, who experienced more life stressful life events had greater risk of depression.

Since then, many scientists have devoted themselves to studying that gene and to research that examines the interaction between genes and environment on mental illness. One company began offering a test of the gene to measure one’s likelihood of getting depressed and clinicians have wondered if they should test their patients as well.

But the finding hadn’t been properly replicated, say the authors of the JAMA study, prompting the team to conduct the meta-analysis.

“One of the concerns of the research team that we raise [in the paper] is that this needs to be much more carefully filtered before it’s used for prime time with the public,” study author Kathleen Merikangas, referring to the genetic findings, told the Health Blog. Merikangas is a senior investigator at the National Institute of Mental Health.

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The researchers took data from 14 previously published studies, recoded and re-analyzed them according to the same criteria as the 2003 study. The results showed there was no relationship between the gene, stressful events and risk of depression, nor between the gene and depression itself.

“We do not see that there is evidence for the interaction between the serotonin transporter gene, stressful life events and depression,” Merikangas told the Health Blog. The focus on this particular gene and environment interaction “is somewhat of an oversimplification of the very complicated pathways that lead to both clinical depression and depression that is a human emotion,” she said.

Merikangas said that the research team hopes researchers will “think more carefully” about studying gene and environmental interaction.

Avshalom Caspi, a Duke professor and one of the authors of the original 2003 study, told the Health Blog in an email that the new JAMA study ignores scientific evidence that indeed shows that the carriers of the gene are excessively vulnerable to stress and “misrepresents” some other studies. Also, he said that the findings in the meta-analysis vary widely and that the quality of the individual studies varies as well.

“What is needed is not less research into gene-environment interaction … but more research of better quality, and a more thorough and thoughtful evaluation of it,” Caspi wrote in his email.

Source: The Wall Street Journal

Popularity: 4% [?]

AstraZeneca said today that it’s partnering with the Mayo Clinic and Virginia Tech to work on an experimental class of antidepressants known as triple reuptake inhibitors, or TRIs.

The drugs target three brain chemicals believed to be involved in depression — serotonin, norepinephrine and dopamine. Existing drugs target just serotonin, or serotonin and norepinephrine.

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The project announced today has yet to test a TRI in people. That puts AstraZeneca a bit behind some other drug makers. In 2007, Danish firm NeuroSearch said it was carrying out a phase-2 study on a TRI with GlaxoSmithKline. Bristol-Myers Squibb has worked with Albany Molecular Research Inc. on similar drugs, and Dov Pharmaceutical said last year it was starting a phase-2 study on a TRI.

By adding dopamine to the mix, drug makers hope to crack certain types of depression that typically don’t respond to drug treatment, including melancholic depression, Christer Köhler, vice president of global discovery research at AstraZeneca, told the Health Blog.

“We know that dopamine is involved and plays an important role in motivation and reward,” he said. “There is a whole spectrum of how you segment various depressed states. More atypical depressions could respond well [to TRIs], because the belief is that dopamine could be more involved” in these depressions, he said.

Still, it’s way too early to get too excited about these drugs. Lots of drugs seem promising in early development, only to wash out for unpredictable reasons in late stage testing.

The partners did not disclose financial terms of the deal. In a statement, AstraZeneca said it is licensing a portfolio of preclinical drugs from the institutions, and establishing a research collaboration with them to look for other compounds.

Source: The Wall Street Journal

Popularity: 5% [?]

AstraZeneca announced its submission of SEROQUEL XR (quetiapine fumarate extended release tablets) to European regulatory authorities seeking approval for both short-term and maintenance treatment of Generalised Anxiety Disorder (GAD). Building on the US GAD submission announced in May this year,1 this is the first time approval has been sought in Europe for an atypical antipsychotic medicine for the treatment of GAD. Read the full story

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Wyeth Pharmaceuticals, a division of Wyeth (NYSE: WYE), today provided an update on its global strategy for desvenlafaxine for the treatment of major depressive disorder (MDD) in adults.

Desvenlafaxine has already been approved for the treatment of MDD in adults in the United States, Australia and Brazil, and applications are currently pending in 22 markets. As part of its global regulatory strategy, and in consultation with the Committee for Medicinal Products for Human Use of the European Medicines Agency, the Company has chosen not to pursue its central European Marketing Authorisation Application at this time. Wyeth remains committed to making desvenlafaxine available to patients with MDD around the world, including in Europe. It is available in the United States under the name PRISTIQ.

“We are considering a number of options to support depressed patients and their families,” says Gary L. Stiles, M.D., Executive Vice President and Chief Medical Officer. “There are millions of patients with depression, and clearly more treatments are necessary.”

Wyeth has a long history of innovation in neuroscience. In 1993, the Company introduced the first serotonin-norepinephrine reuptake inhibitor, which has been prescribed to millions of people worldwide. Building on this research platform, desvenlafaxine represents Wyeth’s newest antidepressant therapy.

About Wyeth Pharmaceuticals

Wyeth is one of the world’s largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing and marketing of pharmaceuticals, vaccines, biotechnology products and non-prescription medicines that improve the quality of life for people worldwide. The Company’s major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort Dodge Animal Health.

The statements in this press release that are not historical facts are forward-looking statements that are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties include, without limitation, the inherent uncertainty of the timing and success of, and expense associated with, research, development, regulatory approval and commercialization of our products and pipeline products (including future regulatory action regarding our pending applications in other countries for desvenlafaxine for the treatment of major depressive disorder and the treatment of vasomotor symptoms, as to which no assurance can be given); government cost-containment initiatives; restrictions on third-party payments for our products; substantial competition in our industry, including from branded and generic products; emerging data on our products and pipeline products; the importance of strong performance from our principal products and our anticipated new product introductions; the highly regulated nature of our business; product liability, intellectual property and other litigation risks and environmental liabilities; uncertainty regarding our intellectual property rights and those of others; difficulties associated with, and regulatory compliance with respect to, manufacturing of our products; risks associated with our strategic relationships; economic conditions including interest and currency exchange rate fluctuations; changes in generally accepted accounting principles; trade buying patterns; the impact of legislation and regulatory compliance; risks and uncertainties associated with global operations and sales; and other risks and uncertainties, including those detailed from time to time in our periodic reports filed with the Securities and Exchange Commission, including our current reports on Form 8-K, quarterly reports on Form 10-Q and annual report on Form 10-K, particularly the discussion under the caption “Item 1A, RISK FACTORS” in our Annual Report on Form 10-K for the year ended December 31, 2007, which was filed with the Securities and Exchange Commission on February 29, 2008. The forward-looking statements in this press release are qualified by these risk factors. We assume no obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

Source: Wyeth Pharmaceuticals

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Research findings suggest that selective serotonin-reuptake inhibitors (SSRIs) may reduce fertility in men.
In the five-week study, sperm samples of 35 healthy men were analysed before the patients received paroxetine, marketed by GlaxoSmithKline as Paxil, and after four weeks into treatment with the therapy. Researchers found that at both time points, samples of the men’s sperm appeared normal, but DNA fragmentation tests showed that on average the proportion of sperm cells with damaged DNA increased from 13.8 percent before taking paroxetine to 30.3 percent after four weeks on the drug. Read the full story

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