Deep brain stimulation is a promising therapy for epilepsy, US researchers from Stanford University have said.

In a clinical trial, 110 people had electrodes implanted in their brains and their seizures were monitored.

Forty-one per cent of patients showed a reduction in seizures after 13 months while 56% experienced a reduction after two years.

The patients all suffered from regular epileptic seizures and had failed to respond to drug treatment.

Deep brain stimulation (DBS) is a surgical treatment involving the implantation of a medical device called a brain pacemaker, which sends electrical impulses to specific parts of the brain.

In the group of patients who received brain stimulation, researchers noted a 41% reduction in seizures compared to a 14.5% decline in seizures in a control group. This group did not receive stimulation.

Invasive therapy

Epilepsy is a common neurological disorder which is characterised by recurrent seizures. These seizures can cause temporary loss of consciousness, convulsions, confusion or disturbances in sensations.

According to the World Health Organization, epilepsy affects 50 million people worldwide.

Previous studies indicate that one third of those with epilepsy do not respond to anti-epileptic drugs.

Dr Robert Fisher, director of the Epilepsy Centre at Stanford University and lead author of the study, said electrical deep brain stimulation does reduce seizure frequency in patients.

But he cautioned: “DBS therapy is invasive and serious complications can occur. Additional clinical knowledge would help to determine the best candidates for DBS therapy.”

Simon Wigglesworth, deputy chief executive at UK charity Epilepsy Action, said: “We have been hopeful for some time that deep brain stimulation may be a treatment option for some people with epilepsy.

“This study is exciting news and could be an important development in the treatment of epilepsy in the 30% of people whose seizures don’t respond to traditional drug therapies.”

The research is published online in the journal Epilepsia.

Source: BBC NEWS

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Substantial progress has been made over the last 15 years in the healthcare community’s ability to diagnose and treat epilepsy and its complications. Yet this progress in epilepsy management has not reached most of the 50 million people around the world, including many of the nearly three million people in the United States who have the disorder.

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According to Steven C. Schachter, M.D., president of the American Epilepsy Society (AES), there is an enormous gap between what is currently being done and what is possible today to lessen the burden of epilepsy around the world. The consequences are not insignificant, as uncontrolled epilepsy leads to a diminished quality of life, and a greater risk of disability and death.

Patrick Kwan, MD, PhD, of the Chinese University of Hong Kong, and Eric R. Hargis, president and CEO of the Epilepsy Foundation, joined Dr. Schachter to address the treatment gap in epilepsy at the AES 63rd Annual Meeting held here at the Hynes Convention Center. Dr. Kwan participated in an international committee of epilepsy experts that has developed the first ever global, consensus definition of refractory epilepsy. The newly developed definition will be presented during a special symposium on Tuesday. (ILAE Symposium: Redefining Treatment Resistant Epilepsy)

Citing data from the World Health Organization (WHO), Dr. Schachter says, “An astonishing three-quarters of the global population with epilepsy get no treatment whatsoever for their seizures. While most patients here in the U.S. receive some form of therapy, there are racial, ethnic, and socioeconomic disparities in access to treatment, surgery in particular, and significant under-diagnosis and treatment of associated complications of mood, memory and cognition.” (Platforms B.03)

In a study scheduled for presentation on Sunday, for example, researchers at a specialized epilepsy center will report on eighty-three pediatric epilepsy patients referred to the center for pre-surgical evaluation. Some of these patients had been previously evaluated but remained untreated for complications secondary to their epilepsy. (Abstract 2.169)

Researchers in another study to be reported here have found there continues to be a major gap averaging seventeen years between the diagnosis of epilepsy and pre-surgical evaluation at a specialized epilepsy center in the U.S.. Professional guidelines recommend that patients be evaluated as potential surgery candidates after failing appropriate trials of first-line antiepileptic drugs, trials typically taking less than two years. The research team says reasons for the wide gap in time to treatment need to be studied. (Abstract 1.114 and Platform C.09)

“Even with the plethora of epilepsy therapies now available,” Dr. Schachter says, “the CDC estimates that at least 45 percent of people with epilepsy here in the U.S. continue to experience seizures. Complete freedom from seizures is not a possibility for everyone who has epilepsy. But it is important for patients with continuing seizures and their healthcare providers to make every effort toward that goal.”

Seizures are not benign. Mounting evidence suggests that they can lead directly to brain injury, permanent disability and death. Animal research suggests the injury may be due to seizures affecting the structure and function of dendrites, neuronal branches that connect brain cells. (Abstracts 3.028 and 3.136) Leading epilepsy experts recommend early aggressive treatment to prevent these possible severe consequences.

Dr. Kwan notes that this recommendation is followed less often in practice than actually observed. The care that is provided is further complicated by a variety of standards for defining refractory epilepsy which can also contribute to the sub-optimal care that some epilepsy patients are getting.

“The new consensus definition represents, for the first time, a common language in recognizing refractory epilepsy that can be applied by clinicians at all healthcare levels,” Kwan says. “We believe its general adoption into clinical practice can have a significant impact in improving patient care by providing clinicians a framework to recognize and refer patients fulfilling the definition to specialist centers promptly for further assessment and management. Perhaps equally important, it will improve the interpretation of research results, which, in itself, can help in raising the level of epilepsy care.”

The new definition is but one of many measures focused on the healthcare community that is needed to assure patients get state-of-the-art care. Beyond this there is much that people with epilepsy themselves can do to improve the care they receive, according to Mr. Hargis. “Many patients feel that what they experience from epilepsy and its treatment is ‘as-good-as-it-gets’. A perception they may get from healthcare providers. Programs are needed to inform patients that there are solutions to their feelings of depression and the treatment of side effects they experience. And, one of the keys is better communication with their doctors.”

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A number of recent studies, including research supported by the Epilepsy Foundation, have found that mood disorders and drug toxicity affect quality of life of patients, more than the frequency or severity of their seizures. “Educational programs are needed that encourage healthcare providers to question patents and to offer appropriate remedial options for reducing co-morbidities and the impact of the disorder itself,” Hargis says.

The heavy toll that undiagnosed, untreated and sub-optimally treated epilepsy imposes on the millions of people with epilepsy in the U.S. and around the globe has led the World Health Organization to raise the international campaign against the disorder to the highest level within its organization. Closing the wide gap in treatment will require major efforts on the part of governments, healthcare communities, researchers, and affected individuals and families everywhere. But, with people’s lives at stake, the epilepsy representatives say, there is no other course.

Source: American Epilepsy Society

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UCB and Biogen Idec have discontinued a mid-stage trial of an investigational multiple sclerosis treatment which demonstrated “no clinically relevant benefit for patients”.

The companies said that a preliminary interim analysis of a Phase II study of CDP323 for the treatment of relapsing MS showed that patients enrolled in this clinical trial did not benefit as much as expected compared to placebo after a six-month treatment period. CDP323 is an orally-active small-molecule alpha-4 integrin inhibitor and UCB said that the results of this interim analysis will “trigger a re-valuation” of the compound. The Belgian firm added that it will take a “high double-digit million pre-tax euro” charge.

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As for Biogen, the company noted that no cases of the potentially fatal brain infection progressive multifocal leukoencephalopathy were noted. This is a relief given that just a day earlier, it was disclosed that the company’s flagship MS drug Tysabri (natalizumab), which is partnered with Ireland’s Elan Corp, has been linked to a 10th case of PML.

Neupro back on EU market
Better news for UCB came with the confirmation that the European Commission has lifted restrictions on its Parkinson’s disease drug Neupro (rotigotine), the Brussels-based firm’s transdermal patch for Parkinson’s disease.

A year ago supplies of the drug were limited to patients already on the medicine due to the discovery of crystallisation problems with the product. Those problems have been sorted out and a month ago, European Medicines Agency’s Committee for Medicinal Products for Human Use recommended a lifting of the restrictions. Neupro has also been cleared for use for the first time as a treatment for adults with restless leg syndrome.

Positive lacosamide data
Even more good news for UCB came with the release of pooled data presented at the International Epilepsy Congress in Budapest, which showed that the firm’s antiepileptic Vimpat (lacosamide) significantly improved seizure control, increased seizure freedom rates during the maintenance phase and enhanced quality of life and patient function, when used as adjunctive therapy.

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Elinor Ben-Menachem of Gothenburg University, noted that some 60% of people living with epilepsy have partial-onset seizures and around one-third remain uncontrolled, despite trying treatment with a range of drugs. These latest studies support the effectiveness of lacosamide in helping these patients, she added.

Source: PharmaTimes

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Anavex Life Sciences Corp. (“ANAVEX”) (OTCBB: AVXL) today announced the immediate appointment of Herve de Kergrohen, MD, MBA, as its Chief Executive Officer (CEO) and director. Dr. de Kergrohen is an accomplished senior executive who has successfully founded and developed numerous life sciences companies throughout his career.

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With more than 25 years in senior and executive management positions, Dr. de Kergrohen has extensive experience in building and transforming organizations. He played a key role in building the life sciences portfolio with CDC Innovation, an international venture capital firm with over 415-million Euros under its management.

“I am excited to join ANAVEX as the company prepares to enter Phase 1 clinical trials with ANAVEX 2-73, its lead compound for the treatment of Alzheimer’s disease,” said Dr. de Kergrohen. “With promising results from pre-clinical studies, ANAVEX 2-73, a sigma ligand, shows potential to alter the course of Alzheimer’s disease through novel synergies of sigma and other receptors involved in neuroprotection, mnesic mechanisms and apoptosis. This new approach, backed by leading scientists, has given ANAVEX a large pipeline through its productive drug discovery platform, not only in CNS, but also in cancer therapy. I look forward to steering the company through its next phase of growth.”

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Dr. de Kergrohen has held CEO, chairman or director roles with more than 12 companies in the United States Europe. During his tenure as CEO of Praxim, Dr. de Kergrohen led the company beyond R&D to become an innovative orthopedic provider and a leader in robotic-assisted surgery. and

In 2000, Dr. de Kergrohen co-founded Global Biomedical Partners, the asset management firm of International Biomedicine Holdings (“IBMH”), a $400-million fund based in Basel, Switzerland. Under his guidance IBMH became the lead investor in several emerging biotech companies in the U.S. before they became NASDAQ listed.

“ANAVEX is pleased and privileged to welcome an executive of Dr. de Kergrohen’s caliber to the company,” said Harvey Lalach, President of ANAVEX. “We look forward to his contributions and leadership as we work towards proving the safety and efficacy of our compounds in clinical trials and confirm the excellent results achieved to date in animal models.”

Dr. de Kergrohen’s background includes work as a fund manager with public equity funds such as DH LifeSciences, which he founded while working as the head analyst at Darier Hentsch & Cie in Geneva. He also led the worldwide healthcare team of UBS Asset Management, advising the management of $1 trillion in assets.

From 1989 to 1995, Dr. de Kergrohen worked in the U.S. pharmaceutical industry at Sandoz Pharmaceuticals and GD Searle, holding various positions in drug development and marketing.

Dr. de Kergrohen currently serves as an advisor to various public organizations such as Eclosion, a Geneva-based biotech incubator that he helped create, the Handicap Agency in Paris and the United Nations Development Program. He is the founder of BioData, a biotech conference held annually in Geneva.

Dr. de Kergrohen holds a Medical Degree from Universite Louis Pasteur in Strasbourg and a MBA from INSEAD (Fontainebleau, France). He has contributed more than 100 articles to various journals around the world.

About Anavex Life Sciences Corp.

Anavex Life Sciences Corp. (www.anavex.com) is an emerging biopharmaceutical company engaged in the discovery and development of novel drug targets for the treatment of cancer and neurological diseases such as Alzheimer’s, epilepsy and depression. The company’s proprietary SIGMACEPTOR(TM) Discovery Platform involves the rational design of drug compounds that fulfill specific criteria based on unmet market needs and new scientific advances. Selected drug candidates demonstrate high, non-exclusive affinity for sigma receptors, which are involved in the modulation of multiple cellular biochemical signaling pathways.

ANAVEX’s SIGMACEPTOR(TM)-N program involves the development of novel and original drug candidates that target neurological and neurodegenerative diseases (Alzheimer’s disease, epilepsy, depression, pain). The company’s lead drug candidates exhibit high, non-exclusive affinity for sigma receptors with strong evidence for anti-amnesic and neuroprotective properties. The company believes that oxidative stress, not amyloid-beta, is the cause of Alzheimer’s. ANAVEX 1-41 and ANAVEX 2-73 modulate sigma receptors, a unique class of receptor molecules, to guard against oxidative stress and repair cells compromised by its effects. So far, through the advanced pre-clinical phase of development, the compounds have performed extremely well in well-recognized animal models of Alzheimer’s disease, underscoring the promise of the company’s new alternative approach to the disease.

ANAVEX’s SIGMACEPTOR(TM)-C program involves the development of novel and original drug candidates targeting cancer. The company’s lead drug candidates exhibit high, non-exclusive affinity for sigma receptors with strong evidence for selective pro-apoptotic, anti-metastatic and low toxicity properties in various types of solid cancers. ANAVEX 7-1037 has already demonstrated its ability to significantly delay the growth of cancerous tumors in patient-derived xenografts during advanced pre-clinical studies.

Forward-Looking Statements

Statements in this press release that are not strictly historical in nature are forward-looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks and uncertainties inherent in drug discovery and development, which include, without limitation, the potential failure of development candidates to advance through preclinical studies or demonstrate safety and efficacy in clinical testing and the ability to file an IND or commence clinical studies. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All forward-looking statements are qualified in their entirety by this cautionary statement and Anavex Life Sciences Corp. undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereo.

Source: Anavex Life Sciences Corp.

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GlaxoSmithKline announced Monday that the FDA approved Lamictal XR (lamotrigine) as a once-daily add-on therapy for patients with epilepsy aged 13 years or older who experience partial onset seizures.

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The drugmaker said the approval was based partly on results from the randomised ARMOR study involving 236 patients aged 13 years or over who were inadequately controlled on one or two antiepileptic drugs. Data from the study showed a significant reduction in seizure frequency over the 19-week treatment period, with Lamictal XR reducing partial seizures by 47 percent in patients taking the drug, compared to a reduction of 25 percent in patients who received placebo, GlaxoSmithKline said.

The company indicated that the extended-release formulation of Lamictal will be available in the US this summer.

Source: FirstWord

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The research discovery builds on previous work identifying a specific molecular target whose increased activity is associated with seizure disorders, a potassium channel known as the BK channel. Read the full story

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Scientists report that an epilepsy susceptibility gene can get switched on in mice that have not inherited the active form of the gene, which subsequently increases the tendency to have seizures. This finding helps explain how some people without a genetic predisposition to epilepsy can develop the disorder, according to the team from Wake Forest University School of Medicine.

The gene codes a calcium channel in the brain that underlies seizures, according to the study called “An Acquired Channelopathy Involving Thalamic T-Type Ca^2+ Channels after Status Epilepticus” appearing this month in the Journal of Neuroscience.

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Some epilepsies are linked to inherited traits, but many appear to arise through acquired alterations in neuronal excitability. Status epilepticus (SE) is associated with numerous changes that promote spontaneous recurrent seizures (SRS). Studies have suggested that hippocampal T-type Ca^2+ channels underlie increased bursts of activity integral to the generation of these seizures.

The thalamus also contributes to epileptogenesis, but no studies have directly assessed channel alterations in the thalamus during SE or subsequent periods of SRS, according to the Wake Forest group. They thus decided to investigate longitudinal changes in thalamic T-type channels in a mouse model of epilepsy. They measured changes at different time intervals as the mice developed epilepsy.

The researchers found that after an initial seizure, a particular type of calcium channel begins to be expressed where it wasn’t before. They observed that the particular gene that codes for the misplaced channel was upregulated during the SRS period. They verified the functional involvement of this gene by using inhibitors, which reduced the activity of the calcium channels in the thalamus.

“Certain kinds of channels are normal and expected in the thalamus, but after an initial seizure, more copies of a channel that aren’t normally found in this brain region begin to appear,” explains graduate student John Graef, the first author on the study. “The brain activity then becomes dominated by the new copies of this channel. It helps explain how seizures can develop and spread.”

The scientists thus conclude that SE produces an acquired calcium channel network by inducing long-term alterations in thalamic T-type channels. This contributes to characteristic changes in excitability observed during SRS.

Source: GEN News

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An international team of scientists have found out why Alzheimer’s disease sufferers go on to develop epilepsy.

Led by scientists at Aberdeen University in Scotland, the research team have discovered that a protein in the brain accumulates in clumps in the brains of people suffering from dementia.

The clumps of proteins make the nerve cells too sensitive, which in turn lose their ability to communicate coherently with other nerve cells.

The researchers say that this makes Alzheimer’s patients more susceptible to seizures, reports the Scotsman.

While official figures show that nearly one third of Alzheimer’s patients suffer from some degree of epilepsy, this is for the time that a link has been established between the two conditions.

Professor Tibor Harkany, the Aberdeen neurobiologist who led the research, said that the findings could lead to changes in the drugs used to treat Alzheimer’s disease.

He said that the research team had discovered that the “beta-amyloid protein”, a key component of the plaques that clog the brain of an Alzheimer’s patient, was causing cells to short-circuit and fire too many electrical signals.

Source: Silver Scorpio- International News

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• Eisai Set to Become an Emerging Leader in the Treatment of Epilepsy

Eisai Europe Ltd (London; Chairman & CEO Yutaka Tsuchiya), the European subsidiary of Eisai Co., Ltd. , and Bial-Portela & CA, S.A., (S. Mamede do Coronado, Portugal, CEO Dr Luis Portela) today announced the signing of a licence and co-promotion agreement in which Eisai receives a sole license to market, promote and distribute the novel once daily anti-epileptic Zebinix(R) (eslicarbazepine acetate), within Europe(1).

Under the terms of the agreement, Bial will receive EUR95million consisting of an upfront payment plus milestone payments for further epilepsy approvals within Europe. Bial will maintain ongoing development and production rights and the option to co-promote with Eisai throughout Europe and will supply finished product to Eisai.

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Zebinix(R), subject to approval by the European Medicines Agency (EMEA), will initially be indicated for the adjunctive treatment of partial-onset seizures, with or without secondary generalisation, in patients 18 years and older with epilepsy. Zebinix(R) was submitted to the EMEA by Bial in March 2008 and approval is anticipated in Q2 2009.

The safety and efficacy of Zebinix(R) has been shown in three phase III double-blind, randomised placebo-controlled trials in 1,049 patients with partial onset seizures. Additionally, these subjects were followed up long term in an open label extension. In these studies, Zebinix(R) demonstrated significant sustained improvements in seizure frequency, reduced depressive symptoms, and significantly improved scores in health related quality of life.

“It is as important to consider the implications on the quality of a patient’s day-to-day life, as well as effective seizure control, when making the therapeutic evaluation of a new anti epileptic agent,” said Professor E. Ben-Menachem, University of Gothenburg, Sweden. “In addition to sustained reductions in seizure frequency, Zebinix(R) also demonstrated a significant improvement in patient quality of life and reduction in depressive symptoms.”

Yutaka Tsuchiya, Chairman & CEO of Eisai Europe said “We are delighted to be working with Bial to bring to patients such a potentially promising new treatment for epilepsy. Zebinix(R) joins our existing successful portfolio of anti-epileptics, which includes Zonegran(R) (zonisamide) and Inovelon(R) (rufinamide). This helps us to fulfil our Corporate mission of ‘human health care’ (hhc), to provide innovative, high quality medicines to meet the ever changing unmet medical needs of the health care profession as well as patients and their families.”

Commenting on the deal, CEO of Bial, Dr Luis Portela, said “this partnership with Eisai is a landmark event for Bial in Europe. Zebinix(R) represents the first results of our R & D efforts in the CNS area. It is the result of many years of hard work and dedication and we believe Eisai is the right partner for Bial in Europe, an emerging leader in the field of epilepsy with the know-how and experience to make Zebinix(R) a leading choice for patients suffering with Epilepsy.”

Source: BioSpace

Popularity: 3% [?]

“Anavex believes that oxidative stress, not amyloid-beta, is the cause of Alzheimer’s; seeking partners for early-stage compound, executives say”

Anavex Life Sciences (OTCBB: AVXL) believes that oxidative stress, not amyloid-beta, is the cause of Alzheimer’s disease, and is currently seeking partners to develop an early-stage compound, according to Harvey Lalach, co-founder, president, chief financial officer and director.

Lead candidate ANAVEX 1-41 has a synergistic neuroprotective and anti-apoptotic effect in animal models that use amyloid (beta) 25-35 peptide to simulate the condition, according to results presented at the 2008 International Conference on Alzheimer’s Disease.

“If something comes across the table, we’ll address it,” Lalach said about potential partnerships. “The game plan would be to move one compound through Phase I in CNS. And if something comes to the table prior to that, we would seriously look at that.”

There has been “significant interest” from big pharma in both the company and its compounds, he noted, adding that there is a need for capital moving forward, as R&D to develop an Alzheimer’s candidate is very costly. “With additional capital, we can move other compounds into Phase I. We also have oncology compounds at various stages of development,” he said.

Companies developing late-stage candidates in Alzheimer’s include Eli Lilly (NYSE:LLY), Wyeth (NYSE:WYE), Pfizer (NYSE:PFE), GlaxoSmithKline (NYSE:GSK) and Bristol-Myers Squibb (NYSE:BMY). Avanex became publicly listed through a reverse takeover at the beginning of 2007, Lalach noted. The company was funded privately with approximately USD 15m in research capital. “It got to the point where the results were encouraging, and investors wanted to move this compound forward as soon as possible,” he said.

The company’s SIGMACEPTOR-N program involves the discovery and development of drug candidates targeting neurological and neurodegenerative diseases, such as Alzheimer’s, epilepsy and depression.

Sigma-1 receptors have been cloned and shown to be distinct from any known receptor class. In the central nervous system, they have been shown to be involved in the modulation of neurotransmitter receptor function, neurotransmitter release and response, as well as memory and learning processes, demonstrating potential neuroprotective and anti-amnesic properties.

“The lead compound comes from the sigma receptor platform, which is a proprietary platform technology that generates molecules based on sigma ligands and receptors,” Lalach said. There is interest from large pharma, as the platform has a potential to create multiple compounds across a variety of different disease indications, he said. George Kalkanis, Anavex’s co-founder and vice-president for strategic planning, said to the surprise of the Alzheimer’s community, it turns out that the current market leader, Pfizer’s Aricept, also affects sigma ligand. Pre-clinical experiments in mice showed that Anavex’s drug can attain all these synergistic receptors, he noted.

“We don’t care if the neuronal toxicities are coming from amyloid or not,” he said. “It turns out that diluting or reducing amyloid beta protein is not a means of treating Alzheimer’s disease.”

The failure of Neurochem and Myriad Genetics’ Alzheimer’s candidates – which worked to reduce or prevent amyloid build-up – is proof of the fact that targeting the amyloid pathway may be wrong, said Kalkanis. Alzheimer’s is due to oxidative stress, and amyloid beta may be a result of oxidative stress, he noted. The oxidative stress pathway may also activate other undesirable effects. The amyloid plaques can come initially as a defense, which is why they accumulate in the brain, he said.

Anavex plans to conduct a single dose-ascending study, which will include 40 volunteers in Europe. A multiple ascending dose study will include 24 volunteers, according to Kalkanis. “These studies will be able to establish the profile of the drug.”

The company is open to any prospects, said Lalach. “Our strategic initiative is to raise some money from investors and advance our first compound to the end of Phase I and beginning of Phase II trials,” he added. “We don’t exclude any proposals for partnership.”

The company recently appointed Dr Mark Smith – a leading researcher who is executive director of the American Aging Association and editor-in-chief of the Journal of Alzheimer’s Disease – to its scientific advisory board. “We’re in the process of upscaling synthesis of the compound, and selecting the right contract research organization,” Lalach said. Anavex has a market cap of USD 50m.

Source: Pharmawire

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