Food for Thought: Key to Stopping Alzheimer’s Disease

In Germany, newpapers are widely reporting about a recent paper by a team of researchers led by  Thomas Bayer from Ernst-August University Goettingen, Germany, in which the team reports about an approach able to halt the progress of Alzheimer’s disease in mice.

For a long time, researchers have tried to stop Alzheimer’s disease (AD) by either dissolving the plaques found in the brains of AD patients or by trying to get rid of the so-called Abeta peptide that is believed to aggregate to plaques. However, none of these approaches has been successful so far.

A couple of years ago, researchers from the biotech company Probiodrug AG (Halle, Germany) found that the major culprit for the detrimental aggregation of peptides to plaques is not Abeta as such, but a variation carrying a pyroglutamate residue. This pyroglutamated Abeta peptide (pGlu-Abeta), they found, is generated by a hitherto unknown reaction catalyzed by the brain enzyme glutaminyl cyclase (QC). pGlu-formation leads to stabilization of the peptide and protection against cleavage. Moreover, Probiodrug has been able to demonstrate that pGlu-Abeta peptides show increased neurotoxicity, a prolonged half-life and an increased tendency for aggregation. They also form the seeds of the typical plaques observed in the brain of AD patients.

While Probiodrug is developing small molecule inhibitors of the QC enzyme to halt the disease, Thomas Bayer (who is a member of Probiodrug’s Scientific Advisory Board) and his team generated a monoclonal antibody against pGlu-Abeta. Passive immunization of transgenic mice models of AD  with this monoclonal antibody significantly reduced overall Abeta plaque load and levels of pGlu-Abeta, and also normalized behavioral deficit in the mice.

Later this month during the Neuroscience 2010 conference, Probiodrug will demonstrate that increasing pGlu-Abeta potentiates the behavioral deficits observed with transgenic AD mouse models significantly, and will also presented data showing that inhibitors of QC can reduce the level of pyroglutamated beta-amyloid species and alleviate the observed behavioral changes.

While the approach presented by Thomas Bayer will take a few years to reach the clinic, Probiodrug’s first small molecule QC inhibitor already has reached the regulatory phase.

Company News: biocrea acquires CNS pipeline and PDE inhibitor platform from Biotie

In a management-buyout, biocrea GmbH is taking over  the CNS pipeline and phosphodiesterase enzyme (PDE) inhibitor platform from Finnish Biotie Therapies Corp.

The company currently has a pipeline of three PDE inhibitors at research and preclinical stages, which will be advanced into clinical development by 2012. The compounds have already demonstrated efficacy in preclinical animal models for schizophrenia, memory impairment, depression and anxiety.

biocrea is based in Radebeul near Dresden, Germany, and will be led by Dr. Tom Kronbach, former CSO of Biotie.

More details can be found soon at biocrea’s website.

Food for Thought: Posing Stem Cell Therapy at Risk

Many researchers agree that stem cells – whether they originate from embryos or from adults – bear great therapeutic potential. They are toti- or pluripotent cells, which by definition are able to regenerate all sorts of damaged tissue – provided their differentiation is confined to the desired environment, leads to the right type of tissue and can be controlled so as not to give rise to side effects, e.g. tumors.

How to fulfill these preconditions is under thorough investigation in many research institutions, but most experts agree that science is not there yet.

Nevertheless, some researchers have set out to try – and the danger is great that stem cell therapy therefore will follow the thorny gene therapy road that started in the early nineties with unfounded experiments, serious side effects, and deaths of patients.

The first stem cell therapy related death is already there: as reported by German magazine “Wirtschaftswoche” today, this month an eight years old boy died from cerebral hemorrhage after receiving an injection of autologous stem cells into his brain. He had been treated by researchers from German stem cell therapy company XCell-Center (Düsseldorf, Germany). In Germany, autologous stem cell therapies are regarded as individual medicinal products (“Individualarzneimittel”), which require a manufacturing authorization but no regulatory approval as a drug. Already in spring, a ten years old boy developed the same condition after stem cell treatment of his brain by XCell-Center. Luckily, he survived.

But the FDA-approved clinical trial involving embryonic stem cells that started in Atlanta, GA, last week is also met with scepticism by experts. In this trial, the first patient  suffering from spinal cord injury was injected with about 2 million oligodendrocyte progenitor cells derived from human embryonic stem cells. While the researchers of Atlanta’s Shepherd Center and stem cell company Geron Corp., sponsor of the trial,  hope that the cells will form a restorative coating around the damaged spinal cord, experts such as Volker Dietz, professor at Neuroscience Center Zurich and a specialist in treating paraplegic patients, react with “disgust and infuriation”. He told German Sunday paper “Frankfurter Allgemeine Sonntagszeitung” this weekend that the treatment approach was unfounded as the regeneration of nerve cells is far from being understood and previous experiments transplanting coating cells – the cells the US researchers are trying to generate – did not lead to any effects. Dietz said, among his fellow experts, he had “not heard a single positive voice yet”.

After two decades, gene therapy today is a niche application with sparse successes, which is the result of serious blows the field experienced after some of the first patients died from side effects such as leukemias. Consequently, parliaments, regulators, funding agencies and the public as well as investors regarded the field as dangerous and too risky to pursue. With trials not supported by many specialists and the first dead patient, it seems the same scenario is unfolding today. Therefore, today’s  self-styled pioneers of stem cell therapy  not only pose patients at risk, but the field as a whole.

Company News: Micromet Announces IND for MT111 Trial Obtained by Partner MedImmune

Micromet, Inc. (NASDAQ: MITI) today announced that MedImmune, licensee for Micromet’s MT111, plans to initiate a Phase 1 trial in patients with advanced gastrointestinal cancers based on an investigational new drug (IND) application recently accepted by the U.S. Food and Drug Administration (FDA).

MT111, also known as MEDI-565, is a BiTE® antibody designed to direct a patient’s T cells, the body’s most potent killer cells, against cancer cells that express carcinoembryonic antigen (CEA). CEA is a protein found on the surface of a number of gastrointestinal cancers, including colorectal, esophageal and gastric cancers.

MT111 will be Micromet’s third BiTE antibody to progress to clinical trials. Moreover, MedImmune’s decision demonstrates its ongoing confidence in the BiTE principle. Last year, MedImmune had decided to hand back to Micromet all rights to blinatumomab, a BiTE molecule in development for blood cancers.
Blinatumomab last months entered a pivotal trial in adult patients with MRD-positive acute lymphoblastic leukemia (ALL) and a Phase II trial in adult patients with relapsed/refractory ALL.

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