“Our technology potentially addresses several major safety concerns for developing a vaccine to beta-amyloid, a protein which is naturally present in the brain and other tissues,” says Mindset CEO Dr. Daniel Chain.An Israeli company called Mindset BioPharmaceuticals has become the …
CEO Daniel Chain, in making the announcement at the Society of Neuroscience Meeting in New Orleans, pointed out that preliminary studies carried out by the company indicate that the Mindset vaccine may not cause the side effects that led Elan Corp. and Wyeth-Ayerst Laboratories to stop an advanced stage clinical trial for their Alzheimer`s vaccine in March 2002.
Alzheimer’s disease continues to be a major unmet medical need, a neurodegenerative disorder affecting approximately 8 million Europeans and Americans, with the number expected to rise dramatically with an increasing elderly population.
As no cure or disease-modifying therapy has been developed for Alzheimer`s disease, the Elan-Wyeth-Ayerst vaccine trial was greeted with much anticipation. But when patients began to show signs of neuro-inflammation the trial was halted.
Despite the disappointment of the vaccine being found to cause adverse side effects, post-trial analysis of the data has shown that the vaccine was quite efficacious. “A recent paper in a leading journal, Neuron, describes the lack of cognitive decline after one year in 20 patients receiving the Elan vaccine,” notes Cheryl Fitzer-Attas, Mindset`s Vice President for Research & Development. “This underscores the clinical promise for this type of treatment strategy.”
“We believe this to be the first patent ever issued that specifically is directed to a peptide for use as a vaccine and immunizing composition against the Alzheimer’s toxin, beta-amyloid,” Chain told ISRAEL21c. “An earlier patent that was issued in the early 90s describes a homeopathic treatment in which patients are treated with the natural toxin without additional modulators (adjuvants) to stimulate an immune response. Mindset’s unique patented technology is used with an adjuvant and therefore represents the first classical vaccine for Alzheimer’s disease. Moreover, Mindset’s technology is based on synthetic and chemically modified homologs of beta-amyloid. In contrast to the natural form, the homologs are not toxic to nerve cells.”
Mindset`s vaccine, invented by scientists at New York University School of Medicine, and licensed to Mindset for development, elicits a response against the beta-amyloid protein known to be toxic to nerve cells and to form insoluble aggregates that accumulate in the brains of Alzheimer`s patients. This unique vaccine approach is based on soluble, synthetic homologues of the human amyloid toxin, which were found to be highly immunogenic when tested in animals. Also, in relevant animal models of Alzheimer`s disease, the Mindset vaccine was shown to inhibit the deposition of toxic amyloid fibrils and to improve cognition.
“Mindset`s technology potentially addresses several major safety concerns for developing a vaccine to beta-amyloid, a protein which is naturally present in the brain and other tissues,” said Chain. “These concerns include neurotoxicity of the native protein and difficulties in inducing an antibody response in elderly patients.”
With regard to another major safety concern – the potential of Alzheimer’s vaccines to induce an adverse autoimmune response – Mindset also offers good news. “In a related discovery, we have found out how to anticipate and also reduce the possibility for this undesirable reaction,” said Fitzer-Attas.
The vaccine is still in the preclinical stage and is unlikely to enter clinical trials before 2006, according to Chain.
“The vaccine will be first tried in healthy elderly volunteers in Phase I trials before it can be tested in Alzheimer’s patients (Phase II),” he said. “The Phase I trials would be expected to take about a year to complete before Phase II can start. We can safely assume at least seven or eight years before the vaccine could be approved by the FDA for general treatment. Given, the failure of a previous Alzheimer’s vaccine trial that was sponsored by Wyeth and Elan Pharmaceuticals and terminated prematurely because of safety issues, the challenge will be to demonstrate safety. We believe Mindset’s approach is potentially much safer but it will be necessary to carry out extensive safety testing in animals and then healthy humans before proceeding to patients.”
The development of the Alzheimer`s vaccine is only one of several different therapeutics Mindset is developing aimed at modifying the course of the disease, whereas existing therapies are essentially symptomatic, without affecting disease progression.
OXIGON, Mindset`s lead compound for Alzheimer`s disease, was one of only several drugs selected for funding out of over many late stage pre-clinical projects by the Alzheimer`s Disease Cooperative Study (ADCS), a consortium of clinical investigators and academics chartered by the U.S. National Institute on Aging.
Studies have shown that OXIGON is the most powerful known antioxidant, being 10,000 times more potent than vitamin E. The molecule has a dual mode of action: it inhibits the oxidative stress aggravating the cell death associated with AD; in addition, OXIGON is a potent inhibitor of beta amyloid fibril formation, one of the more severe manifestations of AD.
In addition, Mindset has developed a unique platform for lead drug candidate selection and optimization using transgenic mouse models to study drug effects in Alzheimer`s disease and other neurodegenerative disorders including cognitive impairment. MindGenix is a subsidiary of Mindset based in Albany, NY, which offers contract research in the transgenic models.