1) Aixlie Pharmaceuticals today ( 18 Jan 2001) announced that they have obtained the rights to develop a technology designed by researchers at the Ohio State University. It is a peptide that appears to regulate an important step in the body's autoimmune response. Recent pre-clinical research at Ohio State has indicated that this peptide has the ability to stop the autoimmune destruction of the myelin sheath in an accepted animal model for multiple sclerosis. Researchers have shown the peptide is able not only to prevent the onset of myelin destruction, but also to decrease the process once it has started. "The first Phase I study for the product is being planned currently," stated Dr. Gary Pekoe, Aixlie CEO. "We are impressed by the potential of this technology to impact not only autoimmune neurological diseases like multiple sclerosis, but foresee its testing in organ transplant, diabetes, arthritis, and any number of other conditions involving an autoimmune component."

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2) Mayo Clinic Rochester News Monday, June 5, 2000 Mayo Clinic Scientists Discover Way to Enhance Immune System that Repairs Nervous System in Mouse Model ROCHESTER, MINN. -- In a major scientific discovery, Mayo Clinic scientists conducting research in mice with central nervous system damage have found a way to enhance the immune system that resulted in nervous system repair in the mice. The study detailing the findings will be published in the Tuesday, June 6 edition of Proceedings of the National Academy of Sciences. In their study, Mayo Clinic scientists identified two natural human antibodies that, when given to mice with a chronic, demyelinating disease, caused the regrowth and repair of the myelin sheath. Myelin surrounds nerve fibers and acts as "insulation," allowing them to function properly. Previously, it was thought that damage to myelin was permanent and repair to the nervous system was not possible. In humans, damage to the myelin sheath can be caused by traumatic injury or by diseases such as multiple sclerosis, transverse myelitis and other demyelinating or genetic conditions. "Clearly, our study shows that the two natural human antibodies, when introduced into mice that had nervous system damage, safely caused substantial repair to the myelin and the nervous system," says Moses Rodriguez, M.D., a Mayo Clinic neurologist and the principal author of the study. "This is a significant step forward in our understanding of the nervous system and the immune system. Whereas we know that the immune system can have a protective effect on the body, we now are beginning to discover that the immune system may be harnessed to effect repair to the nervous system in the mouse model." In the laboratory study, mice were injected with a virus that caused demyelination in the nervous system similar to the damage multiple sclerosis causes in humans. The mice were treated with two natural human monoclonal antibodies after the onset of demyelination. This treatment promoted remyelination to an equivalent or greater extent than human intravenous immunoglobulin (IVIg), an established treatment for immune-mediated diseases. The antibodies bound to the surface of the cells that make myelin. The research also yielded the molecular sequence of the antibody which will facilitate production of the antibody in large quantities for further studies. Treatment with the human antibodies proved to be safe in mice. Currently, there is no new treatment or therapy for humans as a result of this research. It is unknown how long the development of the clinical trials will take or when the clinical trials would begin. Funding for the first stage of research was provided by the National Institutes of Health, National Multiple Sclerosis Society, Mayo Foundation and Acorda Therapeutics. Acorda Therapeutics is a biotechnology company that develops therapeutic products for spinal cord injury and other central nervous system conditions. Acorda is planning to complete the preclinical work necessary before human clinical trials can be designed. This work includes scaling up manufacturing of the antibody to produce quantities sufficient for human clinical trials, and conducting formal toxicity and pharmacokinetic studies. Ron Cohen, M.D., Acorda’s president and CEO, states, "Acorda is proud of its collaboration with Dr. Rodriguez and Mayo Clinic. The identification of this human monoclonal antibody is a significant step forward in its development as a potential therapy for people with demyelinating conditions, such as multiple sclerosis." "This type of basic scientific research is needed to advance medicine and our potential to develop new treatments and therapies for humans," says Dr. Rodriguez.

3) Promising News For All Autoimmune Diseases! Experimental Therapy May Lead to Better MS Treatment January 25, 2001 Journal of Immunology/MedscapeWire A new therapy effectively treats a disease similar to multiple sclerosis (MS) in monkeys, and the approach could soon be tested against MS and other autoimmune diseases in humans. The therapy's promising results, reported by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), will be published in the February 1 issue of the Journal of Immunology. "Current treatments for MS broadly suppress the immune system and can cause toxic side effects," says senior study author Michael Lenardo, MD, of NIAID's Laboratory of Immunology. "This treatment, called antigen-specific immunotherapy, specifically targets the immune system's T cells that cause the disease. Presumably, it would not lead to such side effects." Antigen-specific immunotherapy is based on a discovery by Dr. Lenardo and colleagues that T cells exposed to small amounts of the proteins making up the myelin sheaths are stimulated to attack the sheaths. But T cells exposed to large amounts of the same proteins will undergo a preprogrammed "self-destruct" sequence. (In fact, T cells exposed to large amounts of any antigen — a substance that provokes them to attack — will self-destruct.) Therefore, introducing large amounts of myelin proteins into the body should remove the problematic T cells and halt the disease, Dr. Lenardo explains. "The therapy is counter-intuitive; one might think it would be like pouring gasoline on a fire," Dr. Lenardo says. But the self-destruct sequence actually protects the body from having too many active T cells, which can themselves be toxic. "Like any potent weapon, you want to control how much is deployed," Dr. Lenardo explains. "The immune system doesn't let your T cells grow uncontrolled and kill you. In this case, adding more antigen smothers the fire." Dr. Lenardo and his colleagues first injected 9 male marmoset monkeys with just enough myelin proteins to stimulate their T cells to attack myelin sheaths, inducing a disease very similar to MS in humans. Three monkeys then received additional large doses of myelin proteins, 3 received moderate doses, and 3 received nothing. The monkeys were observed for 105 days. All 3 of the untreated monkeys showed clinical symptoms of the disease. In contrast, none of the monkeys in the large-dose group showed symptoms. In the moderate-dose group, 2 of the 3 showed symptoms, but those symptoms were significantly delayed. Magnetic resonance images of the animals' brains revealed severe damage to the myelin sheaths in 2 of the untreated monkeys and 1 of the moderate-dose monkeys. Minor damage did occur in the large-dose group, indicating the disease process had not been completely thwarted although it had been greatly suppressed. The treatment appeared to cause no adverse effects. Researchers at the National Institute of Neurological Disorders and Stroke assisted with the experiment. Dr. Lenardo and his colleagues are investigating how the therapy works against other autoimmune diseases in laboratory mice. One such disease under investigation is myasthenia gravis, a paralyzing condition affecting children that is caused when the immune system mistakenly attacks the receptors on muscle cells that receive nerve impulses. Autoimmune diseases such as rheumatoid arthritis, type 1 diabetes and MS affect approximately 5% of the US population. Directly and indirectly, they cost the US economy more than $100 billion per year. "Immune-mediated diseases are a major cornerstone of the NIAID research effort," says Anthony S. Fauci, MD, director of NIAID. "Efforts such as Dr. Lenardo's hold great promise for developing new treatments for individuals with autoimmune diseases." MS is a paralyzing disease that affects nerves in the brain and spinal cord, disturbing speech, vision and movement. MS primarily strikes young adults, most often women who live in northern latitudes. The disease is caused by a malfunction in the immune system: certain white blood cells called T cells mistakenly attack myelin sheaths, protective coverings that surround the signal-carrying fibers of nerve cells.

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4). 1.  Science: THC destroys brain cancer in animal research Delta-9-tetrahydrocannbinol (THC), the major active component of the cannabis plant, and a synthetic cannabinoid induced a remarkable regression of a usually fatal type of brain tumour when tested on laboratory rats, Spanish researchers said on 28 February in the journal Nature Medicine. Malignant gliomas, a quick-killing cancer for which there is currently no effective treatment, were induced in 45 rats. A third were treated with THC, and another third with the cannabinoid agonist WIN-55,212-2, while the remainder were left untreated. Within 18 days the untreated rats died. But the two cannabinoids had a dramatic effect, destroying the tumours in a third of the treated rats over a period of seven days, and prolonging the life of another third by up to six weeks. 12 days after cell injection THC or WIN-55,212-2 were continually injected directly at the site of tumour inoculation over a period of 7 days. THC administration was ineffective in 3 animals and increased the survival of 9 rats up to 19-35 days. The tumour was completely eradicated in 3 of the treated animals. Likewise the synthetic cannabinoid was ineffective in 6 rats, increased the survival of 4 rats up to 19-43 days; and completely eradicated the tumour in 5 animals. The team led by Dr Manuel Guzman from the Complutense university in Madrid said: "These results may provide the basis for a new therapeutic approach for the treatment of malignant gliomas." He said that the current experiment tested THC at very low doses and at a late stage, when untreated rats were already starting to die. He predicts that THC should work better if given earlier. But cancer treatments that work in animals may be too toxic or not effective in humans. Cannabinoids are thought to kill tumour cells by inducing programmed cell death, or apoptosis, via an intracellular signalling mechanism. Experiments carried out with two subclones of glioma cells in culture demonstrated that cannabinoids signal apoptosis by a pathway involving cannabinoid receptors, sustained accumulation of the lipid ceramide and Raf-1/ERK (extracellular signal-regulated kinase) activation, inducing a cascade of reactions that leads to cell death. In a commentary for Nature Medicine, Dr. Daniele Piomelli, from the University of California at Irvine, said the findings could have important implications. This would be the first convincing study to show that a marijuana-based drug treatment may combat cancer. If the drug works as well in humans, Piomelli says, "then this will be a paper of great importance." But it would take a lot of testing, both in animals and in people, to prove it is effective. The smoking of marihuana would not be effective. (Sources: Galve-Roperph I, Sanchez C, Cortesz ML, Gomez del Pulgar T, Izquierdo M, Guzman M: Antitumoral action of cannabinoids: involvement of sustained ceramide accumulation and ERK activation. Nature Medicine 6, 313-319 (2000); Piomelli D: Nature Medicine 6, 255-256, (2000); UPI of 28 February 2000; AP of 29 February 2000; Reuters of 29 February 2000; PA News of 29 February 2000, personel communication by Manual Guzman)   2.  Science: Cannabinoids reduce tremor in animal model of multiple sclerosis In the journal Nature scientists said on 1 March they had for the first time scientifically demonstrated the link between cannabis and the suppression of multiple sclerosis (MS) symptoms. The study with mice suffering from chronic allergic encephalomyelitis (CREAE) -- an animal model for MS -- found that cannabinoids ameliorated CREAE symptoms. The mouse MS study "is the first to show definitive objective evidence that synthetic compounds, which stimulate the receptor that cannabis (marijuana) binds to, can alleviate spasticity and tremor in an MS-like condition. This gives a rationale of why patients may perceive benefit from taking cannabis and supports the establishment of a clinical trial to assess the benefit of medical cannabis in MS," Lorna Layward, head of research of the Multiple Sclerosis Society of Great Britain and Northern Ireland, said. In the study, led by David Baker of University College in London, the researchers injected THC, other cannabinoid receptor agonists and antagonists into mice with CREAE. Layward said it was now up to drug companies to develop compounds that mimicked cannabis but avoided the side-effects experienced by cannabis smokers. The scientists cautioned the research is in the preliminary stages; whether similar results can be obtained in large-scale human studies is unknown. (Sources: UPI of 2 March 2000, Reuters of 2 March 2000; PA News of 2 March 2000)

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