CepTor Announces Patent Filing for Neurodur (C-201) Pro-Drug in Multiple Sclerosis and Other Neurodegenerative Diseases

http://tinyurl.com/aqjcb

CepTor Corporation, Inc. (OTC BB:CEPO), a development-stage biopharmaceutical company focusing on cell targeted therapeutic products for neuromuscular and neurodegenerative diseases, announced it filed a PCT international patent application for Neurodur (C-201). The application includes broad coverage of all forms of Neurodur with emphasis on compound protection for the oral pro-drug. It also speaks to multiple uses in several neurodegenerative indications including multiple sclerosis (MS). Neurodur includes the nerve tissue targeting carrier molecule, taurine, along with an analogue of the calpain inhibiting molecule, leupeptin. In the standard MS EAE mouse model, Neurodur has demonstrated significant clinical efficacy working across the blood brain barrier.

"It is hard to believe a year has already gone by since we announced our provisional filing for Neurodur," said William Pursley, Chairman and CEO of CepTor. Mr. Pursley continued, "We are very bullish about the breadth of the universe this patent allows us to draw down on as we begin prosecuting in individual countries."


About CepTor

CepTor Corporation is a development-stage biopharmaceutical company engaged in the discovery, development, and commercialization of proprietary, cell-targeted therapeutic products for the treatment of neuromuscular and neurodegenerative diseases with a focus on orphan diseases. The Company's mission is to increase the quality and quantity of life of people suffering with these diseases. An orphan disease is defined in the United States as a serious or life-threatening disease that affects less than 200,000 people and for which no definitive therapy currently exists. CepTor Corporation seeks to create an efficient orphan drug platform by taking advantage of the legislative, regulatory and commercial opportunities common to these rare diseases. CepTor's primary efforts are currently being focused on moving its lead product, MYODUR, into phase I/II clinical trials for Duchenne muscular dystrophy. The Company's broad platform technology also includes the development of products for multiple sclerosis, retinal degeneration and epilepsy.

This news release contains forward-looking statements. Such statements are valid only as of today, and we disclaim any obligation to update this information. These statements are subject to known and unknown risks and uncertainties that may cause actual future experience and results to differ materially from the statements made. These statements are based on our current beliefs and expectations as to such future outcomes. Drug discovery and development involve a high degree of risk. Factors that might cause such a material difference include, among others, uncertainties related to the ability to attract and retain partners for our technologies, the identification of lead compounds, the successful preclinical development thereof, the completion of clinical trials, the FDA review process and other government regulation, our pharmaceutical collaborator's ability to successfully develop and commercialize drug candidates, competition from other pharmaceutical companies, product pricing and third party reimbursement.

Source: Business Wire

http://www.rednova.com/news/health/256568/ceptor_announces_patent_filing_for_neurodur_c201_prodrug_in_multiple/index.html?source=r_health

http://biz.yahoo.com/prnews/050927/nytufns1.html?.v=17

<> NEW YORK, Sept. 27 /PRNewswire/ -- This past weekend, while thousands of cyclists participated stateside in MS Bike Tours®, a group of 15 U.S. military personnel concerned about the plight of those struggling with the effects of multiple sclerosis participated in a 100-mile ride in the desert terrains of Iraq. Like those living with MS, a disease whose hallmark is unpredictability, these soldiers too are living lives filled with unpredictability.

http://www.newscom.com/cgi-bin/prnh/20010328/NEW004LOGO

Photo: http://www.newscom.com/cgi-bin/prnh/20050927/NYTUFNS1

The cyclists are stationed at Forward Operating Base (FOB) Danger, in Tikrit. Major Fred Evans, 42nd Aviation Brigade Liaison Officer, organized "Team Danger," the group of cyclists. Major Evans has participated in MS Bike Tours through his local Society chapter (Greater North Jersey). He says finding riders was easy and that supporting the National Multiple Sclerosis Society is just a continuation of the values the military is based upon.

"Over here we're fighting for our country, fighting the global war on terrorism," said Evans. "With this bike tour we're trying to help people, not only in the United States, but all over the world, in fighting this disease and in trying to find a cure for multiple sclerosis."

Sergeant Doug (DJ) Saunders, stationed at FOB Gabe, where he had been planning to do a similar ride, joined Team Danger in Tikrit. Saunders first rode in the Kansas Mid America Chapter's MS Bike Tour in 2004. "Riding in the MS Bike Tour is a small show of respect and appreciation for people living with multiple sclerosis. I am committed to being a part of the cure, and I will not fail those who courageously fight this disease on a daily basis."

To date, the soldiers combined efforts have already raised at least $5,000, with more coming in. To find out more about the MS Bike Tour, Team Danger, and for additional images, visit http://www.nationalmssociety.org.

ABOUT MULTIPLE SCLEROSIS

Every hour in the United States, someone receives that frightening diagnosis: multiple sclerosis. MS is an unpredictable, often disabling disease of the central nervous system. Symptoms range from numbness and tingling to blindness and paralysis. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are giving hope to those affected by the disease. Most people with MS are diagnosed between the ages of 20 and 50, with more than twice as many women as men contracting the disease. MS affects more than 400,000 people in the U.S., and 2.5 million worldwide.

ABOUT THE NATIONAL MS SOCIETY

The mission of the National MS Society is to end the devastating effects of MS. Through its home office and 50-state network of chapters, the Society funds more MS research, offers more services to people with MS, provides more professional education, and advances more MS advocacy efforts than any other MS organization in the world. This is why we're here. For more information, call 1-800-FIGHT MS or visit nationalmssociety.org.

Padma28 and the effect on MS

http://www.ever.ch/padma28ms.htm
Experience of Padma 28 in Multiple Sclerosis

PHYTOTHERAPY RESEARCH, VOL. 6,133-136 (1992)

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Multiple Sclerosis, arachidonic acid, linoleic acid, influence of food

T. Korwin-Piotrowska, D. Nocon, A. Stankowska-Chomicz, A. Starkiewicz, J. Wojcicki and L. Samochowiec

Clinic of Neurology, Institute of Pharmacology and Toxicology, Medical Academy, Powstancow Wielkopolskich 72,

70-111 Szczecin, Poland

One hundred subjects suffering from a chronic progressive form of multiple sclerosis were randomly divided into two equal groups. Group 1 received Padma 28, two tablets three times a day, and group 2, the control, were treated only symptomatically. Treatment and observation lasted for 1 year. Examinations performed directly prior to the study and in the course of observation included- neurological state, visual and auditory evoked potentials, basic laboratory tests. A positive effect of Padma 28 was observed in 44% of patients with multiple sclerosis in the form of improvement of general condition, increase of muscle strength, decrease or disappearance of disorders affecting sphincters. In 41% of patients with initially an abnormal tracing of visual evoked potentials, an improvement or normalization was achieved. Of patients, who did not receive Padma 28 none felt better, moreover, 40% of them showed a deterioration. Tolerance of the drug was excellent Keywords: multiple sclerosis; Padma 28; treatment in 100 patients.

INTRODUCTION

Multiple sclerosis is a chronic, often progressive, demyelisation disease that is characterized by gait disturbances, visual and coordination impairment, sensory complaints and genitourinary dysfunction. Numerous studies show that abnormal immunological processes occur in this illness, in the form of humoral and cellular reactions directed to viral cerebral antigens. According to one of these hypotheses, in multiple sclerosis lymphocytes become sensitized to unidentified cerebral viral or miscellaneous antigens. Cytotoxic lymphocytes and activated macrophages are formed, and soluble factors are released (Cendrowski, 1980; Halliday and McDonald, 1977; Kuratowska et al., 1982; 1,owitzsch et al., 1976). Oligodendrocytes and myelin sheaths of the brain become the target of the cytotoxic attack in sclerosis (Cendrowski, 1986). Bach (1982) disclosed that in cerebrospinal fluid and the peripheral blood there is a decrease in suppressory lymphocytes (T,) and an increased index of helper lymphocytes (TH: T,) in the period 2 weeks prior to the attack of the disease, and up to 2 weeks after the attack.

lt is reported in the literature that Padma 28 is likely to exert an effect on immunoregulation by affecting suppressory lymphocytes (Badmajew et aL, 1982b; Brzosko et al., 1983). Considering the immunotropic properties of Padma 28 and data that the preparation may induce in humans, synthesis of endogenous interferon (Brzosko et al., 1984), we have attempted to estimate its therapeutic activity in patients suffering from multiple sclerosis. Padma 28 is an herbal mixture of the lamaistic medical science, consisting of 22 ingredients combined in a specific order, according to strict weight ratios and according to the prescription of W. N. Badmajew (Badmajew et al., 1982a). The chemical components of the preparation have been identified using gas chromatography and thin-layer chromatography (Sarnochowiec, 1983). Padma 28 stimulates the ascorbate system (Wöjcicki et al., 1989) and is able to decrease lipid peroxidation, thus exhibiting antioxidant properties (Samochowiec and Wöjcicki, 1987).

MATERIALS AND METHODS

One hundred subjects suffering from progressive (and proceeding with attacks) multiple sclerosis were randomly divided into two equal groups. Group 1, consisting of 33 women and 17 men, aged 26 to 56 years, mean 38.4 years, received Padma 28, two tablets three times a day (Table 1); Group 2, including 29 women and 21 men, aged 29 to 60 years, mean 40.1 years, was treated only symptomatically, receiving drugs to reduce pain, spasticity and cramps, and to inhibit detrusor contractions. Observation was conducted at the Medical Outpatients Clinic for Multiple Sclerosis. The study and treatment was spread over a period of 1 year for each patient.

Prior to the onset of therapy, in all patients investigations covered the general neurological state, blood morphology with a smear, blood platelets, erythrocyte sedimentation rate, biochemical studies of the blood serum (urea, creatinine, glucose, aminotransferases, alkaline phosphatase), urine analysis. Moreover, before Padma 28 was administered and directly after the end of therapy, visual and auditory evoked potentials were studied in the whole group. Visual evoked Potentials were investigated by applying the stimulation with reversal standard of chequerboard at 2 Hz frequency, by means of a monitor, repeated 200 times, successively exciting the retina of each eye. The per- formed evaluation embraced the amplitude and latency of cortical response originating from the occipital region. The established norm for cortical visual potential P, is 90-1 10 ms.

The studies of auditory evoked Potentials consisted of applying stimuli through headphones in the form of "clicks" lasting 0. 1 ms, frequency 30 Hz and intensity 60 dB, above the auditory threshold (electroneuronograph, Neuramatic 2080, Disa, Skovlunde, Denmark). These stimuli were used to excite the right and left ear, 2000 times consecutively. Then the bioelectric responses from the brainstem were estimated. Attention was paid to the individual components as responses from respective nuclei of the brainstem. The brainstem auditory evoked responses comprise a series of potentials (1-1V). Wave 1 corresponds to activation of the Vlllth nerve, waves 111111 of the cochlear and olivary nuclei, wave IV corresponds to the nuclei of the lateral lemniscus, wave V to the inferior colliculus. Latencies are often measured from wave 1. The evaluation included the latent excitation (absolute latency) as well as intercomponent latency (relative latency). The elongation of intercomponent latency 1-111 was looked upon as pathological change, thus pathological changes in the pons were accepted as values being 2.25 ms. But the elongation of latency 111-V evidencing a pathological change in the mesencephalon was taken as over 2.05 ms.

In the evaluation of the therapeutic efficacy, attention was focussed on the number of attacks, the dynamic with which the symptoms regressed after a new attack, the delay in the slowly intensifying course of multiple sclerosis as well as a diminution in intensity of certain neurological symptoms according to a numerical scale (Cendrowski, 1986). This numerical scale is used to estimate the intensity of the individual neurological symptoms in points from 0 to 4. In this way there were estimated pyramid symptoms, cerebellum symptoms, disorder of sensation, sphincters and sight.


Characteristic of patients treated with Padma 28

Age	Menduallary	Cerebellospinal	Dissemination	Total number of patients
20-30	2	2	1	5
31-40	7	19	-	26
41-50	3	11	-	14
above 50	2	3	-	5
Total number of patients	14	35	1	50

RESULTS

The effect of Padma 28 on multiple sclerosis depending on the course of disease is presented in the table.An objective estimation of the improvement or aggravation in multiple sclerosis is difficult. We were estimating the patients' neurological state according to the numerical scale in several trials.
An improvement was reported in 22 patients, i.e. in 44% (Table 2). In 18 of them a diminution of paresis was observed, to the following degree: in 10 of them moderate paresis changed into light paresis (according to the numerical scale from 3 to 2 points); in 5 of them grave paresis reduced to moderate paresis (according to the numerical scale from 4 to 3 points); in 3 of them tight paresis disappeared (reduction from 2 to 1 point). Apart from this, in 3 patients the disorder of sensation, and in 1 subject the ataxy, disappeared.
An assessment of the health of untreated subjects (control group), with the course of the disease being taken into consideration, is depicted in Table 3. lt is obvious from this Table, that among patients who did not receive Padma 28, none of them felt better, while 20 patients (40%) reported deterioration.
The results of treatment with Padma 28, including the age of patients, are shown in Table 4. lt is seen from this Table, that among the subjects over 50 years of age, no deterioration was observed. In other groups, the deterioration occurred most frequently among patients 41-50 years old.

Before the onset of therapy, visual evoked potentials were found to be normal in 26 patients, while 24 subjects demonstrated an elongated latency of the P, wave from 118 to 150ms. At follow-up examination, after the end of therapy with Padma 28, 8 patients showed an improvement expressed by the shortening of P, wave latency.
Examination of the auditory evoked potentials in 30 patients exhibited an abnormal tracing (60%). In 15 of them the intercomponental latency 1-111 was elongated over 2.25 ms; in 10 persons the elongation of intercomponental latency 111-V was over 2.05 ms and in 5 patients there was an elongation of latency 1-111 and 111-V. At control examination upon the termination of therapy the tracing, from 1 patient had worsened, in others the tracings failed to indicate any significant changes.
No side effects were noted. The tolerance of the drug was excellent. Laboratory tests were unchanged in the course of the trial.


Effect of Padma 28 on the course of disease

Courses of disease	Improvement	Result Nochange	Deterioraton	Total Number of Patients
Attacks	15	11	3	29
Progression	7	11	3	21
Total number of patients	22	22	6	50

Course of multiple sclerosis in the control group

Courses of disease	Improvement	Result Nochange	Deterioraton	Total Number of Patients
Attacks	-	20	11	31
Progression	-	10	9	19
Total number of patients	-	30	20	50

Results of the treatement with Padma 28 in relation to age

Age	Improvement	Result Nochange	Deterioraton	Total Number of Patients
20-30	2	2	1	5
31-40	10	14	2	26
41-50	5	6	3	14
above 50	5	-	-	5
Total number of patients	22	22	6	50

DISCUSSION

None of the therapeutic methods in current use has influenced the natural course of multiple sclerosis. In treatment, 180 or so methods and drugs have hitherto been used, and only a small number have overcome the test of time (Wender, 1990).

Several observations suggest that an immunological process is involved in the pathogenesis of multiple sclerosis (Ross Russei and Woles 1985). Although the CNS is normally immunologically projected by the blood-brain barrier, this structure is easily damaged, allowing CNS invasion by systemic immune cells form which the Ig-secreting cells in the brain of patients with multiple sclerosis are derived. Because of the very incomplete understanding of the immunological basis of multiple sclerosis it is not yet certain whether stimulatory or suppressive immunological treatment should be given. Existing trials suggest that immunological treatment can reduce the rate of disability and frequency of relapse even in severely affected patients (Cendrowski, 1980; Halliday and McDonald, 1977; Lowitzsch et al., 1976). Padma 28 is an immunoregulatory drug (Brzosko et al., 1982) improving the function of T suppressor lymphocyte (T,) and thus the function of the immune system. Although this drug has no lymphopoietic activity like thymic hormones, it seems to influence differentiation and maturation of T, lymphocyte lineage. Taking into account the immunoregulatory properties of Padma 28 application of this drug in patients suffering from multiple sclerosis seems to be fully justified.

Padma 28 was administered to 50 patients affected by multiple sclerosis. They included 29 persons, in whom multiple sclerosis proceeded with attacks, and 21 subjects who had a slowly progressing course of the disease. In the first group improvement was recorded in 52% of patients, deterioration occurred in 10% while in 38% the condition remained unchanged. In a similar control group containing 31 persons with attacks of multiple sclerosis, who were not treated with Padma 28, not a single patient experienced improvement, deterioration appeared in about 35%, and in 65% of subjects the course of multiple sclerosis was unaltered. Twenty-one patients with slowly progressing multiple sclerosis were given Padma 28. Seven of them (33%) revealed improvement, in 3 persons (14%) the state worsened, and in 11 subjects (52%) no changes were observed in the course of treatment. In the group of 19 persons with slowly progressing multiple sclerosis, who were not receiving Padma 28, not a single case of improvement was detected, in 9 patients (47%) deterioration took place, and in 10 subjects there was no alteration. It is worth mentioning that in only 3 patients taking Padma 28, attacks of disease occurred and in 4 patients the attack had appeared after the termination of therapy. Thus, it seems to be obvious that Padma 28 exerts a positive effect on the course of multiple sclerosis. In patients treated with this drug, there was improvement as in many as 44% of subjects. Among the 50 control patients with multiple sclerosis, who were not treated with Padma 28, there was no improvement in any of the cases.

Since no publication on the activity of Padma 28 has been available, the results of our studies may be com- pared exclusively with other immunomodulating agents, such as levamisole or thymopentin (Bolla et al., 1984; Wender, 1990). However, while applying Padma 28 no complications were observed. Also all the biochemical tests done before, during the course and after Padma 28 administration, demonstrated that the drug is harmless; no single ease involving internal organ complications was revealed.

In all patients with multiple sclerosis treated with Padma 28, our studies dealt with visual and auditory evoked potentials. The visual evoked potentials play an important diagnostic part in detecting lesions of the visual pathway. They were abnormal, before beginning therapy with Padma 28, in 24 patients. Final examination displayed improvement in 8 subjects, while in 2 persons full normalization of the tracing was noted. As reported by the authors (Lowitzsch et al., 1976; Rossini et al., 1979), during the disease remission period a reduction in previously elongated latencies can be observed. There is a relationship between worsening of the tracings and intensity of the existing or newly forming plaques.

Studies of auditory evoked potentials permit us, to a certain degree, to reach a conclusion as to the state of the structures in the area of the pons and the mesencephalon. In the first study, 60% of patients had an abnormal tracing. Control examination after finishing Padma 28 administration failed to disclose any differences as compared with the initial examination. This observation seems to be consistent with results obtained by other authors (Cendrowski, 1980), who emphasize that in patients with initially abnormal recordings of the auditory evoked potentials, no more pronounced changes were observed during the disease exacerbation or remission.

The results of our studies may be subjective to an extent in that it is known that multiple sclerosis is characterized by irregular periods of disease activity (relapses) lasting from a few days to several weeks, interspersed by intervals of spontaneous remission which may last for a long time.

In conclusion a profitable influence of Padma 28 was observed in 44% of patients with multiple sclerosis in the shape of a reduction of the pyramid symptoms, diminution of the cerebellum symptoms, decrease or disappearance of disorder of sphincters; there was no aggravation of the patients' state during treatment with Padma 28; among patients with abnormal initial visual evoked potentials, in 41% an improvement or normalization of the tracing was obtained, prolonged application of Padma 28 caused no undesirable symptoms- tolerance of the drug was excellent. We therefore believe that Padma 28 may be useful in slowing or arresting the symptoms of chronic multiple sclerosis.

REFERENCES

Bach, M. (1982). Deficit of suppressor T cells in active multiple sclerosis. Symposium on Multiple Sclerosis, Copenhagen.

Badmajew, P., Jr, Badmajew, V., Jr, and Park, L. (1982a). Healing Herbs. Lotus Press, Berkeley.

Badrnajew, V., Jr, Brzosko, W. J., Debrowski, M. P., and Dgbrowska-Bernstein, B. K. (1982b). Padma 28: an irnmu- noregulatory substance in vitro. Abstract of the Second International Conference on lmmunopharmacology, Washington.

Bolla K., Duchateau, J., Delespesse, G., and Servais, G. (1984). Imn-lunomodulation with thymopentin in humans. lnt. J. Pharm. Res. 4, 431-438.

Brzosko, W. J., Badmajew, V. Jr., Plachcihska, J., Dbrowska, M., Debrowska, B., and Loch, T. (1982). Padma 28 a new drug for patients with HBsAg positive or negative chronic aggressive hepatitis. Hepatology, Rapid Literature Review 8, Memo-H-1971.

Brzosko, W. J., Badrnajew, V. Jr, Plachci@ska, J., Beraud, M., Golonko, L., D4browa, A., Krzysztofik, R., and Matacz, D. (1983). Laboratory and clinical studies on Padma 28 (in Polish). lmmunot. Pol. 8, 216.

Brzosko, W. J., Plachciriska, J., Krzysztofik, R., and Nawrocka, E. (1984). Padrna 28, a new drug for patients with ehronic active hepatitis. Hepatology, Rapid Literature Review 14, Memo-zh-2166.

Cendrowski, W. (1980). Cortical and cervical somatosensoric potentials evoked in patients with multiple sclerosis. Neuroi. Neurochir. Pol. 14, 553-557.

Cendrowski, W. (1986). Demyelimating Diseases (in Polish). PZWL, Warsaw.

Halliday, A., and MeDonald, J. (1977). Pathomorphology of demyelinating disease. Br. Med. BulL 33,21-27.

Kuratowska, Z., Lutyhski, A., and Dwilejczyk-Trojanek, J. (1982). Selected Problems of Clinical Immunology (in' Polish). PZWL, Warsavv.

Lowitzsch, K., Kuhnt, U., Sakman, Ch., Maurer, K., Hopf, H., Schott, D., and Thater, K. (1976). Visual pattern evaked responses and blink reflexes in assessment of MS diagno- sis. J. Neurol. 213,17-32.

Ross Russel, R. W., and Woles, C. M. (1985). Neurology. Year Bock, Chicago.

Rossini, P., Pirchio, M., Salluzzo, D., and Caltagirone, C. (1979). Foveal versus peripheral retinal responses: a new analysis for early diagnosis of multiple sclerosis. EEG. Clin. Neurophysiol. 47, 515-531.

Sarnochowiec, L. (1983). Theoretieal, chernical and pharrnaco- dynamical examinations of Padma 28. First International Convention on Tibetan Medicine, Venice, Padma, AG. Zürich.

Samochowiec, L., and W6jcicki, J. (1987). Effect of Padma 28 on lipid endoperoxides forrnation. Herbe Polon. 33, 219-222.

Wender, M. (1990). Demyelinating diseases. In, Treatment of Nervous System Diseases (in Polish), ed. by 1. Hausmanowa-Petrusewicz. PZWL, Warsavv.

Wöjcicki, J., Gonet, B., Samochowiec, L., Gnacitiska, K., and Juiwiak, S. (1989). Effect of Padma 28 on ascorbate system in rats receiving a high-fat diet. Phytother, Res. 3, 54-56.

Reported by Susan Aldridge, PhD, medical journalist

A comparison reveals that women on oral contraceptives are less likely to develop multiple sclerosis.
Previous research has suggested that pregnancy can protect women from developing multiple sclerosis (MS), probably because of hormonal factors. Now a team at Harvard School of Public Health show that oral contraceptives (OCs) have a similarly beneficial effect.

OCs contain the female hormone estrogen and prevent conception by putting the body in an artificial state of pregnancy. In this study, 106 women with MS were compared with 1,001 women who did not have the condition. The comparison revealed that taking OCs was linked to a 40 per cent reduced risk of MS. The researchers believe it is the estrogen content of the OCs which is responsible for this effect. They also found, as expected, that pregnancy was protective of a first attack of MS.

Source
Archives of Neurology September 2005

http://www.healthandage.com/Home/gm=1!gid1=7597

Friday, September 30, 2005


Deputy commissioner says Internet updates part of plan

Thursday, September 29, 2005; Posted: 11:51 a.m. EDT (15:51 GMT)


WASHINGTON (Reuters) -- Prescription drug labels will be easier to read and updated quickly on the Internet as part of an effort being launched later this year to improve information for doctors and patients, a U.S. health official said Wednesday.

Regulators have been promising a major revamp of prescribing instructions for years. Labels for physicians now run several pages and have side-effect information scattered throughout. It can take months for new warnings to be added.

Rules outlining a new format will be issued soon, said Dr. Scott Gottlieb, the Food and Drug Administration deputy commissioner for medical and scientific affairs. He declined to provide details.

"This is an important step toward creating an electronic environment for drug safety and drug effectiveness information that will make it easier for doctors and patients to get up-to-date information right at the point of care," Gottlieb told reporters.

The step is part of a broader program that will begin in November to make important information readily available by electronic means such as over the Internet or through personal digital assistants, he said.

Drug makers will have to submit changes to their product labels electronically starting next month in a standard format that makes updating older versions "seamless and automatic," Gottlieb said.

The agency also is "seriously discussing" releasing regular updates, perhaps weekly, about side effect reports for drugs on the market, he said.

Peter Lurie, deputy director of Public Citizen's Health Research Group, a consumer group, said the ideas were good ones, but noted that the FDA should approve more "medication guides" that explain risks and benefits to consumers in plain English.

"That's the simplest way to inform the patient, to provide them with FDA-regulated and approved information at the time of prescribing," he said.

The FDA has been attacked as being too slow to respond and warn the public about signs of serious side effects from some medicines. Two agency scientists went public with charges that their supervisors downplayed or suppressed their concerns about antidepressants used by children and Merck & Co. Inc.'s recalled arthritis drug Vioxx.

Gottlieb, a practicing physician, also has come under criticism since he took his current FDA post in July following a stint in the private sector, which included editing a Wall Street newsletter that offered tips on health-related stocks.

Time magazine reported some of his e-mails that raised questions about rulings on certain drugs sparked concern that he was trying to steer decisions in an industry-friendly way.

Asked about the charges, Gottlieb said Wednesday: "We are living in an environment now where it's very hard to ask scientific questions of people.

"Every time you ask questions, it's supposed you are trying to second-guess someone's judgment. That's fundamentally unfair, and I don't think the result is going to be more information and better decision-making. I think the result is going to be quite the opposite," he said.

http://www.cnn.com/2005/HEALTH/09/29/fda.drug.labels.reut/index.html

http://tinyurl.com/d87wz

28 Sep 2005
The cannabis based medicine, Sativex®, is effective in reducing central neuropathic pain and sleep disturbance in people with Multiple Sclerosis (MS) in a UK study published today in the medical journal, Neurology 1.

This randomised, controlled trial demonstrates that Sativex® was significantly superior to placebo in reducing the mean intensity of pain (p=0.005) and sleep disturbance (p=0.003) amongst people with MS1.

The study was conducted in 66 patients, 65% of whom required support to walk or were wheelchair bound and were suffering from moderate to severe central neuropathic pain which had not been alleviated by currently available medications. Patients continued to take their existing medication throughout the trial1.

Sativex® was administered as an oromucosal spray allowing flexible dosing which is ideally suited to the variable nature of MS. Sativex® was generally well tolerated in the study, although more patients on Sativex® than placebo reported dizziness, dry mouth and somnolence. Cognitive side effects were limited to long-term memory storage1.

Dr. Carolyn Young, principal investigator and Consultant Neurologist based at the Walton Centre for Neurology and Neurosurgery in Liverpool said, “Central neuropathic pain occurs frequently in people with MS. It can be tremendously debilitating and unresponsive to existing therapies. Our findings demonstrate that Sativex was effective in reducing both central pain in MS and pain-related sleep disturbance in a population with moderate to severe central pain inadequately relieved by existing medication”.

Sativex® has been developed by UK-based GW Pharmaceuticals plc. Sativex® is indicated as adjunctive treatment for the symptomatic relief of neuropathic pain in adults with MS. Health Canada has approved Sativex® with conditions, under the Notice of Compliance with Conditions (NOC/c) policy. This authorization reflects the promising nature of the clinical evidence which will be confirmed with further studies. Products approved under Health Canada's NOC/c policy, have demonstrated promising benefit, are of high quality and possess an acceptable safety profile based on a benefit/risk assessment for the approved use. Sativex® is marketed in Canada by Bayer HealthCare.

About Bayer HealthCare AG

Bayer HealthCare AG, a subsidiary of Bayer AG, is one of the world's leading, innovative companies in the health care and medical products industry. In 2004, the Bayer HealthCare subgroup generated sales amounting to some 8.5 billion Euro.

The company combines the global activities of the divisions Animal Health, Biological Products, Consumer Care, Diabetes Care, Diagnostics and Pharmaceuticals. Bayer HealthCare employed 35,300 people worldwide in 2004.

Bayer HealthCare's aim is to discover and manufacture innovative products that will improve human and animal health worldwide. The products enhance well-being and quality of life by diagnosing, preventing and treating disease.

This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group Management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in our public reports filed with the Frankfurt Stock Exchange and with the U.S. Securities and Exchange Commission (including our Form 20-F). The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

About GW Pharmaceuticals plc

GW Pharmaceuticals plc is licensed by the UK Home Office to undertake a pharmaceutical research and development programme to develop non-smoked cannabis-based prescription medicines. GW's shares are publicly traded on AiM, a market on the London Stock Exchange.

GW's clinical research program is being carried out by a team of pharmaceutical professionals experienced in drug development and, in particular, the development of plant-based medicines and drug delivery systems.

This news release may contain forward-looking statements that reflect GW's current expectations regarding future events, including the clinical development and regulatory clearance of its products. Forward-looking statements involve risks and uncertainties. Actual events could differ materially from those projected herein and depend on a number of factors, including (inter alia), the success of GW's research strategies, the applicability of the discoveries made therein, the successful and timely completion of clinical studies, including with respect to Sativex and GW's other products, the uncertainties related to the regulatory process, and the acceptance of Sativex and other products by consumers and medical professionals.

Alanna Fox
Cohn & Wolfe
Tel: (416) 324-2069 ext. 4078
Alanna_fox@ca.cohnwolfe.com

Lori Ann Horrigan
Bayer Inc.
Tel: (416) 240-5252 or 1-800-440-5473
Lori-ann.horrigan.b@bayer.com

References
1. D.J.Rog, T.J.Nurmikko, T.Friede, and C.A Young. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology 2005;65:812

gwpharm.com/sativex.asp

http://www.medicalnewstoday.com/medicalnews.php?newsid=31242

http://tinyurl.com/a2cly

Prof. Mark Freedman of the University of Ottawa will present at the conference the initial results of a landmark study that successfully predicted impending disease activity in multiple sclerosis (MS) patients using technology developed by Glycominds Ltd.

For the first time researchers have shown that it is possible to predict, using a blood test, whether or not a patient will imminently develop an active form of MS, after the first neurological event.

"Neurologists have been struggling with a decision to initiate or not disease modifying therapy after only a single attack of what might be MS," said Prof. Mark Freedman, the principal investigator of the study known as PRACTIMS (Prognosis and Response of Anti-Carbohydrate Titer In MS). "Knowing at this earliest timepoint that a patient is destined to develop active disease would greatly assist this decision," he added.

The MS predictor test is a simple blood test based on novel biomarkers to indicate the likely course of a patient's condition.

The study results show that the Glycominds technology was able to correctly predict the future course of the disease in patients, on the basis of retrospective blood samples taken from 90 patients after their first neurological event.

The Glycominds test correctly identified in advance the 36 percent of patients who later on suffered additional clinical events in the two year period following their first symptoms.

Currently, doctors are unable to tell if a patient who has suffered a single neurological event will develop a mild or active form of the devastating disease. Consequently many people who do not require treatment, find themselves on life-long therapy regimens which may be expensive, cause adverse side effects and leave them in a perpetual state of anxiety. At the same time, many MS patients do not receive the more aggressive therapeutic intervention they may require because doctors are uncertain of whether they will continue to have an active disease.

"Glycominds next plans to validate externally these results on thousands of retroactive patient samples and to bring this product to market during 2006," said Avinoam Dukler, CEO of Glycominds.

The dramatic results of the current study have been judged important enough to be included as part of the "late-breaking news" section on Oct. 1 of a major scientific conference, the 21st Congress of the European Committee for the Treatment and Research in Multiple Sclerosis and the 10th Annual Meeting of the American Committee for Treatment and Research in Multiple Sclerosis taking place in Thessaloniki, 28 September - 1 October 2005.

Multiple Sclerosis: Background

Multiple Sclerosis is the second most common cause of neurological disability in young adults, generally during their late 20's and 30's, and striking twice as many women as men. The nature of the disability, its extent, and the speed of progression can vary greatly from person to person. A reliable and validated test for disease staging and monitoring does not currently exist.

Some patients with MS initially present with a clinically isolated syndrome (CIS) but the course of the disease is unpredictable at its onset. The disease may progress rapidly or remain inactive for many years. A simple serological test that predicts whether patients with a CIS suggestive of MS or newly diagnosed relapsing remitting MS patients will have a highly active or more benign disease course would enable patients to receive the appropriate treatment sooner.

About Glycominds

Since being founded in 1999, Glycominds has developed a portfolio of complementary technologies which enable the reliable and accurate study of sugar biomarkers. The company's IBDX(TM) kits, a series of blood tests for Crohn's Disease differential diagnosis has received the CE MARK and was recently launched in Europe.

For more information visit www.glycominds.com
http://www.rednova.com/news/health/253716/study_shows_glycominds_test_may_predict_active_multiple_sclerosis/index.html?source=r_health

http://www.yaledailynews.com/article.asp?AID=30043

BY REBECCA YERGIN
Contributing Reporter

Each year around 2.5 million people world-wide, including 400,000 Americans, are affected by multiple sclerosis, a crippling disease that targets the brain and spinal cord. While the exact causes for this disease remain unknown, recent research by the Yale School of Medicine and the University of Connecticut Health Center brings scientists one step closer to finding a cure.

The study, co-authored by Nancy Ruddle, director of graduate studies for epidemiology and public health at Yale, and University of Connecticut professor Stephen Pfeiffer, was published in last week's "Proceedings of the National Academies of Science." The team was successful in distinguishing between antibodies that do and do not contribute to the disease, but the two researchers said there is a long way to go before multiple sclerosis can be fully understood and prevented.

"Research like this is a little piece to a larger puzzle," Pfeiffer said. "[Finding a treatment] will not happen in one big flash. A treatment will be the development of a gradual accretion of many people's work."

Both Pfeiffer and Ruddle said the collaboration and information exchange between the two labs was crucial to their success.

Pfeiffer and Ruddle are two of many scientists across the world working on multiple sclerosis, a chronic autoimmune disease in which the body attacks the insulating material surrounding nerve cells. Without this insulation, called myelin, information cannot travel as fast, resulting in ascending paralysis and impaired physical mobility.

Because the disease is chronic, Ruddle said such symptoms usually develop later in life, at which point little can be done to prevent future degeneration. Thus, researchers must identify the causes of multiple sclerosis and treat the disease in its early stages to prevent it from seriously damaging the body.

"MS is the most common neurological crippler of young adults in our society," said Stephen Waxman, chair of Yale's Neurology Department. "We need to learn more about it so we can cure it. Nancy and Pfeiffer have taken an important step forward."

Pfeiffer, who has been studying multiple sclerosis since 1970, and his team observed the biology of myelin-producing cells and the changes antibodies associated with multiple sclerosis induce in these cells. They then injected two types of antibodies -- those known to contribute to multiple sclerosis and those known not to contribute -- to better understand the workings of the disease.

This process, which began a few years ago, did not always procure sufficient results, Pfeiffer said.

"[In research like this] your heart can be broken for months," he said, "and then suddenly you see something that works. Then in a flash [your work] becomes the most exciting thing in the world."

For Pfeiffer's lab, the excitement came with discovery that the antibodies reacted with a specific molecule, known as MOG, on the surface of myelin cells, he said. After this discovery Ruddle's lab took a more clinical approach, using mice models to learn more about how antibodies cause multiple sclerosis.

Ruddle's team studied the animal version of multiple sclerosis, known as EAE -- both diseases target myelin and affect extremities. While the human disease is chronic, mice experience an acute form that lasts less than two weeks.

Ruddle injected the animals with components of both human and rat MOG. They discovered the antibodies that cause multiple sclerosis recognize MOG on the cell surface and can change the MOG-making cells, while benign antibodies only recognize MOG inside the cell and cannot alter the MOG-making cell, Ruddle said.

Ruddle and Pfeiffer said their findings show promise but are not a clinical end in themselves. Pfeiffer said there is no definite timeline or course for the development of a multiple sclerosis cure, but further teamwork and collaborations will be needed to beat the disease.

NEW YORK - The single biggest issue that is significant enough to drive a double in Elan over the next two to three years is this: Will the FDA approve Tysabri for use in mono-therapy after Elan pulled it from the market?

We surveyed more than 1,500 members of Marketocracy who put Elan (nyse: ELN - news - people ) in their virtual portfolios to try to flesh out the answer. Three interesting perspectives emerged from the responses.

The FDA: For the U.S. Food and Drug Administration, the question of whether to allow Tysabri back on the market is one of benefits and risks. The main benefit is that two-year clinical studies have shown Tysabri, when used alone, is twice as effective as any other approved drug in preventing relapses. People who have used Tysabri have actually got out of their wheelchairs.

The main risk is that three patients have come down with a potentially fatal complication called progressive multifocal leukoencephalopathy, or PML--two have died. That's a complication rate of 0.1% out of 3,500 patients. All three cases involve patients taking Tysabri in combination with Avonex from Biogen (nasdaq: BGEN - news - people ). Since the three PML cases were discovered, 91% of the patients in Multiple Sclerosis clinical trials that took Tysabri have been screened for PML, and no additional patients have showed signs of contracting it. There has not been a single case of PML when Tysabri was used alone, but Elan voluntarily took it off the market.

The bottom line is the drug sets the gold standard for efficacy in a disease that is very nasty. Patients want this drug available because it is effective. I expect the FDA will decide that its benefits offset its risks--especially for patients for whom all existing drugs have failed.

Patients, Doctors and Caregivers: MS patients and the people who care for them understand that treating powerful diseases requires commensurately powerful drugs, and they understand that, because of potency, the drugs have potentially fatal consequences for some at-risk patients.

For almost 25% of MS patients, existing drugs have failed to be effective, so many have stopped taking any MS drug at all. Tysabri could be their best option. Most of the remaining MS patients report that the drugs they take do not work well. At best, they slow the progression of the disease, but there is a high relapse rate and many side effects.

So, given the almost 100% certainty of the progressive debilitating effects of the disease, most patients would opt for the rare possibility of PML if they could halt the progress of MS and improve the quality of their lives. A particularly poignant response I received was: "I participated in the AFFIRM trials and had Tysabri for nearly three years. I forgot what it was like to be an "MSer." Since Feb. 28, nearly all of my most annoying symptoms (itching, fatigue, brain fog) have returned, and I have had my first relapse in about four years."

Biogen: Biogen, the U.S. distributor for Tysabri, also owns a best-selling MS drug called Avonex. Typically, a drug has to be proved effective as mono-therapy before it is approved for combination therapy. Biogen pushed Tysabri's use in combination with Avonex, hoping to convince doctors to prescribe two drugs instead of one. Taking on Biogen as a partner created a conflict of interest.

With FDA approval of Tysabri in combination with Avonex looking remote, Biogen's next-best alternative is to return Tysabri to the market as quickly as possible. As a result, Biogen's interests are now much more aligned with Elan's.

Approval by the FDA of Tysabri for use in mono-therapy by the 20% to 25% of MS patients that have already given up on all other drugs would drive a double in Elan's stock price. Based on the feedback we've received from the people who are in the best position to judge, we believe that will happen. And if any of the remaining MS patients decide to give up on the less-effective drugs they are currently using to try Tysabri then Elan will do even better.

http://www.newsletters.forbes.com/DRHM/servlet/ControllerServlet?Action=DisplayMainPage&SiteID=es_764&pgm=241400

Biogen files to bring Tysabri back to market

By Jeffrey Krasner, Globe Staff | September 27, 2005

Biogen Idec Inc. said it has submitted an application to the US Food and Drug Administration seeking a revised license so it can put its multiple sclerosis drug Tysabri back on the market.

The Cambridge company said the application contained the results of its extensive safety review of Tysabri use by multiple sclerosis patients and trial participants, and ''nearly complete" results of its safety review of participants in trials for Crohn's disease and rheumatoid arthritis.

''We are grateful to the MS community for their patience and support over the last several months while we've conducted an extensive safety evaluation of Tysabri in collaboration with leading experts," said Burt Adelman, Biogen Idec's executive vice president of development, in a statement. ''We look forward to working with regulatory authorities during the review process, and ultimately, we hope to provide Tysabri to people living with MS."

A Biogen Idec spokeswoman said the company asked the FDA for accelerated review of the application. If granted, the FDA could respond to the application within six months, rather than 10. A decision on the accelerated review request is expected within 30 days.

Biogen Idec and its partner Elan Pharmaceuticals of Ireland in February voluntarily pulled Tysabri off the market and discontinued clinical trials. One patient taking the drug had died of a rare brain disease and a second was suspected of having contracted it. That patient recovered. A third case of the disease was discovered among patients who had taken the drug for Crohn's disease, an intestinal ailment.

Since then, Biogen Idec has been scouring the records of patients who took Tysabri in clinical trials and during its time on the market. It said it hasn't found any other cases of the brain disease.

Analysts believe Biogen Idec will seek to restart Tysabri sales with a new warning label. Amy Brockelman, a company spokeswoman, declined to comment on the proposed labeling language. ''It's premature to comment on the specifics of the label while we're in discussions with regulatory authorities," she said.

Biogen Idec also filed similar safety review data with the European Medicines Agency. Tysabri hasn't been approved for sale in Europe and the new information will be added to the company's pending application.


© Copyright 2005 The New York Times Company

22 Sep 2005
http://tinyurl.com/b5aws

A cluster of genes on chromosome six is the only one that plays a significant role in multiple sclerosis (MS), according to the most complete genetic study to date in the disorder, presented at the 130th annual meeting of the American Neurological Association in San Diego.

"Our results confirm the strong role of the major histocompatibility complex genes in MS, and provides a definitive statement that no other region of the genome harbors a gene with a similar overall influence on MS genetics," said Jonathan Haines, Ph.D, of Vanderbilt University in Nashville, Tennessee, who presented on behalf of the International Multiple Sclerosis Genetics Consortium.

"A detailed examination of the major histocompatibility complex is critically important," said Haines, who suggests that this study may have profound implications for the future directions of MS genetics research.

The major histocompatibility complex (MHC) is a cluster of genes that play a critical role in the recognition of cells in the body as belonging to the body, i.e., not intruders such as bacteria or other pathogens.

When this system of recognition breaks down, the immune system may mistakenly launch an attack against cells, as happens in MS. Researchers believe that some genetic variations in MHC genes make people more susceptible to whatever environmental causes also contribute to MS.

Haines is one of the founders of an international team of researchers from many institutions that collected genetic data on 730 families with more than one case of MS from Australia, Scandinavia, the United Kingdom, and the United States.

Previous studies have implicated the MHC, but also regions on other chromosomes, as harboring genes that increase MS risk. Haines suggests that these studies failed to include enough subjects.

"This is the largest genetic linkage study on MS, and the first to be done using the latest technology, which provides very detailed coverage of the entire human genome," said Haines. "Other genes may still play an important role in MS, but finding them will require using new genomic techniques."

Multiple sclerosis is an enigmatic disease of the nervous system and results in the loss of myelin, a substance that normally insulates nerve fibers and speeds electrical conduction through the fibers. Patches of inflammation (known as 'plaques') occur throughout the brain and spinal cord resulting in the loss of myelin and sometimes the nerve fibers themselves.

Depending on which nerve fibers are hindered, patients can experience problems ranging from weakness and clumsiness to numbness, visual disturbances, and even emotional and intellectual alterations. In some patients, MS manifests itself in cycles of relapse and remission and patients may show little sign of the disease between attacks.

[Background/Abstract]

A high density screen for linkage in multiple sclerosis Jonathan L. Haines, Ph.D. (presenting on behalf of the International Multiple Sclerosis Genetics Consortium - IMSGC).
Nashville, TN

This abstract describes the results of what we would consider to be the definitive multiple sclerosis linkage screen. The power of the study is so great that it is virtually certain that all susceptibility loci with effects large enough to be detectable by linkage have been found. The value of a definitive reliable linkage map cannot be overemphasized. The results from this study have profound implications for the future study of the genetics of this complex disorder and enable accurate minimum requirements to be determined for future studies. This is clearly a critical development in the field.

Ten centimorgan microsatellite map have been the standard tool used for whole genome linkage screening since the mid 1990's and to date 11 screens employing this methodology have been published in multiple sclerosis. However the scale and quality of the data in these studies is limited. In order to establish a definitive linkage map we have typed 4506 single nucleotide polymorphism markers in a set of 730 multiplex families from Australia, Scandinavia, the United Kingdom and the United States, which together provide 945 affected relative pairs. Highly significant linkage is observed in the region of the Major Histocompatibility Complex (lod score 11.7) and suggestive linkage is identified on chromosome 17 and 5. Ordered Sub-set analysis identifies a further locus on chromosome 19. The mean information extraction provided by the marker panel is 79.3% (range 42.4 - 91.3%) and the observed Mendelian inconsistencies suggests that within this data set the genotyping error rate is just 0.002%. These data have profound implications for the future directions of multiple sclerosis genetics research and suggest that previous efforts in this area are almost all substantially underpowered. In the future association studies will need to include at least 500-1000 cases.
http://www.medicalnewstoday.com/medicalnews.php?newsid=30970
Crystal Weinberger
anameeting@llmsi.com
American Neurological Association
http://www.aneuroa.org