Medical Letter on the CDC & FDA, May 23, 2000 pNA

2000 MAY 23 - (NewsRx.com) --

A new survey by the Pharmaceutical Research and Manufacturers of America (PhRMA) found 217 medicines and vaccines in development for children.

The survey also found that 25 medicines for children have been approved by the U.S. Food and Drug Administration in the past year, and that companies will soon begin clinical trials on an additional 52 potential medicines for children.

The survey found 48 medicines in development for cancer, the leading disease killer of children; 14 for asthma, which has seen both rising death rates and increased incidence among children in the past decade; nine for AIDS and AIDS-related disorders, which have afflicted some 12,000 American children; and seven for cystic fibrosis, the most common fatal genetic disease in Caucasians in the United States.

In addition, companies are working on new treatments to help children with heart disease, diabetes, eye disorders, Crohn's disease, sickle cell disease, Duchenne's muscular dystrophy, ear infections, pneumonia, cerebral palsy, Tourette's syndrome, psychiatric disorders, transplant rejection, autism, and other conditions.

"The survey shows that medicines for children are a very active area of pharmaceutical research, despite the many practical, legal, and ethical difficulties of testing medicines in children," said Holmer. "In 1997, Congress set up a program to provide incentives for studying medicines in children. The 217 medicines in development show that the program is working extremely well; it should be extended beyond the 2002 sunset to encourage even more clinical research that will bring benefits for our children."

This article was prepared by Medical Letter on the CDC & FDA editors from staff and other reports.

Copyright 2000, Medical Letter on the CDC & FDA via NewsRx.com.

COPYRIGHT 2000 Charles W. Henderson

Marketletter, May 22, 2000 pNA

Layton BioScience has been granted US Food and Drug Administration approval to investigate the nicotinic receptor antagonist Inversine (mecamylamine), which is marketed for the treatment of hypertension, for various neurological disorders, including Tourette's syndrome.

COPYRIGHT 2000 Marketletter Publications Ltd.

PR Newswire, May 15, 2000 p2177

Layton Has Active Research Program in the Area of Nicotinic Antagonists

SUNNYVALE, Calif., May 15 /PRNewswire/ --

Layton BioScience, Inc., a biotechnology company that specializes in developing innovative therapies for neurological disorders, has received approval from the United States Food and Drug Administration to reintroduce Inversine(R) (mecamylamine HCl) to the U.S. market.

Inversine(R), a nicotinic receptor antagonist, was formulated for the treatment of hypertension. Launched in the 1950s, Inversine (R) was one of the first orally active antihypertensives on the U.S. market. "Inversine has a long history of use, almost a half century," states Gary Snable, Layton's chief executive officer. "We believe our studies will show that it has applications for treating a number of neurological disorders."

Currently, Layton is studying Inversine(R) for use in treating symptoms of Tourette Syndrome (TS), which include motor and vocal tics and mood disorders. A case report on the use of Inversine(R) to treat Tourette Syndrome was published in The Lancet in August 1998, and a two-year retrospective study will be published this June in the Journal of Child and Adolescent Psychopharmacology. A new, 18-month study on the use of Inversine(R) in combination with neuroleptic medications is scheduled to begin later this year at the University of South Florida and the University of Florida.

In March, the University of South Florida and researchers Archie A. Silver, M.D., Paul R. Sanberg, Ph.D., D.Sc., and R. Douglas Shytle, Ph.D., received United States Patent #6034079 for the use of nicotine antagonists to treat nicotine-responsive neuropsychiatric disorders. The patent stems from earlier research they conducted with the nicotine patch. Layton has an exclusive, worldwide license to develop therapeutics based on the patent.

In addition, Layton has an active discovery program focusing on finding new chemical entities selective for the nicotinic receptors that are designed to provide targeted and increasingly effective new medications. Layton also has clinical programs focused on the use of nicotinic receptor antagonists in the treatment of addictions (nicotine, cocaine and alcohol) and other neuropsychiatric indications.

Layton BioScience, Inc., with offices in Sunnyvale, Calif., and Radnor, Pa., is a biopharmaceutical company devoted to developing therapies for treating diseases of the central nervous system and neuropsychiatric disorders. The company is currently conducting clinical trials on stroke patients with its stem-cell-like LBS-Neurons(TM), and has obtained the exclusive license to engraftable human neural stem cells, which have applications for global disorders such as Alzheimer's disease. Layton's network of scientists in universities across the United States are researching therapies for other debilitating diseases such as spinal cord injury, brain tumors, Parkinson's disease, Huntington's disease and Tay-Sachs disease.

For more information, visit: www.laytonbio.com and www.tourettehelp.com.

CONTACT: Randy Mintz, 215-790-4361, or Denise Portner, 215-790-4395, or abushman@tierneygroup.com, both of The Tierney Group for Layton BioScience, or Robert Alonso of Layton BioScience, 610-975-9290, or R_alonso@ix.netcom.com.

COPYRIGHT 2000 PR Newswire Association, Inc.

American Medical News, March 20, 2000 v43 i11 p33

Evidence is mounting that nicotine's effect on neurotransmitters may offer promise for treatment of some diseases.

Washington (AP) THE SAME NICOTINE that makes cigarettes so addictive may also have a good side: It shows promise against Parkinson's disease and a variety of other brain conditions, researchers have found.

In a variety of studies reviewed at an American Assn. for the Advancement of Science conference last month, researchers said the evidence is mounting that nicotine can relieve symptoms by changing the way the brain uses neurotransmitters.

Researchers are testing nicotine patches for neurological diseases in both children and the elderly; drug companies are competing to develop nicotine substitutes that have fewer side effects.

At the conference, doctors said the field's first gold-standard study -- one in which placebos are rigorously compared with the real thing -- suggests the patch shows promise in children with Tourette's syndrome.

Still, nicotine has many drawbacks, including its reputation as the addictive grabber in cigarettes. Some experts believe nicotine's real future is in fake forms of the drug.

"The problem with nicotine is that it is nicotine. You're asking parents to put their kids on nicotine," said Paul R. sanberg, PhD, DSc, of the College of Medicine at the University of South Florida, Tampa, who has tested the drug on more than 100 young patients with Tourette's.

Typically, doctors treat Tourette's with the tranquilizer haloperidol. In the latest study, Dr. Sanberg and colleagues combined nicotine patches and haloperidol in 70 children, half of whom got placebo patches.

The study found those on nicotine did better and were able to control their symptoms with lower than usual doses of haloperidol. "The data suggest that a low-dose nicotine patch may be useful in Tourette's syndrome," Dr. Sanberg said.

The researchers cautioned that smoking is a bad way to get medical nicotine. Besides the obvious cancer risk, drug levels spike much higher in cigarettes.

They also say more research is needed before nicotine patches become routine to treat diseases. However Dr. Sanberg said that if patients with Tourette's cannot control their symptoms with standard drugs, a low-dose patch might be worth trying.

Nicotine has been tested for many years in small-scale experiments against Alzheimer's disease and more recently against Parkinson's disease.

Paul Newhouse, MD, of the University of Vermont, Burlington, tried nicotine patches on 15 patients with Parkinson's. Although there was no comparison group, his pilot study suggested that nicotine substantially improved the patients' movement and relieved their mental difficulties.

Dr. Newhouse also tested a synthetic form of nicotine, Abbott Laboratories' ABT-418, on six patients with Alzheimer's Despite the small sample size, Dr. Newhouse said patients showed "a significant improvement in verbal learning and memory" on standardized tests.

Because no drug firms have exclusive rights to nicotine, drug companies have little interest in paying for studies to prove its health benefits. However, several are working on nicotine substitutes that can be patented. These drugs could be more precisely targeted against specific disorders, carry fewer side effects and be available as pills rather than patches.

Nicotine is thought to work by regulating the brain's levels of message-carrying chemicals, such as dopamine and acetylcholine. Researchers said they've seen no sign of patients getting hooked on the patch. The main side effects are nausea and itching around the patch.

Another drawback of the patch is the possibility it might trigger heart attacks, as the much higher nicotine content in cigarettes can. Dr. Sanberg said in his studies, children's heart rates rise about 10% but no other obvious heart effects are shown.

COPYRIGHT 2000 American Medical Association

Time, March 6, 2000 v155 i9 p84

By Horowitz, Janice M.

Full Text

NICOTINE FIT No one wants to say anything good about nicotine, but the highly addictive chemical may in fact have some benefits. A preliminary study of 100 children with Tourette's syndrome--a bizarre affliction in which patients involuntarily grimace, shout obscenities, even bark--finds that those given nicotine patches along with standard medication (the tranquilizer Haldol) had fewer symptoms than kids on placebo patches. And though some young users complained of side effects like nausea, none got hooked.

ATTENTION! Using a special MRI technique, researchers have mapped out regions of the brain involved in paying attention. The frontal cortex and parietal cortex--in the front and back of the brain, respectively--appear to light up when subjects focus on certain signals. Then, as the new stimuli are processed, the visual cortex in the lower rear of the brain moves into action. The finding may help researchers better understand attention-deficit/hyperactivity disorder and even schizophrenia.

BAD NEWS

FORGET ESTROGEN? It looks like estrogen may not be an effective treatment for Alzheimer's, after all. Doctors had every reason to believe it might be; studies show it may prevent the brain-deteriorating disease, and several preliminary reports suggested it could actually be used to treat it. But now the largest and longest study on the subject--100 women with mild to moderate Alzheimer's who took estrogen for a year--finds that the drug did nothing to improve patients' memory, attention span or language skills.

HEARTBREAK HOTELS Warning: more than 80% of cribs in U.S. hotels may be unsafe. Spot checks revealed a variety of hazards, including cribs with soft bedding or adult-size sheets (both known suffocation risks) and cribs with gaps between the mattress and frame that could entrap a baby. Also, about half of mesh-sided cribs checked had holes big enough for infants to get stuck in. What to do? Call ahead and insist that cribs are in good repair.

--By Janice M. Horowitz

Sources: Good News--Amer. Association for the Advancement of Science; Nature Neuroscience (3/00). Bad--J.A.M.A. (2/23/00); U.S. Consumer Product Safety Commission and National Safe Kids Campaign

COPYRIGHT 2000 Time, Inc.

Psychopharmacology Update, March 2000 v11 i3 p8

# Patients: 1 man, 43 y/o

Medication: olanzapine (Zyprexa)

Comments: This patient with schizophrenia and substance dependence had begun taking antipsychotic drugs at age 25. The most often used drug was chlorpromazine (Thorazine), up to 1,000 mg daily for about 14 years. At age 35, the patient began noticing involuntary movements such as excessive blinking and facial grimacing. He also made gasping or barking sounds. He was diagnosed with tardive dyskinesia and possible late-onset Tourette's syndrome. He was started on risperidone (Risperdal), but after two years of therapy (6 mg daily), he still experienced involuntary movements. His risperidone therapy was tapered, and he was given olanzapine, which was increased to 15 mg at bedtime. After six weeks, the patient experienced a marked decrease in involuntary movements and grunting. His tardive dyskinesia improved further after seven months, with only mild involuntary jaw movements. The authors say the patient's improvement was likely a result of switching to olanzapine.

COPYRIGHT 2000 Manisses Communications Group, Inc.

Marketletter, Feb 28, 2000 pNA

Researchers from the US National Institute of Aging have found that estrogen replacement therapy does not improve mental functioning in patients with postmenopausal women with Alzheimer's disease, according to data published in the Journal of the American Medical Association (February 23). Meantime, the American Association for the Advancement of Science meeting has been told that nicotine may be effective in treating several psychiatric disorders, including AD, Parkinson's and Tourette's syndrome, reports the Financial Times. However, the nicotine was not delivered via a cigarette, but rather using low-dose gum, patches or injectable formulations.

COPYRIGHT 2000 Marketletter Publications Ltd.

United Press International, Feb 21, 2000 p1008052u5197

WASHINGTON, Feb. 21 (UPI)

Researchers say preliminary studies show nicotine and nicotine-like drugs can improve behavior and performance in patients with Parkinson's disease, Tourette syndrome and Alzheimer's disease.

"During the past decade we have been seeing that there may be beneficial effects of nicotine in neuropsychiatric diseases," said Paul Sanberg, professor and chairman of neuroscience at the University of South Florida, Tampa, at the annual meeting of the American Association for the Advancement of Science in Washington on Monday.

Sanberg and colleagues presented several studies that showed how nicotine, a nicotine-like high blood pressure medication and experimental nicotine-like substances seemed to help patients

"None of us advocate smoking," said Sanberg. All the studies involved delivering the drugs through intravenous infusions or with patches that allow absorption of the drug through the skin. In many cases, the patches used in the studies are similar to those which can be purchased over the counter.

But the study results are preliminary, and the numbers of patients involved are small, the researchers said. "On the basis of these studies, it is really too early to recommend the use of these patches for patients with these disorders," said Dr. Paul Newhouse, director of the Clinical Neuroscience Research Unit in the Department of Psychiatry at the University of Vermont College of Medicine, Burlington. "It would be a bit rash to suggest that people buy these patches without long-term studies."

The researchers reported:

--In Parkinson's disease, Newhouse treated 15 patients with varying levels of intravenous nicotine, nicotine plus the oral blood pressure medication mecamylamine or placebos. The patients were then placed on nicotine patches for two weeks.

"Nicotine appeared to improve performance speed in all three clinical performance tasks. In most cases, improvement appeared to persist after drug withdrawal, although there was some evidence for the beginning of a return towards baseline (condition at the start of the trial) values at the session two weeks after drug withdrawal," Newhouse said.

He said some patients continued to use the patches after the trial, and he received at least one anecdotal report on continued success.

--In Alzheimer's disease, Newhouse administered the investigational drug ABT-418 through a patch system to seven patients. ABT-418 is very similar in structure to nicotine. He said the results showed a marked improved in memory among the patients.

"The results were very robust," Newhouse said. "If the results were not so robust, I couldn't have gotten the paper published with only seven patients." He said some patients nearly doubled their recall ability and were able to reduce the numbers of mental errors in cognition.

--In Tourette syndrome, Sanberg said administering nicotine patches to children age 8 to 17 resulted in improvement in conduct and reduction in the number of physical and verbal tics associated with the disorder. The 70 children in the study were also taking other medication.

In a study in which children were given either nicotine or dummy patches in addition to medication already being taken, Sanberg noted an 80 percent reduction in motor tics, verbal tics and behavioral problems.

Paradoxically, the researchers said, adding nicotine improved concentrations of neurotransmitters in conditions such as Parkinson's and Alzheimer's to help those patients, but decreased levels of these chemicals' crucial brain messaging in Tourette syndrome.

"We have not seen any addiction problems with the use of the patches," Sanberg said. "Nicotine addiction seems to be based on the mode of administration -- smoking." However, the patches caused side effects such as nausea, or itchiness at the patch site.

Newhouse said: "The patch by itself is not reinforcing for addiction. You don't see kids at school trying to score nicotine patches."

Sanberg said the studies on nicotine were originally funded through tobacco-related institutes, but now the research is funded by the National Institutes of Health, and through non-profit organizations such as those aimed at aiding Tourette's patients.

(c) 2000 UPI All rights reserved.

Copyright 2000 by United Press International.

Drug Is Safe for Kids with Tourette's Syndrome

February 24, 2000
Reuters Health

NEW YORK, Feb 24 (Reuters Health) -- A drug known as ziprasidone can safely reduce symptoms in children with Tourette's syndrome, a condition characterized by uncontrollable facial grimaces, tics, and involuntary grunts, snorts and shouts.

Although the drug is "somewhat less" effective than traditional drugs used to treat children, it may be more tolerable than other medications, according to Dr. Phillip B. Chappell, from Pfizer Central Research, in Groton, Connecticut, and colleagues. Tourette's is often treated with antipsychotic drugs, which may cause side effects such as sedation, restlessness or in rare cases, tremors or uncontrollable movements.

In a new study, the researchers gave ziprasidone or an inactive placebo drug to 28 patients, aged 7 to 17 years.

Ziprasidone reduced tic severity by 35% compared with placebo and reduced tic frequency by nearly 50%, according to the report in the March issue of the Journal of the American Academy of Child and Adolescent Psychiatry.

The most common side effect of ziprasidone was drowsiness, which resolved when the dose was reduced. Only one patient developed restlessness at the highest dose, which also tended to improve when the dose was reduced. No patients developed tremors or muscle stiffness, which have been associated with drugs used to treat Tourette's.

Ziprasidone also did not cause weight gain or sustained increases in certain hormones, important side effects associated with other treatments for Tourette's syndrome in children and adolescents, according to the authors.

Ziprasidone also reduced symptoms of obsessive-compulsive disorder by an average of 26% in patients with the disorder, according to the report. The finding was "intriguing," Chappell and his team say, and further studies should be conducted to look at the drug in patients with combined obsessive-compulsive disorder and Tourette's syndrome.

SOURCE: Journal of the American Academy of Child and Child Adolescent Psychiatry 2000;39:292-299.