What's Hot

What's Hot

June 2000

What's Hot Archive

June 30, 2000

Urine test developed for Alzheimer's marker

Alzheimer's disease effects an estimated twenty million people worldwide. As reported in our What's Hot section for June 22, confirmation of an Alzheimer's disease diagnosis has had to wait until autopsy when the brain can be examined. Even postmortem diagnosis has been shown to be only 82 to 92% reliable. The journal Neurology recently reported a study which confirmed the elevation of a protein, AD7C-neuronal thread protein (NTP), in the cerebrospinal fluid of Alzheimer's disease patients, which was positively associated with the severity of symptoms. Thirteen other studies have documented the significance of this protein in the disease. Based on the observation that Alzheimer's patients who have high levels of the protein have increased gold particle migration, Nymox Corporation has developed a urine test which will soon be available, that measures gold migration when the patient's urine is treated with a gold-containing compound.

Suzanne de la Monte and Jack Wands of Massachusetts General Hospital discovered NTP associated with neurofibrillary tangles in Alzheimer's patients' brains. The protein may be produced in response to degeneration of the brain, as it could promote the growth of neurons.

Early, accurate diagnosis of Alzheimer's disease will enable the patient to benefit from drugs available to treat the condition, delaying the damage that can lead to institutionalization. Until now, a diagnosis of Alzheimer's disease typically took three years from the onset of symptoms. "This is an exciting development and an important milestone. We will be moving as rapidly as possible to scale up manufacturing in order to fulfill regulatory requirements and to make the test available for sale as soon as possible where permitted," stated Dr. Michael Munzar, Medical Director of Nymox and President of Serex, Inc.

—D Dye


June 28, 2000

Human genome project completed

In what has been compared in magnitude of significance to man's walking on the moon, the announcement was made Monday of the completion of mapping the first draft of the entire human genome. This milestone in technological achievement was the result of a rush to the finish by two competing teams, one publicly funded and one private, to identify the composition of human DNA. Present at Monday's White House ceremony in honor of the event were President Clinton, Human Genome Project Director Francis Collins, and Nobel laureate James Watson, codiscoverer of the structure of DNA nearly half a century ago.

The set of instructions for making an organism is its genome. It is found in the nucleus of each cell and consists of DNA (deoxyribonucleic acid ), which is organized into chromosomes. Human DNA consists of 3.12 billion base pairs of nucleotides, which make up an estimated 30,000 to 200,000 genes. One of the accomplished project goals was drafting the particular order of the base pairs, which are composed of the nucleotides adenine, thymine, cytosine and guanine.

Up to ten percent of the genes encode proteins which perform various functions. Only approximately 0.1% of our genetic heritage is what makes us unique individuals; the remainder is shared by all humans. Director of the Whitehead Center for Genome Research, Eric Lander, stated, "The next step is a mad rush by companies all over the world to locate every single gene inside the mall, because these genes are the most valuable resource of the 21st century."

The ability of medical science to identify human genes offers tremendous potential. Advancements in gene therapy, the development of gene chips which can measure gene activity, and greatly improved diagnostic methods are among the many anticipated benefits. As further research proceeds, individuals will be able to know in advance whether they are genetically predisposed to diseases ranging from schizophrenia to cancer, and can avail themselves of drugs targeted to their conditions.

Project Director Collins announced, "Today we celebrate the revelation of the first draft of the book of human life . . . We have caught a glimpse of an instruction book previously known only to God."

—D Dye


June 22, 2000

Premortem test for Alzheimer's

A current hypothesis for the development of Alzheimer's disease sets forth that a protein called amyloid-beta is increasingly produced, resulting in plaques found in the brains of patients diagnosed with the disease. These plaques trigger an inflammatory response that leads to the death of brain cells, causing the memory loss and dementia typical of the disease. The plaques are not well visualized with current medical imaging devices. A new test has been developed for Alzheimer's disease that allows early diagnosis, and visualization of senile plaques. Confirmation of an Alzheimer's diagnosis has had to wait until examination upon autopsy. Doctors have had no way of evaluating the efficacy of current treatments because of an inability to examine the targeted senile plaques.

The June 20, 2000 issue of Proceedings of the National Academy of Sciences reported on the development of a compound by the Pennsylvania School of Medicine that can cross the blood brain barrier and label senile plaques. The compound, called BSB, is highly fluorescent, therefore able to be visualized by fluorescent microscopy, and could be radiolabeled so that the plaques are visible upon CT or PET scans. The compound was studied on postmortem human brains and in mice. BSB was effective in mice when injected into the brain and also traveled to the brain, penetrating the blood brain barrier, when injected intravenously. Additionally, it was found to stain neurofibrillary tangles characteristic of the disease.

The ability to confirm a diagnosis of Alzheimer's disease will mean that patients can receive earlier treatment.

—D Dye


June 21, 2000

Aspirin given early prevents recurrent ischemic strokes

The June issue of Stroke: Journal of the American Heart Association carried an article which demonstrated the benefit of giving aspirin to ischemic stroke patients immediately upon arrival at the hospital to prevent recurrent strokes. The weeks following a first stroke are considered high-risk for further strokes.

Lead study author ZhengMing Chen MD, headed a research group who analyzed the results of the Chinese Acute Stroke Trial and the International Stroke Trial, which studied a total of 40,000 patients. In both trials, half the patients were given medium dose aspirin within forty-eight hours of the stroke. The researchers discovered that aspirin given to stroke patients immediately after the stroke and for the following few weeks reduced the risk of another ischemic stroke during this period by one third.

Ischemic stroke is causes the majority of strokes by a blood clot blocking a blood vessel in the brain, whereas hemorrhagic stroke is caused by the rupture of a blood vessel within the brain, causing bleeding. A CT scan can determine which type of stroke has occurred. Although aspirin has been demonstrated to reduce second ischemic strokes in longterm studies, doctors have been concerned about giving it to patients immediately following the stroke because it might result in bleeding, caused by aspirin's anticlotting ability. But even if a CT scan is not available, the researchers felt that early treatment with aspirin should not be withheld. Seven hundred seventy-three patients in the study had entered the hospital with a hemorrhagic type stroke and were mistakenly given aspirin, but no significant was found between these patients and those who did not receive aspirin.

Dr. Chen commented, "We can be confident that there is no great hazard in giving aspirin immediately to patients who have been diagnosed with ischemic stroke. Of course, there may be some groups who should not get aspirin, but even the results in those who had bleeding strokes are reassuring . . . We must limit the number of hemorrhage patients who get aspirin, but it's also important to give the treatment to those who can immediately benefit."

—D Dye


June 19, 2000

Genetic factor found in cataract

The World Health Organization estimates that 45 million people suffer from blindness worldwide. Cataracts account for 50% of that blindness. Cataracts are a gradual opacity that occurs in the lens of the eye, obstructing vision. Free radical damage, sunlight exposure and smoking have all been shown to effect the development of cataracts. A study published in the June 15 issue of New England Journal of Medicine demonstrates the hereditary component of this condition.

The study examined 506 sets of British female twins, aged 50 to 79, for the presence of cataracts. Two hundred twenty-six of the pairs were identical twins while 240 were fraternal. Identical, or monozygotic twins, which are the result of the division of a single fertilized egg cell, share the same genes; while fraternal, or dizygotic twins share less genetic material because they are the result of the fertilization of two separate eggs . Analysis of the data demonstrated that genetics were responsible for almost half of the lens opacities observed. Age was determined to be responsible for 38 percent, and other factors combined caused 14 percent. Identical twins experienced a greater incidence of cataracts occurring in both twins than did fraternal twins, although fraternal twins also experienced a high rate of correlation. The authors of the study felt that the fraternal twins' high rate of correlation could be due to shared age or environmental factors.

The article noted, " . . . estimates of heritability are population-specific; our figure applies to a population of middle-aged-to-elderly British white women and may differ for other ethnic or racial groups or those with different environmental circumstances." However, this study is seen to be a breakthrough in understanding the etiology of cataract and could lead to research to uncover the genes involved.

—D Dye


June 16, 2000

Macular degeneration drug approved

The drug verteporfin was recently approved by the FDA to treat exudative age-related macular degeneration. Exudative, or "wet" macular degeneration occurs when abnormal blood vessels grow under the retina which leak fluid and blood into the macula, the yellow spot on the retina at the back of the eye. The degeneration of the macula causes blurred and distorted vision, and the scar tissue that is formed can cause a permanent loss of central vision. The approval of verteporfin is a first for macular degeneration related vision loss. It is being used with a nonthermal laser treatment called photodynamic therapy (PDT) at Penn State University. Verteporfin, which is a photosensitive dye, is infused by IV for ten minutes, allowing it to accumulate in the abnormal blood vessels in the macula, where it is then activated by a nonthermal laser, sealing the blood vessels. In one study, the benefits of the therapy continued for several years. David Quillin MD, assistant professor of ophthalmology at Penn State College of Medicine stated, "PDT offers an alternative over traditional laser therapy in that it selectively targets the abnormal blood vessels and spares the retina."

Macular degeneration is the leading cause of loss of vision for people over sixty-five. An angiogram of the area can determine if someone is a good candidate for photodynamic therapy if it indicates a specific pattern of macular damage.

—D Dye


June 14, 2000

Microwaves zap cancer cells

Massachusetts Institute of Technology recently announced the development of microwave energy treatments to heat and kill cancer cells. The therapy works on the simple fact that cancer cells contain higher percentages of water compared to normal cells, which renders them able to rapidly absorb microwave energy. Cancer cells can hold up to 80% of their weight in water whereas normal cells contain as little as 20% water. It has been known for some time that heat can be an effective therapy against cancer, but delivering the heat without burning the surrounding tissue was problematic. The new microwave technology is able to deliver deep, focused heat without damaging adjacent tissue.

The therapy was invented by Alan J. Fenn, senior staff member in the Advanced Electromagnetic Systems Group at MIT's Lincoln Laboratory who had originally been involved with missile detection technology. Dr Fenn stated, "About ten years ago we were working on radar anti-jamming technology to detect missiles from space-borne satellites. Then, with the end of the Cold War, the scientists were asked to explore alternative applications of the technology. I thought: why couldn't we use the microwave energy (that is key to the radar technology) on cancer cells?"

Robert Gardner MD and Hernan Vargas MD conducted a clinical trial on seven women scheduled for mastectomies. The women receiving the treatment experienced tumor shrinkage to half the original volumes after one week. Because of the study agreement, the mastectomies were carried out, which prevented the researchers from observing any further shrinkage. In future trials, a second microwave treatment could produce even better results. Dr Fenn stated, "Our goal is to destroy all visible and microscopic cancer cells and pre-cancerous cells in the breast."

Celsion Corporation holds a license agreement with MIT for the commercialization rights of this technology.

—D Dye


June 12, 2000

Gene Therapy for Rheumatoid Arthritis

Rheumatoid Arthritis is a disease characterized by chronic inflammation, thickened joint lining and destruction of cartilage. It is believed to be an autoimmune disease, although some current theories point to a possible viral or bacterial origin. The disease generally strikes young adults, and can lead to painful, deformed joints. At the annual meeting of the American Society of Gene Therapy held on the weekend of June 4-5, Targeted Genetics Corporation presented an abstract entitled, "Treatment of Experimental Arthritis Using Recombinant AAV-TNFR:Fc Vector Gene Therapy," describing its adeno-associated virus (AAV) vector technology to deliver the genes encoding TNFR:Fc, to treat the inflammation of rheumatoid arthritis. TNFR:Fc stands for tumor necrosis factor receptor-immunoglobulin Fc, a protein antagonist of tumor necrosis factor-alpha, which is involved in the inflammatory response. The researchers used a gene delivery system consisting of the injection of a genetically modified virus. The virus is able to deliver a copy of the gene encoding the protein into the genetic material of the targeted cells. The rats experienced significantly less inflammatory symptoms in areas receiving only a single injection. The researchers noted that blood levels of the TNFR:Fc protein did not rise significantly, leading them to observe that the effect appeared local rather than systemic.

Dr. Barrie Carter, Executive Vice President and Director, Research and Development of Targeted Genetics stated, "We believe that the safety profile and long-term expression properties of our AAV vectors make them a logical approach to developing a gene-based delivery system for this important therapeutic protein. Local delivery of AAV-TNFR:Fc to arthritic joints may allow patients to be dosed every few months while maintaining therapeutic levels of the protein between treatments. We are moving forward with the preclinical development of the human version of this construct."

H. Stewart Parker, President and Chief Executive Officer of Targeted Genetics, commented, "These data demonstrate that gene delivery may have a number of applications beyond the treatment of cancer or single-gene defects."

—D Dye


June 9, 2000

Supplemental folic acid better than diet in lowering homocysteine

Homocysteine is an amino acid formed in the body from another amino acid, methionine. High levels of homocysteine in the blood have been linked to cardiovascular disease. Vitamins such as folic acid and vitamin B6 can help to prevent elevated homocysteine. The June issue of the American Journal of Clinical Nutrition featured an article concerning a study in which folic acid from three different sources was given to sixty-five study participants in an attempt to determine which was the most effective in lowering plasma homocysteine. Patients were divided into four groups, and were placed on a standardized diet. A control group received the diet without a source of additional folic acid. One group received a folic acid (folate) supplement, another consumed folic acid enriched breakfast cereals and another was instructed to choose their diet from a list of folate-rich foods aided by recipes and suggested eating plans . Plasma homocysteine and serum folate were measured before the study, at six weeks and at twelve weeks. Six hundred micrograms was chosen for the amount of daily folic acid intake because there has been little or no homocysteine reduction associated with higher doses, and it is difficult to obtain more than that amount in the average diet.

Although the group that received folate from the diet consumed the greatest amount of the vitamin, their serum folate levels did not increase to the same extent. This group had the lowest measured decrease in plasma homocysteine (9%) which is not considered significant. The groups receiving folic acid from a tablet source and from fortified cereals experienced the greatest (21% and 24%, respectively) decrease in homocysteine. This study clearly demonstrates the benefit of adding supplemental folic acid to the diet, whether in the form of a vitamin tablet or a vitamin enriched food.

—D Dye


June 7, 2000

Islet cell transplant plus nonglucocorticoid immunosuppression successful in diabetes 1

The New England Journal of Medicine released an article today which documents the success of an immunosuppressive regimen combined with pancreatic islet cell transplants in diabetes type 1 patients. The article is scheduled for publication in the July 27 2000 issue of the journal, but is being released in advance because of its possible clinical implications.

The islets of Langerhans are small groups of endocrine cells scattered throughout the pancreas. Beta islet cells produce insulin, the hormone that regulates the amount of sugar in the blood. Diabetes type 1 is considered to be an autoimmune disease in which the immune system attacks and destroys the insulin-producing beta cells of the pancreas, making it necessary for the patient to self-administer insulin on a daily basis.

Since 1990, 267 recipients have received islet cell transplants. However, only 12.4 percent were able to control their blood sugar without supplemental insulin for more than a week and only 8.2 percent maintained insulin independence for a year. As in the case of other organ transplants, it is necessary to treat the transplant recipient with immunosuppressive drugs to prevent rejection from occurring. Most of the patients who received islet cell transplants were given a combination of of drugs that included glucocorticoids, which can induce insulin resistance or damage beta cells. In the current study, islet cell transplant recipients were treated with an immunosuppressive regimen that was free of glucocorticoids. The seven diabetes type 1 patients in the study quickly achieved insulin independence, which was sustained during follow up. Although six of the patients received additional islet cell infusions, none have experienced rejection and all have remained free of insulin dependence.

—D Dye


June 2, 2000

Lupus discovery announced

Lupus is an autoimmune disease in which the body attacks its own tissues, causing inflammatory symptoms such as arthritis, fatigue and fever. The most common form of lupus is systemic lupus erythematosus. The Lupus Foundation of America estimates that up to two million Americans have systemic lupus erythematosus. Researchers in laboratories in Essen and Bochum, Germany discovered that a deficiency of the enzyme DNase1 could be a cause. DNase1 eliminates ``garbage DNA'' and other cellular leftovers by breaking them up. Researchers had speculated that a mutation interfering with cellular waste removal could be the culprit in lupus. In a study reported in Nature Genetics, researchers tested the hypothesis by breeding mice with the gene encoding DNase1 switched off. The majority of the mice developed symptoms of lupus after six to eight months. The researchers believe that the immune reactions of mice are very similar to humans'. Mark J Walport of London's Imperial College commented, ``These mice add strong support to the hypothesis that impairment of the normal disposal of cellular debris predisposes the development' of lupus."

DNase1 is often found to be low in human lupus patients. Because there are other factors involved in the development of lupus, the researchers don't know whether DNase1 supplementation will help patients suffering from the disease. A synthetic version of the enzyme is already being manufactured for other purposes.

—D Dye


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