Feb. 05/2003

The Case for Adult Stem Cell Research

by Wolfgang Lillge, M.D

(et kort utdrag/ a short excerpt)

... In 2001 a team of doctors at the Duesseldorf University Clinic carried out a treatment of very far-reaching consequences. For the first time, they treated a cardiac infarct patient with stem cells from his own body. The cardiologist, Prof. Bodo Eckehard Strauer, is sure that the stem cells from the patient’s bone marrow, after injection into the infarct zone, autonomously converted to heart muscle. The functioning of the severely damaged heart clearly improved within a few weeks.

Four days after the infarction, the doctors took bone marrow from the patient’s pelvis using local anesthesia. The stem cells in the marrow were concentrated outside of the body and implanted in the infarct area the next day with a special technique via a coronary artery. However, the doctors could not yet take cardiac tissue to prove definitively that the implanted blood stem cells had converted to heart muscle cells. But, according to Strauer, there is no other way to explain the marked improvement in the patient’s condition. After this first successful operation, six more patients have already been treated with their own stem cells, with similarly positive results.

There are also reports of successful treatments with adult stem cells in cases of Crohn’s disease (a chronic infection of the gut), thalassemia (a blood disease), and a rare skin disease. And–despite the fact that basic research with adult stem cells is in its earliest beginnings and is in no way being promoted with urgency–there have been a growing number of reports lately of experiments with animals, from which it emerges that adult stem cells can successfully transform themselves into differentiated cells of organs of many kinds.

In contrast, reports of successful conversions of embryonic stem cells are very infrequent and cautious. Thus, we find in Science of Dec. 1, 2000 (Vol. 290, pp. 1672-1674): "In contrast, the human embryonic stem cells and fetal germ cells that made headlines in November 1998 because they can, in theory, develop into any cell type have so far produced relatively modest results. Only a few papers and meeting reports have emerged from the handful of labs that work with human pluripotent cells. . . . The work suggests that it will not be simple to produce the pure populations of certain cell types that would be required for safe and reliable cell therapies. . . ."...

Relaterte linker / Related links:

1. Bone Marrow Generates New Neurons in Human Brains 
   A new study strongly suggests that some cells from bone marrow can enter the human brain and generate new neurons and other types of brain cells. 
2. Why cloning if you have bone marrow?
3. DIRECTED DIFFERENTIATION OF EMBRYONIC STEM CELLS INTO MOTOR NEURONS
4. Neuronal replacement from endogenous precursors in the adult brain after stroke.
5. Adult Stem Cells Successful In Treating Crohn's Disease
   The whole process, including recovery, takes three weeks

Journal of the American Medical Association

Stem Cells Step Closer to the Clinic
Paralysis Partially Reversed in Rats With ALS-like Disease 

In the most dramatic demonstration of stem cells' potential to date, this rat and a dozen others partially recovered from paralysis after injections of laboratory-sprouted, intermediate-stage stem cells. Grown from a patch of fetal tissue, these human cells settled into the rat's spinal column and_somehow_brought life to dead feet. ...mer/more...

Relaterte linker / Related links

Cell Transplantation
An Introduction to Brain Cell Transplantation

http://www.reneuron.com/

A number of conditions lead to death of brain cells. Cells may die gradually, as in neurodegenerative conditions such as Parkinson's disease, Huntington's disease and Alzheimer's disease, or abruptly in conditions such as stroke or cerebral palsy when the supply of oxygen to the brain is inadequate.

Although there are billions of cells in the brain the selective loss of even half a million can give rise to serious problems. It seems that the brain has a relatively limited capacity to repair and cannot regenerate the lost cells or restoring the damaged circuits ('re-wiring').

Treatment alternatives for these diseases are limited and none are completely satisfactory. Alternative treatments are being developed to try and prevent brain cell death, to stimulate the growth of existing stem cells in the damaged brain, or, by novel cell-based therapies, to replace dead or diseased cells with cell transplants. ...mer/more...

© Copyrighted material above used with permission of ReNeuron

12. Feb. 2002

nerveregenereringsbehandling
nerve regenerative treatment

BOSTON LIFE SCIENCES' "INOSINE" RESTORES MOTOR FUNCTION AFTER EXPERIMENTAL STROKE

First successful demonstration of nerve regenerative treatment resulting in functional improvement presented at meeting of American Academy of Neurosurgery

December 17, 2001-Boston, MA-Boston Life Sciences (NASDAQ: BLSI) announced that the Company's nerve regeneration product Inosine, successfully restored fine motor function in rats following induction of a severe stroke involving the motor cortex. Preliminary results from these experimental studies were presented by Dr. Peng Chen of Children's Hospital and Harvard Medical School, Boston, at the recent meeting of the American Academy of Neurosurgery. Dr. Chen received the "Academy Award" for this work, which is given to a Neurosurgical Resident presenting what is considered the most significant scientific work at the Academy's Annual Meeting. The complete results of the studies have been submitted for publication in one of the pre-eminent scientific publications in the world.

BLSI is developing Inosine for the treatment of stroke and other CNS disorders, and has supported ongoing basic research of Inosine and other CNS growth factors at Children's Hospital for a number of years. BLSI owns the exclusive license to commercialize Inosine for a variety of CNS indications including stroke.

"We are proud of Dr. Chen and his team for garnering such recognition for this outstanding scientific achievement," stated Marc Lanser, MD, Chief Scientific Officer of BLSI. "This research is at the forefront of nerve regeneration therapy, demonstrating functional recovery based on this approach. We are looking forward to being the first Company to enter into clinical testing utilizing this nerve regenerative approach to stroke treatment. We anticipate filing our Investigational New Drug (IND) application for this indication in the first half of 2002," added Dr. Lanser.

BLSI is developing novel diagnostics and therapeutics for Parkinson's Disease (PD) and Attention Deficit Hyperactivity Disorder (ADHD) as well as treatments for cancer, autoimmune disease, and central nervous system disorders. BLSI's products in development include: ALTROPANETM and FLUORATECTM radioimaging agents for the diagnosis of PD and ADHD; Troponin I, a naturally-occurring anti-angiogenesis factor for the treatment of solid tumors; AF-1 and Inosine, nerve growth factors for the treatment of acute and chronic CNS disorders; novel therapies for the treatment of PD and ADHD; and transcription factors that may control the expression of molecules associated with autoimmune disease and allergies.

Statements made in this press release other than statements of historical fact represent forward-looking statements. Such statements include, without limitation, statements regarding expectations or beliefs as to future results or events, such as the expected timing and results of clinical trials, discussions with regulatory agencies, schedules of IND, NDA and all other regulatory submissions, the timing of product introductions, the possible approval of products, and the market size and possible advantages of the Company's products. All such forward-looking statements involve substantial risks and uncertainties, and actual results may vary materially from these statements. Factors that may affect future results include: the availability and adequacy of financial resources, the ability to obtain intellectual property protection, delays in the regulatory or development processes, results of scientific data from clinical trials, the outcome of discussions with potential partners, regulatory decisions, market acceptance of the Company's products, and other possible risks and uncertainties that have been noted in reports filed by the Company with the Securities and Exchange Commission, including the Company's Annual Report on Form 10-K.

Feb. 12.02

ScienceDaily:

Influensavaksine kan bidra til å forhindre slag

Source:American Heart Association (http://www.americanheart.org/)

Feb. 12.02

ScienceDaily:

Rutgers Universitet utvikler Virtual Reality terapi for opptrening av håndbevegelser hos kroniske slagpasienter

Source: Rutgers, The State University Of New Jersey (http://www.rutgers.edu/)

ScienceDaily:

Transplanterte "voksne" stamceller tilbakefører funksjoner etter slag, i dyreforsøk.

University Of Minnesota (http://www.umn.edu/)

The Journal of Neuroscience, July 15, 2001, 21(14):5272-5280

Enriched Rehabilitative Training Promotes Improved Forelimb Motor Function and Enhanced Dendritic Growth after Focal Ischemic Injury

Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1B 3V6

Chronic impairment of forelimb and digit movement is a common problem after stroke that is resistant to therapy. Previous studies have demonstrated that enrichment improves behavioral outcome after focal ischemia; however, postischemic enrichment alone is not capable of enhancing fine digit and forelimb function. Therefore, we combined environmental enrichment with daily skilled-reach training to assess the effect of intensive task-specific rehabilitation on long-term functional outcome. Rats were subjected to either endothelin-1-induced focal ischemia or sham surgery and subsequently designated to enriched-rehabilitation or standard-housing treatment groups starting 15 d after ischemia. Functional assessment of the affected forelimb at 4 and 9 weeks after treatment revealed that ischemic plus enrichment (IE) animals had improved ~30% on the staircase-reaching task and were indistinguishable from sham animals for both latency and foot faults in a beam-traversing task. In contrast, ischemic plus standard (IS) animals remained significantly impaired on both tasks. Interestingly, both ischemic groups (IE and IS) relied on the nonaffected forelimb during upright weight-bearing movements, a pattern that persisted for the duration of the experiment. Dendritic arborization of layer V pyramidal cells within the undamaged motor cortex was examined using a Golgi-Cox procedure. IE animals showed enhanced dendritic complexity and length compared with both IS and sham groups. These results suggest that enrichment combined with task-specific rehabilitative therapy is capable of augmenting intrinsic neuronal plasticity within noninjured, functionally connected brain regions, as well as promoting enhanced functional outcome.

Doctor's Guide 

DG DISPATCH - STROKE: Zanaflex Reduces Spasticity Resulting From Stroke

By Cameron Johnston
Special to DG News

NEW ORLEANS, LA -- February 14, 2000 -- Zanaflex (tizanidine hydrochloride), which is currently used in the treatment of multiple sclerosis, has been found useful in treating patients who develop spastic limbs as a result of an acute cerebral infarct.

The findings from a small study were presented at the American Stroke Association's 25th International Stroke Conference, being held Feb. 10-12 in New Orleans, LA. The American Stroke Association is a division of the American Heart Association.

Approximately one-third of all stroke patients experience some degree of spasticity, invariably on one side rather than on both sides of the body, and frequently in an arm more so than in a leg, explained Dr. David Gelber, an associate professor of neurology at the Southern Illinois University School of Medicine, in Springfield.

Forty-seven patients who had had strokes were treated with Zanaflex by Dr. Gelber and colleagues, at a dose beginning at 2 mg/day, which was then titrated upward by an additional 2 mg/day until the patient reached a final daily dose of 20 mg/day at the end of a 16-week period. Seventeen of the patients reached doses to a maximum of 36 mg/day.

The degree of spasticity the patients experienced was graded on a Modified Ashworh Scale, which rates the spasticity subjectively: 0 = no stiffness, and 4 = total rigidity in the affected limb. Four muscles in each arm were evaluated, so in the most extreme cases, a patient could rate 16 points per limb.

In this study, the mean change in Ashworth scores for all patients was 2.80 after 16 weeks of therapy.

Sixty-four per cent of the patients experienced at least some improvement, while 31 percent experienced an improvement of at least four points. The effects of the drug are short-lived; two weeks after discontinuing the drug, the mean score change had fallen to 1.59.

While Zanaflex has been used for some time in patients with multiple sclerosis, Dr. Gelber said what is noteworthy here, is that the average age of MS patients who use the drug is between 30 to 35, whereas the average age of the patients in this study was just over 60.

Dr. Gelber added that there is no reason why some patients could not receive the drug within a week of having a stroke although, in this study, the mean time since the stroke was more than 29 months for each patient. This was done, he said, to ensure that the patients were past the point of spontaneous improvement. Also, he said, by the 29-month mark, the patients would probably have achieved whatever improvement from physiotherapy and other forms of rehabilitation that they were likely to see.

During the course of the study, the patients were not allowed to take any other form of medication that might affect their spasticity or that might potentiate the effects of  Zanaflex

Zanaflex.Related Link: Zanaflex (tizanidine hydrochloride).

(Norsk merkenavn på Zanaflex er: "Sirdalud")

Det ryktes at Zanaflexprodusenten, (Novartis) har gitt opp å få Zanaflex godkjent for bruk i Norge, mens det i Danmark visstnok er både godkjent og benyttet

Mine kommentarer Trond Ruud

Stamcellenevroner: Fra dyreforsøk til slagbehandling

Stem Cell Neurons from Animal Trials to human Stroke Treatment

BBC Science/Nature 

Friday, 20 December, 2002, 09:00 GMT

 30. mars/March 2002

Earlier good news about "adult" stem cells may have been premature.

Tidligere, gode nyheter om forskning på bruk av "voksne" stamceller kan ha vært for optimistiske:

Adult stem cell promise may be deceptive

19:00 13 March 20

NewScientist.com news service

Hopes that research into embryonic stem cells could be abandoned in favour of adult stem cells may be premature. Those claiming adult stem cells are just as versatile as embryonic ones may have been misled by an experimental artifact.

Two groups led by Austin Smith of the University of Edinburgh and Edward Scott of the University of Florida have discovered that adult stem cells that appear capable of forming a range of tissue types may not really be doing it by themselves. Instead, they might be fusing with other cells to form abnormal hybrids that could be mistaken for pristine new tissues.

"We are not saying that those findings are wrong," says Naohiro Terada of the Florida team. But researchers should not conclude that their cells have changed developmental paths without checking if fusion is the cause, he says.

There is strong opposition to embryonic stem cell (ESC) research in many countries because it involves destroying early human embryos. Critics argue that adult stem cells show so much promise that there is no need to mess around with embryos.

Now, however, adult stem cell researchers will have a much harder time convincing other scientists that this promise is real. "I agree that based on those data it's incumbent upon us to prove whether or not fusion is responsible for [what] we have called 'plasticity'," says Diane Krause of Yale University.

Relaterte linker/Related links:

21.Juni 2002

"Six months after therapy the patients brains were remapped and the changes appeared to be permanent..."

"Seks måneder etter terapien ble pasientenes hjerner kartlagt pånytt og forandringene så ut til å være permanente..."

Slagterapi gjennom hjernetrening -
Stroke therapy by jogging the brain

Ikke en dagsfersk nyhet dette, men allikevel en meget interessant terapi, pga. metodens tilforlatelige enkelhet.

Not excactly the latest news this, but very interesting anyway because of the logical approach and simplicity of the therapy

Noen hovedpunkter på norsk (some highlights in Norwegian, see english text farther below) 
Etter et slag, dør enkelte celler, men langt flere celler hensettes i en sjokktilstand, sa Dr. Taub. Noen ganger restitueres disse cellene spontant og pasienten blir bedre. Men mer vanlig er det at cellene som er knyttet sammen i nettverkene, som kontrollerer bevegelse av lemmene, forblir svimeslåtte, i en slags permanent passivitet. Hver gang en pasient forsøker å bruke sin dårlige arm og mislykkes, sa Dr. Taub, så vil det mislykkede forsøket forsterke passivitetstilstanden. Evnen til å bevege armen blir dermed suksessivt mer undertrykt i en slags tillært hjelpeløshet

Evnen til bevegelse har ikke forsvunnet, sa han, men pasienten har gitt opp å forsøke. Og ved å kompansere med den "friske" siden forsterkes denne ytterligere. Og dette forholdet gjenspeiles i hvordan hjernen reorganiserer seg etter slaget. F.eks. krymper cellenettverkene som styrer armbevegelsene på den rammede siden med 70%, mens cellenettverkene på den uskadde siden vokser, men ikke så mye som den andre siden reduseres.For å se om de kunne få de skadede cellenettverkene til å vokse, introduserte Dr. Taub og hans kolleger noe de kaller hemningsindusert bevegelsesterapi. Det innebærer at pasientens friske arm tjores fast, slik at den dårlige armen ble tvunget til å bevege seg. Dette, antok de, ville tvinge hjernen til å gi opp sin tillærte hjelpesløshet.

Terapien fungerte, sa Dr Taub. Omtrent 250 pasienter har blitt behandlet ved forskjellige forskningsanstalter rundt om i landet, med utmerkede resultater, sa han
Mange nye studier på terapien holder nå på å starte opp, sa Dr. Taub. I Dr. Taubs egen studiegruppe deltok 13 menn og kvinner, som hadde hatt en arm lammet av slag i mellom 6 måneder og 17 år.
Terapien fungerer bare, sa forskerne (ved Duke University Medical Center in Durham, N.C.), dersom den benyttes seks timer om dagen i minst to uker. Når tilsvarende konsentrert terapi gis bare to eller tre ganger om uken, sa de, blir ikke hjernen tilstrekkelig stimulert til å reorganisere seg selv. 
Den fulle teksten finnes i den engelske artikkelen fra New York Times nedenfor (Study Offers Hope for Use of Limbs Disabled by Stroke)

-oOo-

  - Science

(June 2, 2000)

Study Offers Hope for Use of Limbs Disabled by Stroke

By SANDRA BLAKESLEE

Using a new kind of stroke rehabilitation therapy, scientists have shown for the first time that the brain can be coaxed into reorganizing its circuitry so that people can regain nearly full use of their paralyzed limbs in just two to three weeks, even if the stroke happened years ago.

The rehabilitation involves immobilizing a good arm or leg so that the patient is forced to use the paralyzed arm or leg for familiar tasks.

By intensively using the paralyzed limb, people can literally rewire parts of their brains, researchers said, and overcome a kind of learned helplessness that prevented their limbs from moving. Moreover, the technique works for patients who had their strokes even decades ago and have had limited use of their limbs ever since.

The findings, by scientists at the University of Alabama and the Freidrich Schiller University of Jena in Germany, involved only the arms of 13 patients, but the researchers say similar methods will also work for paralyzed legs.

Several studies are under way in an effort to confirm the findings and test the theory that paralyzed legs can also be restored.

But the results involving the 13 patients, reported today in the June 2000 issue of Stroke: Journal of the American Heart Association, join a growing body of evidence that the adult brain is capable of reorganizing itself after injury. The newly reported study made maps of an area of the brain in the 13 chronic stroke patients before and after the intensive therapy, called constraint-induced-movement therapy. Researchers found that the area, which was responsible for arm movements on the injured side of the brain, had nearly doubled in size after the therapy.

The therapy only works, researchers said, if it is given six hours a day for at least two weeks.

When similarly intense therapy is offered only two or three days a week, they said, the brain is not sufficiently stimulated to reorganize itself.

But Dr. Larry Goldstein, a professor at Duke University Medical Center in Durham, N.C., and an expert on stroke, said it was too soon to say whether the new approach would find widespread use. While the study is interesting, Dr. Goldstein said, it has some "big limitations," in that it is based on a very small number of patients and they were not compared with a control group.

"Is it promising?" he asked.

"Yes. Is it proven? No."

Four million people now live with the effects of stroke, two-thirds of whom are moderately or severely impaired.

The fact that an adult brain can rewire itself after injury has been shown in animals for over 50 years, said Dr. Edward Taub, a neurologist at the University of Alabama in Birmingham and an author of the study. This led researchers to wonder if ways could be found to promote such rewiring in human stroke patients.

After a stroke, some cells die but many more are left in a state of shock, Dr. Taub said.

Sometimes these stunned cells recover spontaneously and the patient gets better. But more often, the cells, which might make up networks that control limb movements, remain stunned, in a state of permanent inhibition. Every time a patient tries to use his bad arm and fails, Dr. Taub said, the failure is reinforced. The ability to move gets suppressed, in a kind of learned helplessness.

The ability to move has not been abolished, he said, but the patient has given up trying.

Meanwhile, Dr. Taub said, patients start to depend on their good arms to carry out everyday tasks and those movements are similarly reinforced.

This state of affairs is reflected in brain organization.

For example, cellular networks responsible for arm movements on the injured side of the brain will often shrink by 70 percent whereas the same networks on the uninjured side will expand in size, though not as much.

To see if injured networks can be made to expand, Dr. Taub and his colleagues came up with what they called constraint-induced-movement therapy. It involves strapping down a patient's good arm and forcing the bad arm to do all the work. This, they reasoned, should force the brain to give up its learned helplessness.

The therapy worked, Dr. Taub said. About 250 patients have been treated in several research laboratories nationwide with excellent results, he said.

The National Institute of Health is about to begin multicenter clinical trials of the therapy.

Many other studies of the therapy are now under way, Dr. Taub said.

The 13 men and women in Dr. Taub's study had an arm paralyzed from strokes suffered 6 months to 17 years ago.

Before the therapy, these patients came into the laboratory where their brains were mapped with a special magnetic device that detects the area of the brain where various muscles are represented. In this study, the researchers made maps of the small muscle that connects the thumb to the rest of the hand and used it as a surrogate for the paralyzed arm.

If the representation of this muscle could be made to expand in the brain, Dr. Taub said, all the stimulated arm muscles should also expand. Before therapy, the thumb muscle of paralyzed patients showed activity at only 12 positions on the magnetic map, Dr. Taub said. ...mer/more....

Relaterte linker / Related links:

1. Pushing Injured Brains And Spinal Cords To New Paths

2. Helping the brain fix its own wiring

3. Somatosensory Deafferentation

4. Hard Work Pays Off
   

27.Nov.2003

According to Ehlers, the findings by him and his colleagues could aid understanding of how brain tissue is damaged during stroke, and altered in pathological states of addiction or following injury.

'Reset Switch' for Brain Cells Discovered

..mer/more...