Re: Drug treatment improves learning in mice with ...

[Guest guest]

Everyone keeps talking about ginko. I am going to research tonight after the kids are in bed. Do you have to worry about interactions with other medications? Sara is already taking Nutrivene D.....SO many questions? Does anyone have some information to offer so when I go searching I go in the right direction? Thank you! MarcyAOL now offers free email to everyone. Find out more about what's free from AOL at AOL.com.

[Guest guest]

Marcy,

We give my brother Ginkgo. He also takes Nutrivene-D, Tart Cherry, Blueberry w/ Pomegranate, zinc, DHA, and Turmeric. I'll paste some info into this email and some info attached to this email.

------

Ginkgo biloba in Down Syndrome. Phytomedicine 11 (2004) 469. Reprintpermission granted by the principal author and Huber, RightsManager Journals, Elsevier GmbH, E-mail: m.huberelsevier. © 2004Elsevier GmbH. All rights reserved. www.elsevier.de/phymed.A cholinergic therapy based on the use of Donepezil has reported goodresults in four adults with Down Syndrome (DS) (Kishnani et al.,1999). Kishnani and colleagues took into consideration similaritiesbetween the neurobiology of Alzheimer's Disease and of DS.Ginkgo biloba (standardized extract EGb 761) has shown the sameefficacy as Donepezil and other cholinesterase inhibitors in thetreatment of dementia (Wettstein, 2000). Ginkgo standardized extractalso seems to have a direct effect on the cholinergic system (DeFeudisand Drieu, 2000). In individuals with DS, therapy with standardisedGinkgo biloba extract could be an effective aid to cognitive andsocial skills intervention.We examined two young patients with trisomy 21 (diagnosed bycytogenetic analysis) to verify this hypothesis. They were notaffected by cardiac or other malformations nor had they othersignificant medical conditions. A psychiatric assessment was performedusing a semi-structured psychiatric interview for children andadolescents (K-SADS PL 1.0). It was necessary to exclude any bias dueto change in psychiatric conditions during therapy. Patients did notshow significant psychopathology. Mental retardation was diagnosedthrough the use of the age-appropriate Wechsler Scale, and an Italiancomplete version of the Vineland Adaptive Behaviour Scale.Medication was given during the summer holidays, when school,rehabilitation and educational training are suspended. In both casesinformed consent was obtained from parents.The first case involved a boy 10 years 11 months old with an I.Q. of40 and a Vineland scale total score of 455. He received standardisedextract of Ginkgo biloba (GK 501, Pharmaton), at a dose of 80 mg everymorning for 11 weeks.After this period, a Vineland retest showed an improvement in totalscore: 497. This child showed a major improvement in personal autonomywith an increase of 16: he learned to put on his shoes and to tie hisshoelaces. In social behaviour, an improvement of 8 points wasrecorded: he began to make friends spontaneously.The second patient was aged 17 years and 8 months, and had an I.Q. of44; the Vineland scale total score was 721. The patient receivedGinkgo biloba GK 501, at a dose of 120mg every morning for 13 weeks.Vineland retest showed an improvement, with a total score of 758. Anincrease of 8 points in writing scores was recorded; the boy beganmemorising and writing more than 20 words and writing little notesspontaneously. The patient showed an improvement in imitation score (8points). He had a better control of impulsiveness and anger.None of the two patients had side effects during therapy.These results seem to indicate that, in DS patients, GK 501 therapycould be effective on improving social and academic skills. Usually,DS people do not show spontaneous improvement in the space of 3months. A double blind controlled trial is of course needed todemonstrate the efficacy, safety and effectiveness of Ginkgo bilobaextract in DS.ReferencesDeFeudis, F.V., Drieu, K., 2000. Ginkgo biloba extract (EGb 761) andCNS functions: basic studies and clinical applications. Curr. DrugTargets 1 (1), 25-58.Kishnani, P.S., Sullivan, J.A., Walter, B.K., Spiridigliozzi, G.A.,Doraiswamy, P.M., Krishnan, K.R., 1999. Cholinergic therapy for Down'sSyndrome. Lancet 2, 353 (9158), 1064-1065.Wettstein, A., 2000. Cholinesterase inhibitors and Ginkgo extracts-arethey comparable in the treatment of dementia? Comparison of publishedplacebo-controlled efficacy studies of at least six months' duration.Phytomedicine 6 (6), 393-401. http://www.altonweb.com/cs/downsyndrome/index.htm?page=feb05.html

----------

http://www.jneuroinflammation.com/content/1/1/4

-----------

"Ginkgo works on the glutamate receptor. That receptor in the area of the hippocampus acts like a gate. The hippocampus is the area of the brain used for short term memory storage for up to 90 days though some studies show it to be up to a year. The gate is held open for a certain amount of time allowing short term memory in. In DS this receptor like most others is decreased so the gate opening is short and infrequent limiting short term memory acquisition. Ginkgo (made up of two terpine hydrides named ginkgolides and bilobides) works mildly to increase the gate time. Other, more effective, medications are in the pipeline as they are ideal Alzheimer drugs and therefore good for DS but these are not getting into production in a timely manner. Ginkgo is easily available with few if any side effects so it is used.

Dr. Leichtman"

------------

http://www.mercola.com/2006/dec/9/more-evidence-ginkgo-biloba-works-just-as-well-as-dementia-drugs.htm

http://www.drugdigest.org/DD/DVH/HerbsWho/0,3923,4017|Ginkgo,00.html

www.curingdownsyndrome.com

---------

http://www.altonweb.com/cs/downsyndrome/index.htm?page=feb07.html

9th World Down Syndrome Congress

Exploring the Neurobiological Basis for Cognitive Problems in Down Syndrome. Mobley, M.D., Ph.D. Stanford University School of Medicine. 9th World Down Syndrome Congress Presentation. Vancouver, B.C., Canada.

Down syndrome (DS) is caused by an extra copy (i.e., trisomy) of chromosome 21. Cognitive problems are experienced by people with DS throughout the lifespan. Children with DS show varying degrees of cognitive slowing. All people over the age of 40 years with DS show the neuropathology of Alzheimer's disease (AD) and many people suffer further cognitive decline (i.e., dementia) in their 60s and beyond. Until very recently, scientists saw the problems posed by an extra copy of an entire chromosome as too complex to analyze. Moreover, it was believed that since DS problems arose during development, little could be done to reverse the damage. Fortunately, recent scientific advances have brought new tools and concepts to the biology of DS. Using modern genetic technologies and the results of the human genome project, it is now possible to define the gene(s) responsible for any atypical feature in people with DS. Moreover, advances in neuroscience have made it feasible to discover these changes, elucidate their mechanism, and develop new pharmacological therapies. The insights developed through this research not only will help children with DS, but also will have a direct impact on new treatments for Alzheimer's disease. One cause of cognitive problems in DS evident from structural and functional studies is that the hippocampus-a brain region whose function is critical for brain regions. Also, we know that basal forebrain cholinergic neurons (BFCNs), which innervate the hippocampus and are critically important for learning and memory, are abnormal in both children and adults. It is therefore believed that BFCN dysfunction and degeneration contribute to developmental and age-related problems in cognition in both Down syndrome and Alzheimer's disease. But as yet there is no insight into how this is caused or how to ameliorate dysfunction of BFCNs and thereby enhance cognition.

The hypothesis that guides our work is that each cognitive abnormality in DS is due directly or indirectly to increased expression of a specific gene(s) on chromosome 21. By discovering the responsible gene(s) it may be possible to prevent or rescue the defect. Our studies place a particular emphasis on hippocampal circuits that mediate learning and memory. We examine mouse models of DS and define changes that recapitulate those seen in DS. The Ts65Dn mouse model has a third copy of a portion of mouse chromosome 16 which is very similar to human chromosome 21 in that it contains an extra copy of about 140 homologous genes. Importantly, these mice show abnormalities in cognitive tasks mediated by hippocampus, including defects in spatial learning and memory.

Studies in young mice have shown abnormalities in the structure and function of synapses that closely resemble those in people with DS. Our findings point to an increase in inhibitory neurotransmission that could compromise circuit function and impair learning and memory. We will discuss the findings and indicate how ongoing studies are attempting to understand and overcome the abnormalities detected. BFCNs are responsible for the cholinergic innervation of the hippocampus. Cholinergic innervation of the hippocampus is known to be important for short-term spatial learning and memory. Atrophy and loss of BFCNs are consistent features in people with DS and AD, a change believed to contribute significantly to the resulting cognitive difficulties. The Ts65Dn mouse exhibits the abnormality, showing progressive age-related atrophy and loss of BFCNs within the hippocampus. We have explored the cause for BFCN degeneration, gathering evidence that failed signaling of nerve growth factor (NGF) is important. NGF, which is produced in the hippocampus, is critical for the normal development of BFCNs and for maintenance of their integrity and innervation of the hippocampus. We discovered that in DS mice there is marked disruption of NGF retrograde transport to about 10% of normal levels. To ask whether or not this was significant, we bypassed the defect by administering NGF directly to the cell bodies of BFCNs. This resulted in complete reversal of the atrophy and apparent loss of BFCNs.

Slides courtesy of Mobley, M.D., Ph.D.

These data strongly supported the view that in the absence of sufficient retrograde transport of NGF within signaling endosomes, BFCNs become shrunken and dysfunctional, but do not die. We found that a region containing about 40 genes was needed for the defect in NGF transport and BFCN degeneration. This region included the gene for amyloid precursor protein (App). To test for what role App might play, Ts65Dn mice were mated with mice heterozygous for deletion of App. The offspring included TsSDn mice with either 3 or 2 copies of APP. The mice with two copies of App showed no defect in BFCN size. Importantly, deleting the third copy of App also markedly increased NGF transport. These data are evidence for an important role for the third copy of App. This suggests the pathogenetic sequence: Increased APP Expression ¢ª Decreased NGF Transport ¢ª Loss of BFCNs ¢ª Abnormal Cognition. Thus, even in the context of a complex genetic lesion, overexpression of but one gene can produce important changes. We are now exploring the mechanism for disruption in NGF transport and are beginning studies to show whether or not reducing APP protein levels can prevent or reverse the deficits in transport and BFCNs.

Exploring the Neurobiological Basis for Cognitive Problems in Down Syndrome. Commentary by Dr. Cody.

I would like to extend my thanks to Dr. Mobley's Stanford University Down Syndrome Research team. They are moving research into uncharted territory and uncovering positive discoveries for more treatment options. (Hippocampal Long-Term Potentiation Suppressed by Increased Inhibition in the Ts65Dn Mouse, a Genetic Model of Down Syndrome. J Neurosci. 2004 Sep 15; 24(37):8153-60)

This is the most exciting time in the history of DS research with the advent of a genetically engineered DS mouse, this means to add or subtract a gene or genes to/from that mouse.

Produce mice that have DS. That means mice with an extra copy of the smallest chromosome, which exhibit DS phenotypes. Produce second and third generation DS mice in where extra segments of the extra chromosome are deleted. Then determine if the absence of that segment reduces or eliminates the DS phenotypes/abnormalities.

With these technical advances, delivering a treatment is possible.

Stanford first looked at the brain region critical for learning and memory. They examined structure, as well as, function. It turns out they go hand in hand.

Two problems emerged. The shape of the end of the nerve is too big and the nerves are not being used. Like muscles, without use, the nerves become weak and do not maintain their proper shape.

This may sound impossible to treat but the scientists figured out why the nerves were not working. The GABA receptor is turned on all the time, shutting down the rest of the nervous system. Stanford is now working on developing a pharmaceutical product that will turn GABA down to the right level. In the meantime, the herb Ginkgo Biloba, which has been used for years to increase memory in the elderly, is a mild GABA antagonist, i.e., turns GABA down. (Bilobalide, a sesquiterpene trilactone from Ginkgo biloba, is an antagonist at recombinant ¦Á1¦Â2¦Ã2L GABA(A) receptors. Eur J Pharmacol. 2003 Mar 7;464(1):1-8)

The University of Sydney has been studying the GABA receptor in detail and concluded that Ginkgo Biloba is a safe, effective GABA antagonist. (Ginkgolides, diterpene trilactones of Ginkgo biloba, as antagonists at recombinant ¦Á1¦Â2¦Ã2L GABA(A) receptors. Eur J Pharmacol. 2004 Jun 28; 494(2-3):131-8)

The next step being studied is why is there a lack of maintenance of the nerves? Nerves must be maintained with chemicals called growth factors. These growth factors (little packets of nerve nutrition) are transported down a nerve 'highway' if you will. In the DS mouse model, the scientists discovered the highway was shut down and no growth factors made it to the nerves. This leaves the nerves vulnerable and unable to survive.

The good news is that when the highway was bypassed and growth factors were placed directly on the nerves; the nerves revived as if they had been sleeping, not dead. Stanford used the DS mouse to narrow down the responsible gene(s). The likely candidate is a gene called APP. This acronym may be familiar because it is being studied extensively in Alzheimer's disease.

Treatment options include turning down the expression of APP or increasing availability of growth factors.

Dr. Mobley's presentation truly gives us insight into new avenues of treatment. At one time, Down syndrome was considered too complex to resolve but as with other medical mysteries, it is being unraveled by modern day science.

Dr. Cody, University of Texas Dental Branch 1992; Bachelors Degree in Biology from the University of Texas in Austin, 1988. Dr. Cody has a private practice in the Houston area that specializes in children with disabilities. She served on the Down Syndrome Research board 2004-5, spearheading the Adopt a Mouse fundraiser and is an advisor to the Down Syndrome Association of Houston. See: http://www.curingdownsyndrome.com.

Qadoshyah

*Got Down Syndrome?

www.gotdownsyndrome.net

From: Down Syndrome Treatment [mailto:Down Syndrome Treatment ] On Behalf Of rdavis900@...Sent: Monday, February 26, 2007 4:19 PMDown Syndrome Treatment Subject: Re: Drug treatment improves learning in mice with ...

Everyone keeps talking about ginko. I am going to research tonight after the kids are in bed. Do you have to worry about interactions with other medications? Sara is already taking Nutrivene D.....SO many questions? Does anyone have some information to offer so when I go searching I go in the right direction? Thank you! Marcy

AOL now offers free email to everyone. Find out more about what's free from AOL at AOL.com.

[Guest guest]

Marcy,

We give my brother Ginkgo. He also takes Nutrivene-D, Tart Cherry, Blueberry w/ Pomegranate, zinc, DHA, and Turmeric. I'll paste some info into this email and some info attached to this email.

------

Ginkgo biloba in Down Syndrome. Phytomedicine 11 (2004) 469. Reprintpermission granted by the principal author and Huber, RightsManager Journals, Elsevier GmbH, E-mail: m.huberelsevier. © 2004Elsevier GmbH. All rights reserved. www.elsevier.de/phymed.A cholinergic therapy based on the use of Donepezil has reported goodresults in four adults with Down Syndrome (DS) (Kishnani et al.,1999). Kishnani and colleagues took into consideration similaritiesbetween the neurobiology of Alzheimer's Disease and of DS.Ginkgo biloba (standardized extract EGb 761) has shown the sameefficacy as Donepezil and other cholinesterase inhibitors in thetreatment of dementia (Wettstein, 2000). Ginkgo standardized extractalso seems to have a direct effect on the cholinergic system (DeFeudisand Drieu, 2000). In individuals with DS, therapy with standardisedGinkgo biloba extract could be an effective aid to cognitive andsocial skills intervention.We examined two young patients with trisomy 21 (diagnosed bycytogenetic analysis) to verify this hypothesis. They were notaffected by cardiac or other malformations nor had they othersignificant medical conditions. A psychiatric assessment was performedusing a semi-structured psychiatric interview for children andadolescents (K-SADS PL 1.0). It was necessary to exclude any bias dueto change in psychiatric conditions during therapy. Patients did notshow significant psychopathology. Mental retardation was diagnosedthrough the use of the age-appropriate Wechsler Scale, and an Italiancomplete version of the Vineland Adaptive Behaviour Scale.Medication was given during the summer holidays, when school,rehabilitation and educational training are suspended. In both casesinformed consent was obtained from parents.The first case involved a boy 10 years 11 months old with an I.Q. of40 and a Vineland scale total score of 455. He received standardisedextract of Ginkgo biloba (GK 501, Pharmaton), at a dose of 80 mg everymorning for 11 weeks.After this period, a Vineland retest showed an improvement in totalscore: 497. This child showed a major improvement in personal autonomywith an increase of 16: he learned to put on his shoes and to tie hisshoelaces. In social behaviour, an improvement of 8 points wasrecorded: he began to make friends spontaneously.The second patient was aged 17 years and 8 months, and had an I.Q. of44; the Vineland scale total score was 721. The patient receivedGinkgo biloba GK 501, at a dose of 120mg every morning for 13 weeks.Vineland retest showed an improvement, with a total score of 758. Anincrease of 8 points in writing scores was recorded; the boy beganmemorising and writing more than 20 words and writing little notesspontaneously. The patient showed an improvement in imitation score (8points). He had a better control of impulsiveness and anger.None of the two patients had side effects during therapy.These results seem to indicate that, in DS patients, GK 501 therapycould be effective on improving social and academic skills. Usually,DS people do not show spontaneous improvement in the space of 3months. A double blind controlled trial is of course needed todemonstrate the efficacy, safety and effectiveness of Ginkgo bilobaextract in DS.ReferencesDeFeudis, F.V., Drieu, K., 2000. Ginkgo biloba extract (EGb 761) andCNS functions: basic studies and clinical applications. Curr. DrugTargets 1 (1), 25-58.Kishnani, P.S., Sullivan, J.A., Walter, B.K., Spiridigliozzi, G.A.,Doraiswamy, P.M., Krishnan, K.R., 1999. Cholinergic therapy for Down'sSyndrome. Lancet 2, 353 (9158), 1064-1065.Wettstein, A., 2000. Cholinesterase inhibitors and Ginkgo extracts-arethey comparable in the treatment of dementia? Comparison of publishedplacebo-controlled efficacy studies of at least six months' duration.Phytomedicine 6 (6), 393-401. http://www.altonweb.com/cs/downsyndrome/index.htm?page=feb05.html

----------

http://www.jneuroinflammation.com/content/1/1/4

-----------

"Ginkgo works on the glutamate receptor. That receptor in the area of the hippocampus acts like a gate. The hippocampus is the area of the brain used for short term memory storage for up to 90 days though some studies show it to be up to a year. The gate is held open for a certain amount of time allowing short term memory in. In DS this receptor like most others is decreased so the gate opening is short and infrequent limiting short term memory acquisition. Ginkgo (made up of two terpine hydrides named ginkgolides and bilobides) works mildly to increase the gate time. Other, more effective, medications are in the pipeline as they are ideal Alzheimer drugs and therefore good for DS but these are not getting into production in a timely manner. Ginkgo is easily available with few if any side effects so it is used.

Dr. Leichtman"

------------

http://www.mercola.com/2006/dec/9/more-evidence-ginkgo-biloba-works-just-as-well-as-dementia-drugs.htm

http://www.drugdigest.org/DD/DVH/HerbsWho/0,3923,4017|Ginkgo,00.html

www.curingdownsyndrome.com

---------

http://www.altonweb.com/cs/downsyndrome/index.htm?page=feb07.html

9th World Down Syndrome Congress

Exploring the Neurobiological Basis for Cognitive Problems in Down Syndrome. Mobley, M.D., Ph.D. Stanford University School of Medicine. 9th World Down Syndrome Congress Presentation. Vancouver, B.C., Canada.

Down syndrome (DS) is caused by an extra copy (i.e., trisomy) of chromosome 21. Cognitive problems are experienced by people with DS throughout the lifespan. Children with DS show varying degrees of cognitive slowing. All people over the age of 40 years with DS show the neuropathology of Alzheimer's disease (AD) and many people suffer further cognitive decline (i.e., dementia) in their 60s and beyond. Until very recently, scientists saw the problems posed by an extra copy of an entire chromosome as too complex to analyze. Moreover, it was believed that since DS problems arose during development, little could be done to reverse the damage. Fortunately, recent scientific advances have brought new tools and concepts to the biology of DS. Using modern genetic technologies and the results of the human genome project, it is now possible to define the gene(s) responsible for any atypical feature in people with DS. Moreover, advances in neuroscience have made it feasible to discover these changes, elucidate their mechanism, and develop new pharmacological therapies. The insights developed through this research not only will help children with DS, but also will have a direct impact on new treatments for Alzheimer's disease. One cause of cognitive problems in DS evident from structural and functional studies is that the hippocampus-a brain region whose function is critical for brain regions. Also, we know that basal forebrain cholinergic neurons (BFCNs), which innervate the hippocampus and are critically important for learning and memory, are abnormal in both children and adults. It is therefore believed that BFCN dysfunction and degeneration contribute to developmental and age-related problems in cognition in both Down syndrome and Alzheimer's disease. But as yet there is no insight into how this is caused or how to ameliorate dysfunction of BFCNs and thereby enhance cognition.

The hypothesis that guides our work is that each cognitive abnormality in DS is due directly or indirectly to increased expression of a specific gene(s) on chromosome 21. By discovering the responsible gene(s) it may be possible to prevent or rescue the defect. Our studies place a particular emphasis on hippocampal circuits that mediate learning and memory. We examine mouse models of DS and define changes that recapitulate those seen in DS. The Ts65Dn mouse model has a third copy of a portion of mouse chromosome 16 which is very similar to human chromosome 21 in that it contains an extra copy of about 140 homologous genes. Importantly, these mice show abnormalities in cognitive tasks mediated by hippocampus, including defects in spatial learning and memory.

Studies in young mice have shown abnormalities in the structure and function of synapses that closely resemble those in people with DS. Our findings point to an increase in inhibitory neurotransmission that could compromise circuit function and impair learning and memory. We will discuss the findings and indicate how ongoing studies are attempting to understand and overcome the abnormalities detected. BFCNs are responsible for the cholinergic innervation of the hippocampus. Cholinergic innervation of the hippocampus is known to be important for short-term spatial learning and memory. Atrophy and loss of BFCNs are consistent features in people with DS and AD, a change believed to contribute significantly to the resulting cognitive difficulties. The Ts65Dn mouse exhibits the abnormality, showing progressive age-related atrophy and loss of BFCNs within the hippocampus. We have explored the cause for BFCN degeneration, gathering evidence that failed signaling of nerve growth factor (NGF) is important. NGF, which is produced in the hippocampus, is critical for the normal development of BFCNs and for maintenance of their integrity and innervation of the hippocampus. We discovered that in DS mice there is marked disruption of NGF retrograde transport to about 10% of normal levels. To ask whether or not this was significant, we bypassed the defect by administering NGF directly to the cell bodies of BFCNs. This resulted in complete reversal of the atrophy and apparent loss of BFCNs.

Slides courtesy of Mobley, M.D., Ph.D.

These data strongly supported the view that in the absence of sufficient retrograde transport of NGF within signaling endosomes, BFCNs become shrunken and dysfunctional, but do not die. We found that a region containing about 40 genes was needed for the defect in NGF transport and BFCN degeneration. This region included the gene for amyloid precursor protein (App). To test for what role App might play, Ts65Dn mice were mated with mice heterozygous for deletion of App. The offspring included TsSDn mice with either 3 or 2 copies of APP. The mice with two copies of App showed no defect in BFCN size. Importantly, deleting the third copy of App also markedly increased NGF transport. These data are evidence for an important role for the third copy of App. This suggests the pathogenetic sequence: Increased APP Expression ¢ª Decreased NGF Transport ¢ª Loss of BFCNs ¢ª Abnormal Cognition. Thus, even in the context of a complex genetic lesion, overexpression of but one gene can produce important changes. We are now exploring the mechanism for disruption in NGF transport and are beginning studies to show whether or not reducing APP protein levels can prevent or reverse the deficits in transport and BFCNs.

Exploring the Neurobiological Basis for Cognitive Problems in Down Syndrome. Commentary by Dr. Cody.

I would like to extend my thanks to Dr. Mobley's Stanford University Down Syndrome Research team. They are moving research into uncharted territory and uncovering positive discoveries for more treatment options. (Hippocampal Long-Term Potentiation Suppressed by Increased Inhibition in the Ts65Dn Mouse, a Genetic Model of Down Syndrome. J Neurosci. 2004 Sep 15; 24(37):8153-60)

This is the most exciting time in the history of DS research with the advent of a genetically engineered DS mouse, this means to add or subtract a gene or genes to/from that mouse.

Produce mice that have DS. That means mice with an extra copy of the smallest chromosome, which exhibit DS phenotypes. Produce second and third generation DS mice in where extra segments of the extra chromosome are deleted. Then determine if the absence of that segment reduces or eliminates the DS phenotypes/abnormalities.

With these technical advances, delivering a treatment is possible.

Stanford first looked at the brain region critical for learning and memory. They examined structure, as well as, function. It turns out they go hand in hand.

Two problems emerged. The shape of the end of the nerve is too big and the nerves are not being used. Like muscles, without use, the nerves become weak and do not maintain their proper shape.

This may sound impossible to treat but the scientists figured out why the nerves were not working. The GABA receptor is turned on all the time, shutting down the rest of the nervous system. Stanford is now working on developing a pharmaceutical product that will turn GABA down to the right level. In the meantime, the herb Ginkgo Biloba, which has been used for years to increase memory in the elderly, is a mild GABA antagonist, i.e., turns GABA down. (Bilobalide, a sesquiterpene trilactone from Ginkgo biloba, is an antagonist at recombinant ¦Á1¦Â2¦Ã2L GABA(A) receptors. Eur J Pharmacol. 2003 Mar 7;464(1):1-8)

The University of Sydney has been studying the GABA receptor in detail and concluded that Ginkgo Biloba is a safe, effective GABA antagonist. (Ginkgolides, diterpene trilactones of Ginkgo biloba, as antagonists at recombinant ¦Á1¦Â2¦Ã2L GABA(A) receptors. Eur J Pharmacol. 2004 Jun 28; 494(2-3):131-8)

The next step being studied is why is there a lack of maintenance of the nerves? Nerves must be maintained with chemicals called growth factors. These growth factors (little packets of nerve nutrition) are transported down a nerve 'highway' if you will. In the DS mouse model, the scientists discovered the highway was shut down and no growth factors made it to the nerves. This leaves the nerves vulnerable and unable to survive.

The good news is that when the highway was bypassed and growth factors were placed directly on the nerves; the nerves revived as if they had been sleeping, not dead. Stanford used the DS mouse to narrow down the responsible gene(s). The likely candidate is a gene called APP. This acronym may be familiar because it is being studied extensively in Alzheimer's disease.

Treatment options include turning down the expression of APP or increasing availability of growth factors.

Dr. Mobley's presentation truly gives us insight into new avenues of treatment. At one time, Down syndrome was considered too complex to resolve but as with other medical mysteries, it is being unraveled by modern day science.

Dr. Cody, University of Texas Dental Branch 1992; Bachelors Degree in Biology from the University of Texas in Austin, 1988. Dr. Cody has a private practice in the Houston area that specializes in children with disabilities. She served on the Down Syndrome Research board 2004-5, spearheading the Adopt a Mouse fundraiser and is an advisor to the Down Syndrome Association of Houston. See: http://www.curingdownsyndrome.com.

Qadoshyah

*Got Down Syndrome?

www.gotdownsyndrome.net

From: Down Syndrome Treatment [mailto:Down Syndrome Treatment ] On Behalf Of rdavis900@...Sent: Monday, February 26, 2007 4:19 PMDown Syndrome Treatment Subject: Re: Drug treatment improves learning in mice with ...

Everyone keeps talking about ginko. I am going to research tonight after the kids are in bed. Do you have to worry about interactions with other medications? Sara is already taking Nutrivene D.....SO many questions? Does anyone have some information to offer so when I go searching I go in the right direction? Thank you! Marcy

AOL now offers free email to everyone. Find out more about what's free from AOL at AOL.com.

[Guest guest]

You may also find info in the files section and archives.

Qadoshyah

*Got Down Syndrome?

www.gotdownsyndrome.net

From: Down Syndrome Treatment [mailto:Down Syndrome Treatment ] On Behalf Of rdavis900@...Sent: Monday, February 26, 2007 4:19 PMDown Syndrome Treatment Subject: Re: Drug treatment improves learning in mice with ...

Everyone keeps talking about ginko. I am going to research tonight after the kids are in bed. Do you have to worry about interactions with other medications? Sara is already taking Nutrivene D.....SO many questions? Does anyone have some information to offer so when I go searching I go in the right direction? Thank you! Marcy

AOL now offers free email to everyone. Find out more about what's free from AOL at AOL.com.

[Guest guest]

There should be a lot of information in our message archives..just

go to the message section and type in ginko in the search box.

From:

Down Syndrome Treatment

[mailto:Down Syndrome Treatment ] On Behalf Of rdavis900@...

Sent: Monday, February 26, 2007 7:19 PM

Down Syndrome Treatment

Subject: Re: Drug treatment improves learning

in mice with ...

Everyone keeps talking about ginko. I am going to research tonight

after the kids are in bed. Do you have to worry about interactions with

other medications? Sara is already taking Nutrivene D.....SO many

questions? Does anyone have some information to offer so when I go searching

I go in the right direction? Thank you! Marcy

[Guest guest]

Marcy

there is a website on the subject of Ginkgo treatment for kids with

DS: www.curingdownsyndrome.com

Although I believe the name of the website definitely raises false

expectations, the information given is based on sound scientific

evidence. You'll also find dosage recommendations there.

Good luck,

/Switzerland

>

> There should be a lot of information in our message archives..just

go to the

> message section and type in ginko in the search box.

>

>

>

> From: Down Syndrome Treatment

> [mailto:Down Syndrome Treatment ] On Behalf Of

> rdavis900@...

> Sent: Monday, February 26, 2007 7:19 PM

> Down Syndrome Treatment

> Subject: Re: Drug treatment improves

learning in

> mice with ...

>

>

>

>

> Everyone keeps talking about ginko. I am going to research tonight

after the

> kids are in bed. Do you have to worry about interactions with other

> medications? Sara is already taking Nutrivene D.....SO many

questions? Does

> anyone have some information to offer so when I go searching I go in the

> right direction? Thank you! Marcy

>

[Guest guest]

Marcy

I forgot to say that there is a file called Bilobalide_GABA in the

files section. It explains how Ginkgo works in the brain. To put it

short, it suppresses excessive inhibitory signaling induced by a brain

chemical called GABA. While inhibitory signaling is nothing bad per se

(without it we'd be flooded with tons of unnecessary information and

our brains would be fried), it is increased in people with DS which at

least partly explains why they are slow in their reactions to sensory

stimuli, esp. auditive ones, and why memorizing and therefore

learning is so much more difficult. In contrast to all other known

drugs, including pentylenetetrazole or PTZ, the one that everyone is

speaking of in the news, it DOESN'T have any noteworthy side effects

and certainly doesn't induce seizures.

,

s dad/Switzerland

>

> There should be a lot of information in our message archives..just

go to the

> message section and type in ginko in the search box.

>

>

>

> From: Down Syndrome Treatment

> [mailto:Down Syndrome Treatment ] On Behalf Of

> rdavis900@...

> Sent: Monday, February 26, 2007 7:19 PM

> Down Syndrome Treatment

> Subject: Re: Drug treatment improves

learning in

> mice with ...

>

>

>

>

> Everyone keeps talking about ginko. I am going to research tonight

after the

> kids are in bed. Do you have to worry about interactions with other

> medications? Sara is already taking Nutrivene D.....SO many

questions? Does

> anyone have some information to offer so when I go searching I go in the

> right direction? Thank you! Marcy

>

[Guest guest]

Shirley,

I forgot to mention that there was actually a study done about the

effect of Ginkgo on people with DS, albeit a small one, but still, it

turned out pretty positive...(see below)

One of the participants was about ages with your son and he got

120mg/day. It's difficult to overdose, mind you. You could try

starting with 120mg and if you don't see any difference after a month

you could work up to the dosage stated by Dr. Leichtman.

All the best,

/Switzerland

***

Ginkgo biloba in Down Syndrome. Phytomedicine 11 (2004) 469. Reprint

permission granted by the principal author and Huber, Rights

Manager Journals, Elsevier GmbH, E-mail: m.huber@.... © 2004

Elsevier GmbH. All rights reserved. www.elsevier.de/phymed.

A cholinergic therapy based on the use of Donepezil has reported good

results in four adults with Down Syndrome (DS) (Kishnani et al.,

1999). Kishnani and colleagues took into consideration similarities

between the neurobiology of Alzheimer's Disease and of DS.

Ginkgo biloba (standardized extract EGb 761) has shown the same

efficacy as Donepezil and other cholinesterase inhibitors in the

treatment of dementia (Wettstein, 2000). Ginkgo standardized extract

also seems to have a direct effect on the cholinergic system (DeFeudis

and Drieu, 2000). In individuals with DS, therapy with standardised

Ginkgo biloba extract could be an effective aid to cognitive and

social skills intervention.

We examined two young patients with trisomy 21 (diagnosed by

cytogenetic analysis) to verify this hypothesis. They were not

affected by cardiac or other malformations nor had they other

significant medical conditions. A psychiatric assessment was performed

using a semi-structured psychiatric interview for children and

adolescents (K-SADS PL 1.0). It was necessary to exclude any bias due

to change in psychiatric conditions during therapy. Patients did not

show significant psychopathology. Mental retardation was diagnosed

through the use of the age-appropriate Wechsler Scale, and an Italian

complete version of the Vineland Adaptive Behaviour Scale.

Medication was given during the summer holidays, when school,

rehabilitation and educational training are suspended. In both cases

informed consent was obtained from parents.

The first case involved a boy 10 years 11 months old with an I.Q. of

40 and a Vineland scale total score of 455. He received standardised

extract of Ginkgo biloba (GK 501, Pharmaton), at a dose of 80 mg every

morning for 11 weeks.

After this period, a Vineland retest showed an improvement in total

score: 497. This child showed a major improvement in personal autonomy

with an increase of 16: he learned to put on his shoes and to tie his

shoelaces. In social behaviour, an improvement of 8 points was

recorded: he began to make friends spontaneously.

The second patient was aged 17 years and 8 months, and had an I.Q. of

44; the Vineland scale total score was 721. The patient received

Ginkgo biloba GK 501, at a dose of 120mg every morning for 13 weeks.

Vineland retest showed an improvement, with a total score of 758. An

increase of 8 points in writing scores was recorded; the boy began

memorising and writing more than 20 words and writing little notes

spontaneously. The patient showed an improvement in imitation score (8

points). He had a better control of impulsiveness and anger.

None of the two patients had side effects during therapy.

These results seem to indicate that, in DS patients, GK 501 therapy

could be effective on improving social and academic skills. Usually,

DS people do not show spontaneous improvement in the space of 3

months. A double blind controlled trial is of course needed to

demonstrate the efficacy, safety and effectiveness of Ginkgo biloba

extract in DS.

References

DeFeudis, F.V., Drieu, K., 2000. Ginkgo biloba extract (EGb 761) and

CNS functions: basic studies and clinical applications. Curr. Drug

Targets 1 (1), 25-58.

Kishnani, P.S., Sullivan, J.A., Walter, B.K., Spiridigliozzi, G.A.,

Doraiswamy, P.M., Krishnan, K.R., 1999. Cholinergic therapy for Down's

Syndrome. Lancet 2, 353 (9158), 1064-1065.

Wettstein, A., 2000. Cholinesterase inhibitors and Ginkgo extracts-are

they comparable in the treatment of dementia? Comparison of published

placebo-controlled efficacy studies of at least six months' duration.

Phytomedicine 6 (6), 393-401.

http://www.altonweb.com/cs/downsyndrome/index.htm?page=feb05.html

> >

> > There should be a lot of information in our message

archives..just

> go to the

> > message section and type in ginko in the search box.

> >

> >

> >

> > From: Down Syndrome Treatment

> > [mailto:Down Syndrome Treatment ] On Behalf Of

> > rdavis900@

> > Sent: Monday, February 26, 2007 7:19 PM

> > Down Syndrome Treatment

> > Subject: Re: Drug treatment improves

> learning in

> > mice with ...

> >

> >

> >

> >

> > Everyone keeps talking about ginko. I am going to research

tonight

> after the

> > kids are in bed. Do you have to worry about interactions

with other

> > medications? Sara is already taking Nutrivene D.....SO many

> questions? Does

> > anyone have some information to offer so when I go searching

I go in the

> > right direction? Thank you! Marcy

> >

>

>

>

>

>

>

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