SCHAFER AUTISM REPORT "Healing Autism:

No Finer a Cause on the Planet"

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August 27, 2002 CALENDAR LISTING: EVENTS@doitnow.com

RESEARCH

* Serotonin Transporter Gene, Hyperserotoninemia And Autism

* More On The Reelin Gene And Autism

* A Genomewide Screen for Autism-Spectrum Disorders

* Relation of Childhood Gastrointestinal Disorders To Autism

* Promise of Stem Cell Research Still Years Away

Serotonin Transporter Gene, Hyperserotoninemia And Autism 'Serotonin transporter gene promoter variants do not explain the hyperserotoninemia in autistic children'

ds=12192626&dopt=Abstract <- - address ends here.

Persico AM, Pascucci T, Puglisi-Allegra S, Militerni R, Bravaccio C, Schneider C, Melmed R, Trillo S, Montecchi F, Palermo M, Rabinowitz D, Reichelt KL, Conciatori M, Marino R, Keller F. Laboratory of Neuroscience, Interdisciplinary Center for Biomedical Research (CIR), Universita 'Campus Bio-Medico', Via Longoni 83, I-00155 Rome, Italy.

Autism is a biologically-heterogeneous disease.

Distinct subgroups of autistic patients may be marked by intermediate phenotypes, such as elevated serotonin (5-HT) blood levels, potentially associated with different underlying disease mechanisms.

This could lead to inconsistent genetic association results, such as those of prior studies on serotonin transporter (5-HTT) gene promoter variants and autistic disorder.

Contributions of 5-HTT gene promoter alleles to 5-HT blood levels were thus investigated in 134 autistic patients and 291 first-degree relatives.

Mean 5-HT blood levels are 11% higher in autistic patients carrying the L/L genotype, compared to patients with the S/S or S/L genotype; this trend is not observed in first-degree relatives.

The probability of inheriting L or S alleles is significantly enhanced in patients with 5-HT blood levels above or below the mean, respectively (P < 0.05), but quantitative TDT analyses yield a non-significant trend (P = 0.10), as this polymorphism explains only 2.5% of the variance in 5-HT blood levels of autistic patients.

In conclusion, 5-HTT gene promoter variants seemingly exert a small effect on 5-HT blood levels in autistic children, which largely does not account for hyperserotoninemia.

Nonetheless, the inconsistent outcome of prior association studies could partly stem from a selection bias of hyper- or hypo-serotoninemic probands.

PMID: 12192626 [PubMed - in process]

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More On The Reelin Gene And Autism

'Absence of association between a polymorphic GGC repeat in the 5' untranslated region of the reelin gene and autism'

ds=12192627&dopt=Abstract <- - address ends here.

Krebs MO, Betancur C, Leroy S, Bourdel MC, Gillberg C, Leboyer M; The Paris Autism Research International Sibpair (PARIS) Study. INSERM E0117, University of Paris V, Department of Mental Health and Therapeutics, Sainte-Anne Hospital, 75014 Paris, France.

Autism is a complex neurodevelopmental disorder with severe cognitive and communication disabilities, that has a strong genetic predisposition.(1) Reelin, a protein involved in neuronal migration during development, is encoded by a gene located on 7q22,(2) within the candidate region on 7q showing increased allele sharing in previous genome scans.(3-8)

A case/control and family-based association study recently reported a positive association between a trinucleotide repeat polymorphism (GGC) located in the 5' untranslated region (UTR) of the reelin gene and

autism.(9) We performed a transmission disequilibrium test (TDT) analysis of the 5'UTR polymorphism in 167 families including 218 affected subjects (117 trios and 50 affected sib pairs) and found no evidence of linkage/association.

Our results do not support previous findings and suggest that this GGC polymorphism of the reelin gene is unlikely to be a major susceptibility factor in autism and/or genetic heterogeneity.

PMID: 12192627 [PubMed - in process]

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A Genomewide Screen for Autism-Spectrum Disorders:

Evidence for a Major Susceptibility Locus on Chromosome 3q25-27.

ds=12192642&dopt=Abstract <- - address ends here.

Auranen M, Vanhala R, Varilo T, Ayers K, Kempas E, Ylisaukko-Oja T, Sinsheimer JS, Peltonen L, Jarvela I I. Department of Molecular Medicine, National Public Health Institute, and Department of Medical Genetics, University of Helsinki, Helsinki, Finland.

To identify genetic loci for autism-spectrum disorders, we have performed a two-stage genomewide scan in 38 Finnish families.

The detailed clinical examination of all family members revealed infantile autism, but also Asperger syndrome (AS) and developmental dysphasia, in the same set of families.

The most significant evidence for linkage was found on chromosome 3q25-27, with a maximum two-point LOD score of 4.31 (Z(max )(dom)) for D3S3037, using infantile autism and AS as an affection status.

Six markers flanking over a 5-cM region on 3q gave Z(max dom) >3, and a maximum parametric multipoint LOD score (MLS) of 4.81 was obtained in the vicinity of D3S3715 and D3S3037.

Association, linkage disequilibrium, and haplotype analyses provided some evidence for shared ancestor alleles on this chromosomal region among affected individuals, especially in the regional subisolate.

Additional potential susceptibility loci with two-point LOD scores >2 were observed on chromosomes 1q21-22 and 7q.

The region on 1q21-22 overlaps with the previously reported candidate region for infantile autism and schizophrenia, whereas the region on chromosome 7q provided evidence for linkage 58 cM distally from the previously described autism susceptibility locus (AUTS1).

PMID: 12192642 [PubMed - as supplied by publisher]

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Relation of Childhood Gastrointestinal Disorders To Autism: Nested case-control study using data from the UK General Practice Research Database.

ds=12193358&dopt=Abstract <- - address ends here.

Black C, Kaye JA, Jick H.

Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, MA 02421, USA.

Objectives: To assess whether children with autism are more likely to have a history of gastrointestinal disorders than children without autism.

Design: Nested case-control study.

Setting: UK General Practice Research Database.

Subjects: Children born after 1 January 1988 and registered with the General Practice Research Database within 6 months of birth.

Outcome measures: Chronic inflammation of the gastrointestinal tract, coeliac disease, food intolerance, and recurrent gastrointestinal symptoms recorded by the general practitioner.

Results: 9 of 96 (9%) children with a diagnosis of autism (cases) and 41 of 449 (9%) children without autism (matched controls) had a history of gastrointestinal disorders before the index date (the date of first recorded diagnosis of autism in the cases and the same date for controls).

The estimated odds ratio for a history of gastrointestinal disorders among children with autism compared with children without autism was 1.0 (95% confidence interval 0.5 to 2.2).

Conclusions: No evidence was found that children with autism were more likely than children without autism to have had defined gastrointestinal disorders at any time before their diagnosis of autism.

PMID: 12193358 [PubMed - in process]

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Promise of Stem Cell Research Still Years Away

Political climate may be chilling progress on embryonic stem cell research.

In the year since President Bush announced his administration's guidelines for the federal funding of stem cell research, the intensity of the debate over the moral and ethical implications has not cooled much.

As the two sides duke it out before Congress and in the media, one fact is often left behind -- any benefit from this research is years away. At least five years, and perhaps even 10, according to one leading researcher.

"I think there is great promise for these cells to treat diseases, but we're still a long way from that," said Catherine Verfaillie, MD, director of the University of Minnesota Stem Cell Institute in Minneapolis. "There's a lot of hope out there, but I think it's going to take a while."

Using stem cells for tissue regeneration to treat Parkinson's disease or diabetes may be possible "within the next decade or so," Dr. Verfaillie said, but it's likely that the technology will first be used to discover new drugs or for drug toxicity screening.

The promise of stem cell therapies is that one day physicians will be able to replace diseased cells with functional, healthy ones to treat cancer, diabetes, spinal cord injuries and other afflictions. Many scientists believe stem cells from embryos hold the most promise for providing the cellular raw materials for these therapies. But research by Dr. Verfaillie and others is showing that adults' stem cells may be able to achieve similar results.

On Aug. 9, 2001, the president made one of his first major policy announcements when he announced that federal money would be made available for human embryonic stem cell research, but that funding would be limited only to research done on 64 cell lines already in existence.

Only 9 labs applied for first-round federal grants on embryonic stem cell research.

These 64 lines, also called "colonies," met certain qualifications outlined by the president: They were derived from embryos created for reproductive purposes and were no longer needed for those purposes; informed consent was obtained for the donation of the embryo; and no financial inducements were provided for donation of the embryo.

Since that announcement, it has been discovered that there are actually 78 existing colonies that meet the president's criteria. However, many of these remain off-limits to researchers while lawyers work out intellectual property issues.

Also, according to the Assn. of American Medical Colleges, only one stem-cell line owner is currently sharing lines with medical school researchers. All of this adds up to a "chilling effect" on scientists, which -- according to the Washington Post -- has resulted in only nine laboratories applying for the first round of federal grants.

Although human embryonic stem cell research may be limited, animal-based research remains well-funded at both the private and public levels.

National Institutes of Health spokesman Don Robusky said funding for adult stem cell research for this fiscal year was just under $300 million, while funding for embryonic stem cell research -- at this point, at least -- is a function of how many researchers apply for it.

"All of the funding depends on the grant applications we receive that are good enough to be funded," he said.

Only one stem-cell line owner is sharing lines with medical school researchers.

Robusky said the federal government has awarded about $5.1 million in either "infrastructure grants" or "administrative supplements" to help institutions prepare for conducting human embryonic stem cell research.

While government funding remains somewhat tentative, more money may be coming from private sources. Much of this funding, however, may go to researchers outside of the United States.

The Juvenile Diabetes Research Foundation announced last month that it seeks to raise $20 million to fund both embryonic and adult stem cell research in eight countries. It also entered into a $7.5 million partnership with the Swedish Diabetes Assn. Research Foundation to pay for stem cell research in that country.

The Michael J. Fox Foundation for Parkinson's Research has also awarded $4.4 million in grants to fund nine stem cell research projects going on in both the United States and Sweden.

Lobbying efforts remain strong

American politicians are being lobbied to both increase and halt support of embryonic stem cell research. Opposition comes from groups who say embryonic stem cell research creates human life only to destroy it. In fact, the National Right to Life Committee has started a "No Embryo Farms Campaign," which aims to halt experiments involving human embryo cloning technology.

The right to life movement has championed the adult stem cell research done by Dr. Verfaillie and others as a moral alternative to using embryonic stem cells.

Funding for adult stem cell research in fiscal 2002 was $300 million.

In an essay published in the Kentucky Post, Michael Janocik with the Right to Life Educational Foundation of Kentucky outlined his organization's stance while praising adult stem cell research being conducted at the University of Louisville.

"It should come as no surprise that those who respect human life in the womb do so also in the laboratory. We know that an assault on any innocent human life is an assault on every human life," Janocik wrote. "We urge [the university] to relentlessly pursue the morally superior avenue of adult stem cell research and we want nothing less than a complete restoration of health to those who live with unspeakable suffering. By reject the utilitarian seductions of human cloning research, we will go a long way toward the restoration of our dignity."

Noting that these organizations who champion her work have never even spoken with her, Dr. Verfaillie maintains that both types of stem cell research need to continue because it is unknown which cells will work best for which potential therapies.

"There are way too many basic questions unanswered," she said.

Although embryonic stem cell and cloning issues are often linked, Dr. Verfaillie said that probably "99.9% or more" of research scientists oppose reproductive cloning.

She added that her institute does not work in a vacuum because an ethics advisory board keeps an eye on the research being done there. "It's important to have an open communication with scientists and nonscientists, and to have a sounding board to see if what we're doing is the right thing to do or not," Dr. Verfaillie said.

The Juvenile Diabetes Research Foundation apparently agrees, and has called on President Bush to hold a meeting to open up communication between government officials, researchers and the owners of the approved stem cell lines.

Spokeswomen for both JDRF and the Coalition for the Advancement of Medical Research said they met with Health and Human Services Secretary Tommy Thompson on Aug. 9 to discuss stem cell issues, but they have not yet heard back from the administration on their request for a "stakeholder meeting" to remove the obstacles impeding stem cell research.

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Additional information:

Weblink

Coalition for the Advancement of Medical Research

Juvenile Diabetes Research Foundation stem cell update

Michael J. Fox Foundation for Parkinson's Research cell line initiative

National Right to Life Committee No Embryo Farms! campaign

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