Monica Coenraads, vice president of research for RSRF and Craig Robertson, executive director of RSRF were in attendance to bring us up to date on RSRF development and research.


The presentation opened with the video produced by RSRF and used in their fund-raising efforts. Comments were made regarding the video and Craig informed us that the video is scheduled to be revised in 2006.

Craig explained that RSRF's mission is very focused. It is to fund, promote and accelerate biomedical research for the treatment and cure of Rett syndrome.

2.6 million dollars was raised in 2004 by RSRF. 90% of this was used for research, 5.3% for scientific meetings and 4.7% on education. Since 1999, 6.5 Million dollars in research has been funded. In 2004, the New England area raised $670,000 for RSRF. 75% of this money is from special events.

RSRF, IRSA and the National Institute of Health (NIH) have recently joined in some collaborative efforts to advance Rett research.


Monica spoke regarding RSRF research efforts. There is presently a three pronged approach to money distribution to maximize funding flexibility and to ensure a well balanced portfolio of projects. Post-doc and certain other researchers receive "seed grants". GEAR grants (Grants of Excellence for Accelerated Rett Research) are given to researchers to work on specific projects identified by RSRF. Doctors Zoghbi, Jaenisch, Bird and Heintz are presently receiving GEAR Grants. NIH, IRSA and RSRF collaborative funding make up the third prong of research funding. NIH is contributing five million dollars to Rett research.

There are now four research focus areas. These include replacing neuronal MECP2 through gene therapy, activating silent MECP2 on inactive sites, and defining cell populations that are effected by MECP2 deficiency.

The functions of MECP2 are believed to be (1) a role in gene expression; turns downstream genes off (ex. BDNF and DLX5), (2) facilitates 3D folding of DNA into nucleus, (3) strengthens connections between brain cells aiding synaptic plasticity.

Current estimates are that there are presently 15,000 Rett cases in the United States and 331,000 world wide. This is based on 1 in 10,000 female births. Rett is considered the leading genetic cause of severe impairment in girls. Mutations in MECP2 have been found in some cases of autism, schizophrenia, learning disabilities and Angelman syndrome. Of the autism spectrum disorders, only Rett syndrome is known to have a genetic cause.

The annual RSRF meeting will be held in Chicago in June for three days, chaired by Drs. Bird and Zoghbi.

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April 14, 2005

Dr. Genevieve Laforet, M.D., Ph.D. spoke to us about her ongoing research at University of Massachusetts Medical School in Worcester. Her research is funded by RSRF. RSAM is her research sponsor.

Dr. Laforet is looking at theophylline, a drug used to treat asthma, and its potential in correcting neurochemical problems in Rett syndrome. When theophylline is applied to isolated mouse neurons in a petri dish, the desired effect of increased HDAC activity was seen. The next step was to try to see the effect of theophylline on HDAC stimulation in live mice. HDAC is a protein and Dr. Laforet explains in her abstract, "If there were some way to stimulate these HDAC's directly, we could bypass the MeCP2 malfunction and potentially prevent or reduce the severity of RTT."

Mice received the drug theophylline either in their drinking water or in time released pellets. After two and a half weeks the mice brains are harvested. It was found that the drug does get into the brain. A 15% increase in HDAC activity was seen in brains of mice receiving the pellets. Therefore the drug is getting into the brain and yielding the desired biochemical change. The effective dosage of the drug must be determined and the window of time when the drug should be given. Next, Dr. Laforet wants to try the drug with MeCP2 deficient mice.

Dr. Laforet spoke about some of the characteristics of MeCP2 deficient mice. MeCP2 deficient mice are lacking the typical social interactions seen in mice. They also function differently in maze studies. MeCP2 deficient mice also seem to have an abnormal sleep-wake cycle. Changes in these characteristics can be used to assess the effect of the drug under study. It was also noted that MeCP2 mice are generally smaller and more aggressive than normal mice.

Dr. Laforet presented additional information on her experimental work and on her experiences breeding MeCP2 deficient mice. Following the presentation there was a question and answer session.

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November 11, 2004

The evening's program was a presentation by the parents of four women with Rett syndrome. They presented information related to their daughters' out of home placements. Each family has a daughter who is now over twenty-two and is in a living situation outside the family home.

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April 8, 2004

Monica Coenraads, Rett Syndrome Research Foundation Vice-President of Research and Craig Robertson, Rett Syndrome Research Foundation Executive Director were present at our meeting to make presentations to the group.


The following are highlights from Craig’s presentation.

Craig introduced himself and told us that he joined RSRF this past December. He formerly did fundraising and development for the Muscular Dystrophy Association and the Myeloma Organization. He stated that there are now estimated to be 20,000 girls in the United States with Rett syndrome.

RSRF has now raised over two million dollars for Rett research and is now in the top 6% of fund-raising organizations. 90% of the funds raised by RSRF go directly to research. RSRF is presently or has funded every key Rett (RTT) researcher and is now the world’s number one private financial supporter of RTT research. Nearly 20% of research funds have gone to researchers in the New England area.

Sixty-eight grant proposals were submitted to RSRF for the upcoming year. This number has been narrowed down to twenty-seven and final decisions on recipients will be made at the June research symposium. Grants from RSRF are usually “seed grants” which allow researchers to begin pursuit of a line of research. They can subsequently apply to NIH for further funding after they have initiated their research.

Despite a national decline in charitable giving, RSRF donations have increased. Fifteen major fund raising events are scheduled throughout the country in 2004. There are five Strollathon events planned as well as festivals or galas in six cities. Some of the larger national companies supporting these events are Coca-Cola, Stride Rite and Re Max.


The following are highlights from Monica’s presentation of Rett research.

The MeCP2 mutation has been found in 85% of RTT patients tested and is considered the leading cause of Rett syndrome. The other 15% may be testing negative because present technology cannot detect the mutation. 99.9% of RTT cases are sporadic mutations and most likely paternal in origin. Somatic mosaicism (where the mutation occurs during cell division) and familial maternal mutation (mother has a 50% chance of passing on the mutation) and germ line mosaicism (mutation in egg cells only) cause the remaining small number of RTT cases. There are now seventeen reported cases of RTT occurring in males. MeCP2 mutations have also been found in individuals with autism, schizophrenia, learning disabilities, neonatal encephalopathy and Angelman’s.

There are presently animal models that have been genetically engineered to aid in RTT research. There are MeCP2 mutant mice, frogs, zebra fish and fruit flies. A brief video was shown of mice displaying “hand” movements similar to those seen in girls with Rett syndrome. The search for “druggable targets” was discussed as well as the very newest research. A recently published paper presents the discovery of an additional form of MeCP2 and this week a paper was published discussing the reversal of RTT symptoms when non-mutated MeCP is given to RTT mice soon after birth.

There was time for a question and answer session and general discussion following Monica and Craig’s well-received presentations.