Rettsyndrome.org, a leading private funder of Rett syndrome research, will award Jeannie T. Lee, MD, PhD, of Massachusetts General Hospital in Boston a $600,000, two-year Advanced Neurotherapeutic Grant of Excellence (ANGEL) to focus on reactivating the silent X chromosome in Rett.
It also will award a two-year $250,000 Mentored Clinical Fellowship to Davut Pehlivan, PhD, of Baylor College of Medicine to develop an assessment tool for MECP2 Duplication syndrome (MDS), a severe Rett-related neurological and developmental disorder that occurs almost exclusively in males.
Rett, which mostly affects females, is caused by a mutation on the MECP2 gene located in the X chromosome that instructs production of the MECP2 protein (methyl-CpG binding protein 2). The protein helps regulate nerve cell function and development.
Using a female Rett mouse model her team developed, Lee’s project involves activation of the silent X chromosome to restore brain MECP2 levels. Rett patients have one X chromosome with a defective MECP2 gene and one X chromosome with a normal gene copy. Nearly always, the healthy X chromosome is inactive or silent. Based on earlier work, Lee has said that even partial restoration of MECP2 levels may be beneficial in treating symptoms.
”I believe that a specific treatment for Rett syndrome is within reach,” Lee said in a press release. “We are very encouraged by (our) findings and believe that an X-reactivation approach can be both efficacious and safe. We hope to develop and optimize new therapeutics for the treatment of Rett.”
This is Lee’s second Rettsyndrome.org grant.
”We are very proud to continue funding Dr. Lee’s exciting work in X reactivation,” said Melissa Kennedy, the organization’s executive director. “She is one of the most respected and promising researchers in the field, and we are hopeful that her research will lead to a treatment or a cure for thousands living with Rett syndrome.”
MECP2 Duplication syndrome occurs when there is an extra copy of the MECP2 gene in each cell, caused by a duplication of genetic material on one of the arms of the X chromosome. Such duplication leads to production of too much MECP2 protein, resulting in dysfunctional regulation of other genes. In turn, this disrupts normal brain activity.
A pediatric neurologist, Pehlivan will work to create an assessment tool that can help with diagnosis and measure MDS severity and progression. The hope is that it also will be useful in evaluating therapy effectiveness. The team also plans to develop a biomarker that could be used in clinical trial evaluations.
”The fellowship that Rettsyndrome.org has funded will make a world of difference for Dr. Pehlivan and the Rett community,” said Pehlivan team member Daniel Glaze, MD, of Texas Children’s Hospital.