Dr. Alan Percy reviews lab data on new Rett syndrome drug.Dr. Alan Percy reviews lab data on new Rett syndrome drug.A recently concluded study of an experimental drug for Rett syndrome showed promising results, according to the drug’s manufacturer, Neuren Pharmaceuticals of Melbourne, Australia. The University of Alabama at Birmingham was one of three study sites for the drug, known as NNZ-2566.

Neuren announced Nov. 12 that the Phase II study had achieved its primary endpoint as two dose levels of NNZ-2566 were tolerated well after 28 days of treatment and no safety concerns were identified. Further, the company reported that the higher of two doses studied exceeded the pre-specified criteria for improvement in core efficacy measures compared with placebo.

There are currently no approved medicines for the treatment of Rett syndrome, a severe neurological disorder caused by mutations of the MECP2 gene on the X chromosome. Rett syndrome is a post-natal neurological disorder that occurs almost exclusively in females following apparently normal development for the first six months of life. Typically, between 6 to 18 months of age, patients experience a period of rapid clinical decline that stabilizes later in life.

There are approximately 10,000 to 20,000 females with Rett syndrome in the United States and more than 50,000 worldwide.

"The results of this trial suggest a very promising   proof of concept as we continue on the pathway to develop a disease-altering treatment for girls and women with Rett syndrome."
“The results of this trial suggest a very promising proof of concept as we continue on the pathway to develop a disease-altering treatment for girls and women with Rett syndrome,” said Alan Percy, M.D., professor of pediatric neurology in the UAB School of Medicine and one of the trial investigators.

This was the first multisite, sponsor-led clinical trial in Rett syndrome and the first trial in an adolescent and adult population, according to Neuren. In addition to UAB, the other study sites were the Baylor College of Medicine and Gillette Children’s Specialty Healthcare.

The study enrolled 53 subjects ages 16-45 years in the double-blind placebo-controlled trial. Two different dose levels of NNZ-2566 were tested: 35mg/kg twice per day and 70mg/kg twice per day. The dosage form was a strawberry-flavored liquid that was taken orally.

“These are exciting times for Rett syndrome, and this trial firmly sets our rudder in the water for the near future,” said Steven Kaminsky, Ph.D., the chief science officer for the International Rett Syndrome Foundation. “The results will enable engagement with the FDA on the further development of NNZ-2566. This is what we, as the Rett community, have been hoping for.” Contact Bob Shepard at UAB News for more information.
Dr. Brian Sims receives the 2014 Civitan McNulty Scientist Award for CIRC Director Dr. Harald Sontheimer.Dr. Brian Sims receives the 2014 Civitan McNulty Scientist Award from CIRC Director Dr. Harald Sontheimer.
Brian Sims, M.D., Ph.D., Associate Professor in the UAB Department of Pediatrics was named the 2014 McNulty Civitan Scientist in ceremonies on November 6, 2014 at the UAB Civitan International Research Center. Dr. Sims will receive a $50,000 grant to support his research efforts at UAB. Dr. Sims completed his Ph.D. and M.D. degrees in 1999 and 2000 respectively at the University of Alabama Birmingham followed by a clinical research fellowship at Washington University School of Medicine. He received the American Academy of Pediatrics Neonatal Resuscitation Program Young Investigators Award in 2003 and the Robert Wood Johnson Foundation’s Harold Amos Medical Faculty Development Program Scholarship for 2005-2009. Dr. Sims is a board certified neonatologist affiliated with the University of Alabama Birmingham and Children’s Hospital of Alabama. In addition to his ongoing clinical schedule, Dr. Sims has served as an active mentor to a number of undergraduate and graduate students whose projects coincide with his major research interest in understanding the cellular mechanisms involved in premature brain injury. The McNulty Scientist Award is named in honor of the McNulty family of Baltimore, who's efforts played a key role in focusing fund raising and research serving the developmental disabilities community through Civitan International and the Civitan Chesapeake District Foundation.
In 2014-15 the UAB Civitan International Research Center (CIRC) will continue to be a major contributor to new research on treatments and causes of rare diseases which affect children. As one of 22 consortia working with 98 patient advocacy groups, physician scientists at UAB, including CIRC Medical Director Dr. Alan K. Percy, will play a key role in translating new research to benefit children and families challenged by devastating disorders such as Rett syndrome. NIH has provided $29-million in 2014 to expand the Rare Disease Clinical Research Network.

Dr. Alan Percy sees a young patient in the UAB Rett Syndrome Clinic located on the 1st floor of the UAB Civitan Center.Dr. Alan Percy sees a young patient in the UAB Rett Syndrome Clinic located on the 1st floor of the UAB Civitan Center.UAB is involved with clinical research in two different projects. The first deals with three disorders of the nervous system: Rett syndrome, MECP2 duplication disorder and RTT-related disorders, under the direction of Alan Percy, M.D., CIRC Medical Director. These conditions strike previously healthy-seeming children — usually girls for RTT and boys for MECP2 duplication disorder — early in their lives and can lead to seizures, difficulty with fine motor control and walking, and intellectual disability. This project, which has been funded by NIH since 2003, is preparing to launch clinical trials in the coming months.

In the second project, UAB will be part of a 10-member group of medical centers headed by Boston Children’s Hospital in studying three rare genetic syndromes, tuberous sclerosis complex, Phelan-McDermid syndrome and PTEN hamartoma tumor syndrome, which often cause autism spectrum disorder and intellectual disability. Martina Bebin, M.D., professor of neurology, is the lead investigator at UAB for the $6 million, five-year study. The ultimate goal is to launch clinical trials of new treatments and develop biomarkers that can be used to monitor treatment effectiveness for the three rare syndromes, and possibly for broader groups of ASD/ID patients.

The Rare Diseases Clinical Research Network’s efforts take the form of a natural history study with three major goals: identify and understand the core clinical features of each disorder, identify factors that can modify the severity of the disorders, and understand the relationship between patients’ symptoms and their brain imaging and electroencephalography alterations.

The 2014-2015 Civitan Emerging Scholar Awards and Civitan McNulty Scientist were announced at the Fall Civitan Board reception on November 6, 2014 in the Civitan International Research Center Atrium.

Receiving Emerging Scholar awards were: Andrew Arrant, Ph.D., Postdoctoral Fellow, Department of Neurology; Vladimir Grubisic, M.D., Ph.D., Postdoctoral Fellow, Department of Neurobiology; and Natasha Pacheco, Graduate Student Trainee, Department of Cell, Developmental and Integrative Biology. Haley Johnson, Graduate Student Trainee, Department of Psychology, is the 2014 recipient of the Whit Mallory Research Fellow Award.

Receiving UAB Civitan Emerging Scholar Awards for 2014-2015 are (r-l) Natasha Pacheco, Andrew Arrant, Haley Johnson, and Vladimir Grusbisic. Receiving UAB Civitan Emerging Scholar Awards for 2014-2015 are (r-l) Natasha Pacheco, Andrew Arrant, Haley Johnson, and Vladimir Grubisic. Andrew Arrant’s research focuses on Neuronal ceroid lipofuscinosis (NCL), a devastating neurodegenerative disorder with an age of onset ranging from infancy to early adulthood, resulting in vision loss, seizures, early-onset dementia, and early death. Potential gene therapies to target this disorder are being studied through this project. Andrew is a postdoctoral fellow in the laboratory of Dr. Erik Roberson.

Vladimir Grubisic is completing a postdoctoral fellowship in the laboratory of Vladimir Parpura. He is investigating the role of the enteric nervous system (ENS), often regarded as “the second brain” due to its size, complexity and autonomy, in gastrointestinal (GI) disturbances in mouse models of Rett and Pitt-Hopkins syndromes. GI disturbances are the most common non-neurological symptoms in RTT and PTHS patients. This research could yield new models to study RTT/PTHS-related GI disturbances, and allow the development of new therapeutic vistas to improve the quality of life of patients affected with these disorders.

Natasha Pacheco’s primary project in the laboratory focuses on abnormal astrocyte development in Rett syndrome. Working with Dr. Michelle Olsen, Natasha’s project will provide insight on the role of astrocytes in normal brain development and may illuminate how the loss of MeCP2 function in astrocytes contributes to abnormal brain development in Rett syndrome.

Haley Johnson’s research project title is “Understanding and Preventing Motor Vehicle Crashes around Social and Non-social Hazards Among Adolescent Drivers with Autism Spectrum Disorders.” Compared to nearly three-fourths of the general population, only 24% of adults with Autism Spectrum Disorder (ASD) consider themselves independent drivers. The proposed study seeks to better understand the behavioral impairments that may increase rates of unintentional injury in this vulnerable population of drivers; more specifically, to evaluate the perception of social and non-social driving hazards in ASD drivers in a simulated, driving environment. Haley is a graduate student in the laboratory of Dr. Despina Stavrinos.

Each Emerging Scholar and Whit Mallory Research Fellow receives a $25,000 award provided through support from Civitan International. This program provides direct funding to advanced graduate students and postdoctoral fellows in their research efforts to address the causes and treatments of developmental disabilities.