Breaking News
December 14, 2018 - New model could cure the potential to underestimate how quickly diseases spread
December 14, 2018 - Exercise-induced hormone activates cells critical for bone remodeling in mice
December 14, 2018 - Researchers discover new mechanism behind spread of malignant pleural mesothelioma
December 14, 2018 - Health Tip: Celebrate a Healthier Holiday
December 14, 2018 - Scalpel-free surgery enhances quality of life for Parkinson’s patients, study finds
December 14, 2018 - Early physical therapy can reduce risk, amount of long-term opioid use | News Center
December 14, 2018 - Genetic marker, predictor of early relapse in common childhood cancer discovered
December 14, 2018 - Study could lead to a potential new way of treating sepsis
December 14, 2018 - New protein complex helps embryonic stem cells to maintain their indefinite potential
December 14, 2018 - Salk professor receives $1.8 million from NOMIS Foundation for research on mechanisms to promote health
December 14, 2018 - New discovery will improve the safety and predictability of CRISPR
December 14, 2018 - Geneticists discover how sex-linked disorders arise
December 14, 2018 - New method to visualize small-molecule interactions inside cells
December 14, 2018 - Study describes mechanism that makes people more vulnerable to hunger-causing stimuli
December 14, 2018 - Chronic opioid therapy associated with increased healthcare spending and hospital stays
December 14, 2018 - Blood Types
December 14, 2018 - Obesity linked to increased risk of early-onset colorectal cancer
December 14, 2018 - Blood test helps identify distinct molecular signatures in children with cystic fibrosis
December 14, 2018 - Scientists use water to track electrical activity of nerve cells
December 14, 2018 - Recurrence of urinary tract infection may depend on bacterial strain, study shows
December 14, 2018 - GBT Announces U.S. FDA Agrees with its Proposal Relating to Accelerated Approval Pathway for Voxelotor for the Treatment of Sickle Cell Disease and GBT Plans to Submit New Drug Application (NDA)
December 14, 2018 - Partial Thromboplastin Time (PTT) Test: MedlinePlus Lab Test Information
December 14, 2018 - Common tactics for health promotion at work may be detrimental to employees with obesity
December 14, 2018 - Myths about migration and health not supported by available evidence
December 14, 2018 - Recent findings on rare genetic disorder may help develop new treatment options
December 14, 2018 - New drug shows promise in treating sarcomas
December 14, 2018 - Scientists perform lung lavage as new approach for tuberculosis diagnosis in rhinoceros
December 14, 2018 - Recent winners of the Nobel Medicine Prize
December 14, 2018 - KHN’s ‘What the Health?’ Insurance enrollment is lagging — and there are lots of reasons why
December 14, 2018 - Study assesses safety and efficacy of new treatment for pancreatic cancer
December 14, 2018 - Study finds drug targets for Ebola, Dengue, and Zika viruses
December 14, 2018 - Shining new light on neuron firing
December 14, 2018 - Study highlights need for personalized approach to treat ICU acquired delirium
December 14, 2018 - Soot particles from road traffic significantly contribute to air pollution
December 14, 2018 - Massage helps relieve pain, improve mobility in patients with knee osteoarthritis
December 14, 2018 - Researchers explore home healthcare nurses’ knowledge attitudes toward infection control
December 14, 2018 - Average outpatient visit in the U.S. costs nearly $500, shows new study
December 14, 2018 - Reference Infliximab, Biosimilar Equivalent for Crohn’s Disease
December 14, 2018 - New contact lens to treat eye injuries
December 14, 2018 - Acne could have a genetic basis find researchers promising new cure
December 14, 2018 - Higher physical activity associated with improved mood
December 14, 2018 - New UGA study points to optimal hypertension treatment for stroke patients
December 14, 2018 - Study highlights factors that can reduce food cravings
December 14, 2018 - Researchers discover Ebola-fighting protein in human cells
December 14, 2018 - Fentanyl surpasses heroin in cause of U.S. drug overdose deaths
December 14, 2018 - When Heart Attack Strikes, Women Often Hesitate to Call for Help
December 14, 2018 - A warning about costume contacts
December 14, 2018 - Study examines link between peripheral artery disease and heart attack
December 14, 2018 - Researchers develop biotechnological tool to produce antifungal proteins in plants
December 14, 2018 - 3D-printed adaptive aids can benefit patients with arthritis
December 14, 2018 - Chronic bullying during adolescence impacts mental health
December 14, 2018 - Integral Molecular and Merus collaborate to develop bispecific antibody therapeutics
December 13, 2018 - Importance of cell cycle and cellular senescence in the placenta discovered
December 13, 2018 - Gold “nanoprisms” open new window into vessels and single cells
December 13, 2018 - Research findings could lead to new targets for cancer-fighting therapeutics
December 13, 2018 - Butantan Institute signs collaboration agreement with MSD to develop dengue vaccines
December 13, 2018 - Study explores how patients want to discuss symptoms with doctors
December 13, 2018 - RUDN medics first to gather scattered data on hepatitis morbidity in Somalia
December 13, 2018 - Age and gender disparities found in use of bed nets to prevent malaria in sub-Saharan Africa
December 13, 2018 - Caffeine therapy benefits developing brains of premature babies
December 13, 2018 - New review focuses on electrospinning techniques used in musculoskeletal tissue engineering
December 13, 2018 - A new division focused on human immune system
December 13, 2018 - Zogenix Announces Positive Phase 3 Trial Results on the Efficacy and Safety of Fintepla (ZX008) in Dravet Syndrome
December 13, 2018 - BCR ABL Genetic Test: MedlinePlus Lab Test Information
December 13, 2018 - Caffeinated beverages during pregnancy linked to lower birth weight babies
December 13, 2018 - Stanford Medicine Health Trends Report examines opportunity to democratize health care
December 13, 2018 - Obsessive-compulsive disorder may protect individuals from obesity
December 13, 2018 - Scientists investigate how a painful event is processed in the brain
December 13, 2018 - Genetic study reveals new insights into underlying causes of moderate-to-severe asthma
December 13, 2018 - Study uncovers new genetic clues to frontotemporal dementia
December 13, 2018 - Vitamin C supplementation for pregnant smokers may reduce harm to infants’ lungs
December 13, 2018 - New study reveals yin-yang personality of dopamine
December 13, 2018 - Research identifies nerve-signaling pathway behind sustained pain after injury
December 13, 2018 - Children with high levels of callous traits show widespread differences in brain structure
December 13, 2018 - Long-term Benefit of Steroid Injections for Knee Osteoarthritis Challenged
December 13, 2018 - Adding new channels to the brain remote control
December 13, 2018 - In the Spotlight: A different side of neuroscience
December 13, 2018 - Medical Marvels: Using immunotherapy for melanoma that spread to the brain
December 13, 2018 - Puzzles do not keep dementia away finds study
December 13, 2018 - New mouse model shows potential for rapid identification of promising muscular dystrophy therapies
Drug treatment at a young age could help reverse autism-like behavior in tuberous sclerosis

Drug treatment at a young age could help reverse autism-like behavior in tuberous sclerosis

image_pdfDownload PDFimage_print

New research on autism has found, in a mouse model, that drug treatment at a young age can reverse social impairments. But the same intervention was not effective at an older age.

The study is the first to shed light on the crucial timing of therapy to improve social impairments in a condition associated with autism spectrum disorder. The paper, from Boston Children’s Hospital, the University of Texas, Harvard Medical School and Toronto’s Hospital for Sick Children, was published today in Cell Reports.

Tuberous sclerosis and autism

Many of the hundreds of genes that likely regulate complex cognitive and neuropsychiatric behaviors in people with autism still remain a mystery. However, genetic disorders such as tuberous sclerosis complex, or TSC, are providing clues. Patients often have mutations in the TSC1 or TSC2 gene, and about half develop autism spectrum disorder.

The investigators, led by Peter Tsai, MD, PhD, at UT Southwestern Medical Center, used a mouse model in which the TSC1 gene is deleted in a region of the brain called the cerebellum.

“There were several mouse models of TSC previously published, but they all had seizures and died early in life, making it difficult to study social cognition,” says Mustafa Sahin, MD, PhD, who directs the Translational Neuroscience Center and the Translational Research Program at Boston Children’s and was the study’s senior investigator. “That is one reason why we turned to knocking out the TSC1 gene only in cerebellar Purkinje cells, which have been implicated in autism. These mice have normal lifespans and do not develop seizures.”

Timing is everything

The new research fed off a previous study published in 2012. In that study, Sahin and colleagues treated the mutant mice starting in the first week of life with rapamycin, a drug approved by the FDA for brain tumors, kidney tumors and refractory epilepsy associated with TSC. They found that they could rescue both social deficits and repetitive behaviors.

But when a similar drug, everolimus, was tested in children with TSC, neurocognitive functioning and behavior didn’t significantly improve. Sahin and his colleagues wondered whether there was a specific developmental period during which treatment would be effective.

The new mouse study delineates not only the timeframe for effective rapamycin treatment of certain autism-relevant behaviors, but also some of the cellular, electrophysiological and anatomic mechanisms for these sensitive periods.

“We found that treatment initiated in young adulthood, at 6 weeks, rescued social behaviors, but not repetitive behaviors or cognitive inflexibility,” says Sahin.

More importantly, neither the social deficits nor the repetitive behaviors responded when the treatment was started at 10 weeks.

Using advanced imaging, the researchers went on to show that the rescue of social behaviors correlates with reversal of specific MRI-based structural changes, cellular pathology and Purkinje cell excitability. Meanwhile, motor learning rescue appeared independent of Purkinje cell survival or rescue of cellular excitability.

A new clinical trial?

Based on the mouse findings, Sahin is now seeking funds to test whether early treatment can improve a broad range of autistic-like behaviors in children with TSC. Specifically, he’ll explore whether treatment as early as 12 to 24 months can help prevent both social deficits and repetitive inflexible behaviors. He hopes to see better results than in the earlier clinical trial, which involved children ages 6 to 21.

Past research indicates that different autism-related disorders may have different windows of treatment. For example, animal studies of Rett syndrome suggest that treatment can be effective relatively late in life and still improve neurological outcome.

Source:

https://vector.childrenshospital.org/2018/10/rapamycin-autism-tuberous-sclerosis/

Tagged with:

About author

Related Articles