Scientists have discovered a defect in the cells of autism sufferers – and there are already two approved medications to combat it.
In 50 per cent of cases, autism stems from a genetic disorder called tuberous sclerosis complex (TSC).
Despite years of studies geared towards targeting TSC, it remains incurable.
However, new research by the Boston Children’s Hospital suggests this condition could be caused by a defect in the way cells recycle their mitochondria (the cell’s ‘battery’).
The scientists further showed that two existing classes of drugs counter the defect: the epilepsy drug carbamazepine, and drugs known as mTOR inhibitors.
Two medications – including epilepsy pills carbamazepine – treat the autophagy defect that scientists believe could be at the root of autism, paving the way for new treatments
When treated, the dysfunctional neurons were able to clear damaged mitochondria and replenish healthy mitochondria, restoring a normal turnover.
The scientists believe the study, published by Cell Reports, open new treatment possibilities not just for TSC, but for other forms of autism and neurologic disorders.
‘Our findings point to possible treatments for enhancing mitophagy for some neurodevelopmental and neurodegenerative diseases,’ says lead researcher Dr Mustafa Sahin, director of the Translational Neuroscience Center at Boston Children’s Hospital.
Mitochondria constantly get recycled.
Through a process known as autophagy (‘self-eating’), cells digest their damaged or aging mitochondria, clearing the way for healthy replacements.
It was research into this procedure – autophagy – that earned a Nobel Prize this year.
But as Dr Sahin showed with co-first authors Dr Darius Ebrahimi-Fakhari and medical student Afshin Saffari, autophagy does not happen as it should do in many autism sufferers.
It is not the first time scientists have analyzed autophagy in patients with neurological diseases.
Research has shown issues with autophagy in people with Parkinson’s disease and Alzheimer’s disease.
But this is the first study that connects autism sufferers to the same defect.
Dr Sahin said it has taken this long to reach this point because the autism population is diverse and hard to define.
‘We decided to use tuberous sclerosis, a genetically defined disorder that has a high incidence of autism, as a model to understand the role of mitochondrial dynamics,’ Dr Sahin explained.
To reach their conclusion, the team studied rat neurons and patient-derived neurons affected by TSC.
New research by the Boston Children’s Hospital suggests this condition could be caused by a defect in the way cells recycle their mitochondria (the cell’s ‘battery’)
They then used live-cell imaging to examine the mitochondria.
They found that the TSC neurons as a whole had more mitochondria – even fragmented and dysfunctional mitochondria that should have been recycled.
COULD AVAILABLE MEDICATIONS TREAT AUTISM?
The researchers were able to restore normal mitophagy and replenish functioning mitochondria – in both neurons in a dish and in live mice.
They did this surgically – by inserting a healthy version of mutated genes.
But they also used rapamycin (an mTOR inhibitor) and carbamazepine (anti-seizure medication).
Both had the same effect.
The team said more work is needed to study the interaction between these medications and TSC to see how it could be used on a broader scale.
‘Our work defines mitochondrial homeostasis as a therapeutic target for TSC, and may also have implications for other neurological diseases that involve mitochondrial dysfunction,’ Dr Ebrahimi-Fakhari said.